VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE D - CORE

ALGORITHM AND ANNOTATIONS

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MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**Module D - Core**

SUMMARY

This core module provides an overview of the important components of
diabetes care that should be considered at each visit, and performed at
appropriate intervals. Its objective is to assist the provider with the
organization and prioritization of a care plan for persons with diabetes
mellitus (DM).

ANNOTATIONS

# Patient with Diabetes Mellitus

DEFINITION

Diabetes mellitus is a state of absolute or relative insulin deficiency
resulting in hyperglycemia. This algorithm applies to adults only (age ≥
18), both type 1 and type 2 (formerly referred to as insulin-dependent
and non-insulin dependent diabetes mellitus) but not to gestational
diabetes mellitus (GDM).

BIOCHEMICAL CRITERIA FOR DIAGNOSIS

The criterion for the diagnosis of DM is either two fasting blood sugar
readings with results ≥ 126 mg/dL or two random blood sugars with values
≥ 200 mg/dL, if symptoms of DM are present.

Oral glucose tolerance testing is no longer recommended in clinical
practice. Hemoglobin A~1~c (HbA~1~c) measurement is not recommended as a
screening test. An individual with a casual plasma glucose level ≥ 200
mg/dL but without symptoms should have his or her fasting blood glucose
measured.

Individuals with impaired glucose homeostasis have an increased risk of
developing DM and should receive counseling regarding weight control,
exercise, and future screening.

#### Table D1. Diagnosis of Diabetes Mellitus

+-----------------------+-----------------------+----------------------+
| # Status              | **Fasting Plasma      | **Casual Plasma      |
|                       | Glucose**             | Glucose**(c)         |
|                       |                       |                      |
|                       | **(FPG) Preferred     |                      |
|                       | Level** (a), (b)      |                      |
+-----------------------+-----------------------+----------------------+
| Diabetes mellitus     | FPG \> 126 mg/dL (7.0 | Casual plasma        |
|                       | mmol/L)               | glucose ≥ 200 mg/dL  |
|                       |                       | (11.1 mmol/L) plus   |
|                       |                       | symptoms             |
+-----------------------+-----------------------+----------------------+
| Impaired glucose      | Impaired fasting      |                      |
| homeostasis           | glucose (IFG)\        |                      |
|                       | FPG ≥ 110; \< 126     |                      |
|                       | mg/dL                 |                      |
+-----------------------+-----------------------+----------------------+
| Normal                | FPG \< 110 mg/dL      |                      |
+-----------------------+-----------------------+----------------------+

(a) Fasting is defined as no caloric intake for at least 8 hours.

(b) FPG is the preferred test for diagnosis, but either of the two
    listed is acceptable. In the absence of unequivocal hyperglycemia
    with acute metabolic decompensation, one of these two tests should
    be used on a different day to confirm the diagnosis.

(c) Casual means any time of day without regard to time since last meal;
    classic symptoms include polyuria, polydipsia, and unexplained
    weight loss.

DISCUSSION

Patients with one or more of the following risk factors have a higher
risk to be diagnosed with diabetes:

-   Age ≥ 45 years

-   Family history (parents or siblings with DM)

-   High-density lipoprotein cholesterol (HDL-C) level ≤ 35 mg/dL (0.90
    mmol/L) and triglyceride (TG) level ≥ 250 mg/dL (2.82 mmol/L)

-   History of gestational diabetes mellitus (GDM); or women delivering
    babies weighing \> 9 pounds

-   Hypertension (blood pressure ≥ 140/90 mmHg)

-   Obesity (≥ 20 percent above ideal body weight, or body mass index
    (BMI) ≥ 27 kg/m^2^)

-   History of impaired fasting glucose (IFG) or impaired glucose
    tolerance (IGT)

-   Race/ethnicity---African American, Hispanic American, Native
    American, Asian American, Pacific Islander.

*Major risk factors for DM*: adapted from ADA 1999

# Refer to Pediatric Diabetes Management

OBJECTIVE

To provide appropriate management for diabetic children.

ANNOTATION

Approximately three-fourths of all newly diagnosed cases of type 1 DM
occur in children (below the age of 18). Children's health care needs
are different from those of adults in several ways. Providing health
care to children not only must involve meeting their physical needs but
must address their changing developmental stages. It is important to
remember that young children have a limited ability to communicate their
needs and to indicate if they are in pain and therefore should not be
expected to understand specific clinical interactions.

Primary care providers should refer children with diabetes for
consultative care to a team with expertise in providing care to
children. Members of this team must have knowledge of and experience in
meeting the medical, psychosocial, and developmental needs of children.
The pediatric diabetic team should comprise at a minimum, a
pediatrician, a certified diabetes educator, a registered nurse, a
registered dietitian, and a social worker, all with expertise and
specialized training in the comprehensive care of the child with
diabetes.  

# Is Patient a Female of Reproductive Potential?

OBJECTIVE

To assess the risk of maternal fetal complications should unintended
pregnancy occur and to implement prevention strategies.

ANNOTATION

Primary care providers should strongly recommend to all patients with
pre-existing diabetes that they plan for and prepare for each pregnancy.
Primary care providers should also counsel all diabetic female patients
of reproductive potential on the need for optimal glycemic control.

Because of the high risk nature of the diabetic pregnancy and the need
for intensive multidisciplinary monitoring and patient support, referral
of diabetic patients to an expert high risk perinatal team at the
earliest possible opportunity must be considered as the standard of
care. Ideally, such referral should be made during the period of planned
conception.

DISCUSSION

The risk of fetal congenital anomalies is directly related to the
periconceptual HbA~1~c values. The major determinant of outcome is the
degree of maternal glycemic control in the preconceptual,
periconceptual, and gestational periods.

Nondiabetic pregnancies with maternal HbA~1~c levels below 7.0 mg/dL
translate into a 1 to 2 percent risk of fetal anomalies; for diabetic
pregnancies, maternal levels of HbA~1~c above 11 percent result in
anomalies in 25 percent of these pregnancies.

Abnormalities related to deficient control of maternal diabetes are:

-   Congenital anomalies: overall risk of 13 to 18 percent

-   Central nervous system (CNS) anomalies: 8.5 percent

-   Cardiac anomalies: 5.3 percent.

Fetal complications of maternal hyperglycemia, besides congenital
malformations, include:

-   Macrosomia

-   Neonatal delivery-related trauma

-   Neonatal hypoglycemia

-   Stillbirth.

Maternal complications that occur at above average rate in diabetic
pregnancies include:

-   Preeclampsia

-   Hypertension

-   Preterm labor

-   Need for cesarean section.

In addition to providing intensive glycemic control, the primary care
provider should:

-   Prescribe supplemental folic acid and a dietetic regimen to ensure
    appropriate caloric intake during pregnancy

-   Screen for autoimmune thyroid disease, hypertension, and renal
    disease.

EVIDENCE

Becerra et al., 1990. SR = IIb, LE = B; Lucas 1989. SR = I, LE = B;
Miller 1981. SR = I, LE = B; Fuhrmann et al., 1983. SR = I, LE = B;
Cousins 1987. SR = IIa, LE = B

# Identify Comorbid Conditions

OBJECTIVE

To evaluate DM management in the context of the patient\'s total health
status.

ANNOTATION

DM may not be the patient\'s only disease, nor is it necessarily the
condition that needs to be prioritized for immediate treatment. Persons
with DM are at risk of multiple comorbid conditions including:

-   Coronary artery disease (CAD)

-   Peripheral vascular disease (PVD)

-   Hypertension (HTN)

-   Hyperlipidemia.

The following are examples of conditions that affect the management of
DM:

-   Chronic obstructive pulmonary disease (COPD)

-   Substance use disorder (SUD)

-   Depression.

Among the more frequently encountered precipitating factors resulting in
secondary diabetes are:

-   Pancreatic disease (e.g., due to alcoholism, pancreatic
    insufficiency secondary to chronic pancreatitis, malignancy,
    hemochromatosis)

-   Drug induced disease (especially thiazide diuretics, steroids,
    phenytoin).

# Is the Patient Medically, Psychologically, and Socially Stable?

OBJECTIVE

To stabilize the patient before initiating long-term disease management.

ANNOTATION

-   Urgent or semiurgent medical conditions, including hypo- or
    hyperglycemia, must be treated before long-term disease management
    principles are applied

-   The urgency of medical treatment, including the necessity for
    hospitalization, will depend upon the presence of ketoacidosis,
    dehydration, hyperosmolarity, infections, etc.

-   Psychiatric illness and marked socioeconomic hardship (homelessness,
    absence of support system, unemployment, absence of reliable
    transportation, etc.) pose significant barriers to diabetic
    management. If such circumstances are identified, involvement of
    mental health, social services, and case management professionals
    may enhance patient compliance with treatment and follow-up.

-   Stable condition represents the judgment of the provider.

# Identify/Update Related DM Problems from the Medical Record, History, Physical Examination, Laboratory Tests, Nutritional and Educational Assessment

OBJECTIVE

To obtain and document a complete medical evaluation for the patient
with DM annually.

ANNOTATION

In addition to a general medical examination, a complete evaluation of
patients with DM will include:

-   Information regarding the onset and duration of DM

-   The history of hospitalization for diabetic events

-   A review of glycemic control

-   Measurement of serum lipids

-   Identification of foot complications

-   Identification of eye complications

-   Screening for hypertension

-   Screening for renal disease

-   Identification of macrovascular disease

-   Identification of neurovascular disease

-   Assessment of psychosocial status (including family support)

-   Appraisal of self-management skills.

On a follow-up visit, the evaluation should focus on updating of new
information and/or changes to the patient record. The components of
evaluation are summarized in Table D2.

#### Table D2. Evaluation of the Diabetic Patient

+-----------+-----------------------+-----------------+---------------+
| **E       | ## H                  | **Physical      | *             |
| valuation | istory-Patient/Family | Examination**   | *Laboratory** |
| Co        |                       |                 |               |
| mponent** |                       |                 |               |
+===========+=======================+=================+===============+
| #         | -   Home glucose      | -   Weight      | -   HbA~1~c   |
|  Glycemia |     monitoring        |                 |               |
|           |     records           | -   Height      | -   Fasting   |
|           |                       |                 |     glucose   |
|           | -   Hyperglycemia     | -   Body mass   |               |
|           |                       |     index (BMI) |               |
|           | -   Ketoacidosis      |                 |               |
|           |                       | > is calculated |               |
|           | -   Hypoglycemia      | > by dividing   |               |
|           |                       | > the patient's |               |
|           | -   Lifestyle         | > weight in kg  |               |
|           |                       | > by the        |               |
|           | -   Nutrition         | > patient's     |               |
|           |                       | > height, in    |               |
|           | -   Current and past  | > meters        |               |
|           |     medications       | > squared.      |               |
|           |                       |                 |               |
|           | Also consider         |                 |               |
|           | secondary etiologies: |                 |               |
|           |                       |                 |               |
|           | -   Cushing's disease |                 |               |
|           |                       |                 |               |
|           | -   Acromegaly        |                 |               |
|           |                       |                 |               |
|           | -   Hemochromatosis   |                 |               |
|           |                       |                 |               |
|           | -   Medications       |                 |               |
+-----------+-----------------------+-----------------+---------------+
| # Foot    | Symptoms of           | Visual          | N/A           |
|           | neuropathy---pain,    | inspection      |               |
|           | paresthesia           | including:      |               |
|           |                       |                 |               |
|           | Symptoms of           | -   Nails       |               |
|           | peripheral vascular   |                 |               |
|           | disease               | -   Web spaces  |               |
|           |                       |                 |               |
|           | Symptoms of systemic  | -   Ulcers      |               |
|           | or local infection    |                 |               |
|           |                       | -   Calluses    |               |
|           | Previous episodes of  |                 |               |
|           | foot complications:   | -   Deformities |               |
|           |                       |                 |               |
|           | -   Foot deformity    | Palpation of    |               |
|           |                       | pulses and      |               |
|           | -   Skin breakdown    | determination   |               |
|           |                       | of              |               |
|           | -   Ulcers            | sensa           |               |
|           |                       | tion---consider |               |
|           | -   Amputations       | using a 5.07    |               |
|           |                       | monofilament    |               |
+-----------+-----------------------+-----------------+---------------+
| ### Eye   | -   Changes in vision | Visual acuity,  | N/A           |
|           |                       | if changes in   |               |
|           | -   Laser treatment   | vision are      |               |
|           |                       | reported        |               |
|           | -   Glaucoma          |                 |               |
|           |                       |                 |               |
|           | -   Dilated retinal   |                 |               |
|           |     exam by eye care  |                 |               |
|           |     provider within   |                 |               |
|           |     last year         |                 |               |
+-----------+-----------------------+-----------------+---------------+

**Table D2. Evaluation of the Diabetic Patient (Continued)**

+-----------+-----------------------+-----------------+---------------+
| **E       | ## H                  | **Physical      | *             |
| valuation | istory-Patient/Family | Examination**   | *Laboratory** |
| Co        |                       |                 |               |
| mponent** |                       |                 |               |
+===========+=======================+=================+===============+
| Kidney    | -   Known history of  | Edema           | -   Routine   |
|           |     diabetic disease  |                 |               |
|           |                       |                 |    urinalysis |
|           | -   Family history of |                 |               |
|           |     hypertension and  |                 | -   Test for  |
|           |     renal disease     |                 |     micr      |
|           |                       |                 | o-albuminuria |
|           |                       |                 |     and serum |
|           |                       |                 |               |
|           |                       |                 |    creatinine |
|           |                       |                 |     level if  |
|           |                       |                 |               |
|           |                       |                 |    indicated, |
+-----------+-----------------------+-----------------+---------------+
| ### Hyp   | -   Previous          | Blood pressure  | N/A           |
| ertension |     diagnosis of      |                 |               |
|           |     hypertension      |                 |               |
|           |                       |                 |               |
|           | -   Current and       |                 |               |
|           |     previous          |                 |               |
|           |     medications       |                 |               |
+-----------+-----------------------+-----------------+---------------+
| Coronary  | Atherosclerotic       | Cardiac         | -   EKG       |
| and       | disease:              | examination:    |               |
| P         |                       |                 | -   Fasting   |
| eripheral | -   Myocardial        | -   Heart       |     lipid     |
| Arterial  |     infarction        |                 |     profile   |
| Disease/  |     (MI)/angina       | -   Peripheral  |     if not    |
|           |                       |     circulation |     done      |
| Hyper     | -   Stroke            |     including   |     within    |
| lipidemia |                       |     pulses and  |     last year |
|           | -   Transient         |     bruits      |               |
|           |     ischemic attack   |                 |               |
|           |     (TIA)             | -   Cutaneous   |               |
|           |                       |     or          |               |
|           | -   Claudication      |     tendinous   |               |
|           |                       |     xanthomata  |               |
|           | -   Surgical history  |                 |               |
|           |     of                |                 |               |
|           |     revascularization |                 |               |
|           |                       |                 |               |
|           | Atherosclerotic risks |                 |               |
|           | other than diabetes:  |                 |               |
|           |                       |                 |               |
|           | -   Smoking history   |                 |               |
|           |                       |                 |               |
|           | -   Family history    |                 |               |
|           |                       |                 |               |
|           | -   Previous          |                 |               |
|           |     diagnosis of      |                 |               |
|           |     hyperlipidemia;   |                 |               |
|           |     triglycerides     |                 |               |
|           |                       |                 |               |
|           | Current and previous  |                 |               |
|           | medications:          |                 |               |
|           |                       |                 |               |
|           | -   Aspirin           |                 |               |
|           |                       |                 |               |
|           | -   Estrogen therapy  |                 |               |
|           |                       |                 |               |
|           | -   Hypolipidemics    |                 |               |
+-----------+-----------------------+-----------------+---------------+
| Neur      | Sensory state of:     | -               | N/A           |
| ovascular |                       |    Interosseous |               |
|           | -   Hands and feet    |     muscle      |               |
|           |                       |     wasting     |               |
|           |                       |                 |               |
|           |                       | -   Deep tendon |               |
|           |                       |     reflexes    |               |
+-----------+-----------------------+-----------------+---------------+
| Self-     | Knowledge,            | Observation:    | N/A           |
| m         | understanding and     |                 |               |
| anagement | self -described       | -   Home        |               |
| education | behaviors of :        |     glucose     |               |
|           |                       |     monitoring  |               |
|           | -   Use of medication |     if          |               |
|           |                       |     indicated   |               |
|           | -   Goals of          |                 |               |
|           |     treatment         | -   Foot        |               |
|           |                       |     s           |               |
|           | -   Diet and self     | elf-examination |               |
|           |     management skills |                 |               |
|           |                       |                 |               |
|           | -   What to do in     |                 |               |
|           |     case of           |                 |               |
|           |     complications     |                 |               |
+-----------+-----------------------+-----------------+---------------+
| Other     | -   Dental history    | -   Oral        | N/A           |
|           |     and oral exam     |     examination |               |
|           |                       |                 |               |
|           | -   Dental and        |                 |               |
|           |     gingival health   |                 |               |
+-----------+-----------------------+-----------------+---------------+
|           | -   Infections        | N/A             |               |
|           |                       |                 |               |
|           | -   Insulin injection |                 |               |
|           |     sites             |                 |               |
|           |                       |                 |               |
|           | -   Immunizations:    |                 |               |
|           |     flu, pneumovax    |                 |               |
+-----------+-----------------------+-----------------+---------------+

EDUCATIONAL ASSESSMENT

Expert opinion led to development of the following questions that are
believed to reflect the patient's general knowledge and ability to
self-manage his or her diabetes adequately.

-   Is there anything you do or have been advised to do because of your
    diabetes that you have difficulty with or are unable to do?

-   Do you know what to do when your sugar is high/low (describe both
    hyperglycemia and hypoglycemia symptoms)? Who and when do you call?

-   Do you remember your target goals: HbA~1~c, low-density lipoprotein
    (LDL), weight, exercise, blood pressure?

-   Which food affects your blood sugar the most---chicken breast,
    salad, or potato?

Inability of the patient to answer these questions indicates possible
deficiency in knowledge and self-management skills. The clinician can
refer to Module M (Self-Management/Education) for additional assessment
and action plans.

Patients with DM who have more immediate medical or psychiatric problems
should still have an educational need assessment done. This evaluation
is to determine whether they have sufficient skills to manage their
glycemic control during a period of concurrent illness, with a goal of
avoiding symptomatic hypo- or hyperglycemia.

# Determine and Document if Diabetes Mellitus is Type 1 or 2 

OBJECTIVE

To determine what treatment components are needed for a particular
patient.

ANNOTATION

Patients with type 1 DM are insulinopenic (virtually absent insulin
secretion), often due to autoimmune or toxic (e.g., alcohol) destruction
of the pancreatic beta cells. Patients with type 2 DM have underlying
insulin resistance and relative insulin deficiency.

In a primary care setting, determination of the patient\'s age at the
diagnosis of DM, plus BMI, and level of urinary ketones, is usually
sufficient to classify the patient.

#### Table D3. Clinical Classification of DM

+----------------+-----------------+----------------+-----------------+
|                | **Likely Type   | **I            | ###             |
|                | 1**             | ndeterminate** | # Likely Type 2 |
+----------------+-----------------+----------------+-----------------+
| # Age          | \< 30  years    | 30 - 40  years | \> 40  years    |
+----------------+-----------------+----------------+-----------------+
| **BMI**        | \< 25  BMI      | 25 - 27        | \> 27           |
+----------------+-----------------+----------------+-----------------+
| # U            | Moderate to     | Low to         | None to low     |
| rinary ketones | large           | moderate       |                 |
+----------------+-----------------+----------------+-----------------+

DISCUSSION

Because patients with type 2 or initially indeterminate DM can present
with ketoacidosis (especially with concomitant alcohol use), the patient
should be reevaluated after stabilization to assess continued need for
insulin therapy.

CLINICAL CLASSIFICATION OF TYPE 1 OR 2

Patients with type 1 DM require insulin and will develop ketoacidosis if
not treated with insulin or if insulin requirement increases during
stress. Patients with type 1 DM are generally more prone to develop
hypoglycemia or ketosis, especially during times of stress.

Patients with type 2 DM may need to be treated with insulin to improve
glycemic control but will usually not develop ketoacidosis if they do
not receive insulin. Patients with DM adequately treated with medical
nutritional therapy (MNT), physical activity, and/or oral agents are
classified as having type 2 DM.

# Review Systems and Set Priorities for Patient's Care

OBJECTIVES

Identify DM related complications requiring special attention.

ANNOTATION

Diabetes is the major cause for non-traumatic amputations, end-stage
renal disease, and visual loss. In addition, the major cause of
morbidity and mortality in diabetic patients is macrovascular disease.
Effective strategies exist for preventing or treating micro- and
macrovascular complications, thereby delaying or preventing end organ
damage.

The provider and the patient must jointly negotiate the sequence and
timing of the various assessments. Further, prioritization should be
based on the risk of the individual patient for that complication.

This guideline recommend annual assessment of foot, lipid and renal
function; annual exam eye (biannual for low risk patients); measurement
of blood pressure at each office visit as well as reinforcement of life
style, nutritional and exercise as appropriate. Glycemic control is
recommended at each routine visit or any visit that relates to other
concurrent problems.

If the assessment reveals any complication in any of these risk areas,
further evaluation and management is indicated. The provider should then
follow the appropriate module.

# References for Module D

American Diabetes Association. Screening for type 2 Diabetes. Position
Statement. *Diab Care* 1999; 21(Suppl. 1);S20-22

[]{.mark}

Becerra JE; Khoury MJ; Cordero JF; Erickson JD. Diabetes mellitus during
pregnancy and the risks for specific birth defects: a population-based
case-control study. *Pediatrics* 1990 Jan; 85(1):1-9

Cousins L. Pregnancy complications among diabetic women: review
1965-1985. *Obstet Gynecol Surv* 1987 Mar; 42(3):140-49

Fuhrmann K; Reiher H; Semmler K; Fischer F; Fischer M; Glockner E.
Prevention of congenital malformations in infants of insulin-dependent
diabetic mothers. *Diab Care* 1983 May-Jun; 6(3):219-23

Lucas MJ; Leveno KJ; Williams ML; Raskin P; Whalley PJ. Early pregnancy
glycosylated hemoglobin, severity of diabetes, and fetal malformations.
*Am J Obstet Gynecol* 1989 Aug;161(2):426-31

Miller E; Hare JW; Cloherty JP; Dunn PJ; Gleason RE; Soeldner JS;
Kitzmiller JL. Elevated maternal hemoglobin A~1~c in early pregnancy and
major congenital anomalies in infants of diabetic mothers. *NEJM* 1981
May 28; 304(22):1331-34

VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE G - GLYCEMIC CONTROL

ALGORITHM AND ANNOTATIONS

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MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

Module G - Glycemic Control

# Patient with Diabetes Mellitus 

Definition

Every patient with diabetes mellitus (DM), regardless of its duration,
needs to negotiate with his or her provider an appropriate target
glycemic goal and then plan a treatment strategy to achieve this goal.

Glycemic control should be reevaluated at every regular interim visit or
in the context of visits that relate to other concurrent problems that
could affect glycemic control.

# Assess Glycemic Control 

Objective

To determine the patient's current level of glycemic control.

Annotation

Glycosylated hemoglobin measured or reported as hemoglobin HbA~1~c, is
the only laboratory test measure validated in controlled, randomized
clinical trials as a predictor of risk for microvascular complications.
Hence, periodic measurement of HbA~1~c is recommended to assess glycemic
control over time.

Discussion

Assessment of glycemic control requires an understanding of the methods
used to assess as well as their accuracy. See Appendix G1, Measurement
of Glycemic Control.

# Determine recommended Glycemic Control Target Using Risk Stratification Criteria 

OBJECTIVE

To assess the risk of the patient for developing visual loss, renal
insufficiency, and amputations.

ANNOTATION

Determination of an optimal target HbA~1~c level is based upon the risk
for developing microvascular complications. The individual risk is
dependent on life expectancy, absence or presence of pre-existing
microvascular complications, and genetic factors.

The likelihood of developing microvascular complications is largely
dependent on how high the individual's glucose level has been and for
how long. The duration of glycemic exposure, is like smoking duration
for cancer risk; the severity of hyperglycemia is like the number of
packs of cigarettes smoked daily. HbA~1~c level is the best measure of
the severity of hyperglycemia over time. The presence and stage of
microvascular complications reflects prior duration and severity of
hyperglycemic exposure, and individual susceptibility to development of
complications.

The glycemic target range must be individualized for each patient based
on the clinician's appraisal of the risk-benefit ratio for that
individual. Additionally, following counseling, the patient's own
preferences should be factored into the decision-making. The risks and
benefits of a target value must be determined mutually by both the
provider and the person with diabetes in the context of the proposed
therapeutic regimen as well as patient preferences.

In general, patients with very mild or no microvascular complications of
diabetes and those free of major concurrent illnesses adversely
affecting quality of life and survival are most apt to benefit from
intensive treatment intended to achieve near-normoglycemia. Conversely,
patients with advanced microvascular complications and/or major comorbid
illness may be less likely to show survival benefit, may continue to
show progression of microvascular disease, and frequently may be at
increased risk for severe hypoglycemic morbidity when normoglycemic
control is attempted.

In the absence of a readily available mechanism to assist the provider
in the estimation of life expectancy. Table G1 is intended to provide an
overall perspective. To aid the clinician in counseling diabetic
patients about individual glycemic control goals, the table provides a
decision making matrix that considers microvascular complications and
comorbid illness.

**Table G1. Determination of Target HbA~1~c Level**

+------------------+----------------+----------------+----------------+
| > **Major        | ########       |                |                |
| > Comorbidity**  |  Microvascular |                |                |
| > (d)            |  Complications |                |                |
| >                |                |                |                |
| > or             |                |                |                |
| >                |                |                |                |
| > **Physiologic  |                |                |                |
| > Age**          |                |                |                |
+------------------+----------------+----------------+----------------+
|                  | **Absent or    | **Moderate**   | **Advanced**   |
|                  | Mild** (a)     | (b)            | (c)            |
+------------------+----------------+----------------+----------------+
| > **Absent**     | > 7 percent    | > \< 8 percent | > \< 9 percent |
| >                | >              | >              | >              |
| > **\>** 15      | > (\< 1        | > (\< 2        | > (\< 3        |
| > years of life  | > percent      | > percent      | > percent      |
| > expectancy)    | > above upper  | > above upper  | > above upper  |
|                  | > normal       | > normal       | > normal       |
|                  | > range)       | > range)       | > range)       |
+------------------+----------------+----------------+----------------+
| > **Present**    | > \< 8 percent | > \< 8 percent | > \< 9 percent |
| > (e)            | >              | >              | >              |
| >                | > (\<2 percent | > (\<2 percent | > (\<3 percent |
| > 5 to 15 years  | > above upper  | > above upper  | > above upper  |
| > of life        | > normal       | > normal       | > normal       |
| > expectancy     | > range)       | > range)       | > range)       |
+------------------+----------------+----------------+----------------+
| > **Marked** (f) | > \< 9 percent | > \< 9 percent | > \< 9 percent |
| >                | >              | >              | >              |
| > \< 5 years of  | > (\<3 percent | > (\< 3        | > (\< 3        |
| > life           | > above upper  | > percent      | > percent      |
| > expectancy     | > normal range | > above upper  | > above upper  |
|                  |                | > normal range | > normal range |
+------------------+----------------+----------------+----------------+

(a) Mild microvascular disease is defined by early background
    retinopathy, and/or microalbuminuria and/or mild neuropathy

(b) Moderate microvascular disease is defined by pre-proliferative
    (without severe hemorrhage, intra-retinal microvascular anomalies
    (IRMA), or venous bleeding) retinopathy or persistent, fixed
    proteinuria (macroalbuminuria) and/or demonstrable peripheral
    neuropathy (sensory loss)

(c) Advanced microvascular disease is defined by severe
    non-proliferative (with severe hemorrhage, IRMA, or venous bleeding)
    or proliferative retinopathy and/or renal insufficiency (serum
    creatinine level \> 2.0 mg/dl) and/or insensate extremities or
    autonomic neuropathy (gastroparesis, impaired sweating, orthostatic
    hypotension, etc.)

(d) Major comorbidity includes, but is not limited to, any or several of
    the following conditions: cardiovascular disease, chronic
    obstructive pulmonary disease, chronic liver disease, stroke,
    malignancy

(e) Moderate degree of major comorbid condition.

(f) Severe degree or end-stage major comorbid condition.

DISCUSSION

Reduction in the incidence of microvascular complications of diabetes is
primarily a function of glycemic control (HbA~1~c level) and duration of
diabetes (life expectancy), modified by the presence of complications,
and family history. See Appendix G2, Estimating Benefit and Risk of
Glycemic Control.

Evidence

*Progression to non-proliferative retinopathy:* DCCT Research Group
1993, Strength of Recommendation (SR) = I, Level of Evidence (LE) = A;
Ohkubo et al., 1995; SR = I, LE = A; Klein et al., 1995; SR = I, LE = A

*Progression to Proliferative Retinopathy:* Klein et al., 1994; SR = I,
LE = B

*Progression to microalbuminuria:* DCCT Research Group 1993; SR = I, LE
= A; Ohkubo et al., 1995; SR = I, LE = A; Krolewski 1995; SR = I, LE =
B; Kawazu et al., 1994; SR = I, LE = A

*Progression to proteinuria:* DCCT Research Group 1993; SR = I, LE = A;
Ohkubo et al., 1995; SR = I, LE =A

*Progression to blindness:* DCCT Research Group 1993; SR = I, LE = A;
Ohkubo et al., 1995; SR = I, LE = A

*Progression to end-stage renal disease:* DCCT Research Group 1993; SR =
I, LE = C; Ohkubo et al., 1995; SR = I, LE = C; Klein et al., 1995; SR =
I, LE = C

*Progression to neuropathy:* DCCT Research Group 1993, SR = I, LE = A;
DCCT 1995, SR = I, LE = A

*Progression to amputations:* Klein et al., 1994; SR = I, LE = B;
Mayfield et al., 1996; SR = I, LE = B

*Myocardial infarction, stroke:* DCCT Research Group 1993, SR = IIb, LE
= A; Ohkubo et al., 1995; SR = IIb, LE = A; Anderson et al., 1995; SR =
IIb, LE = B; Singer et al., 1992; SR = IIb, LE = B; Abraira et al.,
1997; SR = IIb, LE = A; Klein et al., 1995; SR = IIb, LE = B

*Effect of DM on life expectancy:* Panzram et al., 1987; SR = I, LE = B;
Marks 1975 SR = I, LE = B; Goodkin 1975 SR = I, LE = B; Singer 1992 SR =
I, LE = B

*Duration of DM and incidence of end-stage microvascular complications:*
Klein et al., 1994, 1995; SR = I, LE = B; Palmberg P et al., 1981; SR =
I, LE = B; UKPDS 1995 SR = I, LE = B; Humphrey et al., 1989; SR = I, LE
= B

*Effect of ethnicity on glycemic target levels:* Haffner et al., 1988;
SR = IIa, LE = B; Hamman et al., 1989; SR = IIa, LE = B; Lee et al.,
1992; SR = IIa, LE = B; Nelson et al., 1988; SR = IIa, LE = B; Rabb et
al., 1990; SR = IIa, LE = B

*Pre-existing retinopathy or microalbuminuria as a risk factor for
progression:* DCCT Research Group 1993, 1995 SR = I, LE = A; Ohkubo et
al., 1995; SR = I, LE = A

*Progression to microvascular complication (primary laser therapy):*
UKPDS 1998; SR = I, LE = A

# Adjust the Glycemic Target According to Patient's Factors 

Objective

To ensure that the recommended target value for HbA~1~c can be safely
achieved by the patient, taking into consideration individual risk,
benefit, and preference.

ANNOTATION

The risks of therapy are different for each patient, depending upon the
individual's medical, social, and psychological status. Thus, the risks
of a proposed therapy must be balanced against the potential benefits.

DISCUSSION

1.  Factors to consider in lowering the HbA~1~c target include but are
    not limited to:

-   Appropriate medical support and psychosocial environment

-   Pregnancy or the intention to become pregnant

-   Willingness and ability to self monitor blood glucose and to make
    appropriate lifestyle change.

2.  Factors to consider in raising the HbA~1~c target include but are
    not limited to:

-   History of severe, recurrent hypoglycemia

-   The possible consequence of adverse effects associated with
    hypoglycemia (e.g., consider cardiovascular disease,
    anticoagulation, use of dangerous equipment, etc.)

-   Alcohol or substance abuse

-   The presence of multiple end-stage microvascular complications,
    including macular edema, proliferative retinopathy and
    macroproteinuria, especially with elevated serum creatinine

-   Symptomatic cardiovascular disease.

3.  Factors that demonstrate patient preference:

-   Quality of life

-   Specific risks of patient therapeutic options.

# Set Target Range After Discussion with Patient

OBJECTIVE

To establish the patient's readiness and willingness to achieve the
target.

ANNOTATION

Target range of glycosylated hemoglobin based upon life expectancy,
microvascular complications, and familial history, is a starting point
for negotiation with the patient. It does not mean that a lower HbA~1~c
level will not be beneficial, nor does it mean that the provider and the
patient should not negotiate a lower one. Rather, it implies that there
is a decreased benefit of excellent glycemic control in the setting of
limited survival expectation or pre-existing moderate-to-advanced
microvascular complications of diabetes. These factors should be taken
into account when evaluating the risks and benefits of pharmacological
therapy as well as patient preferences. In addition, it should be
recognized that reduction in risk from decreasing HbA~1~c is a
continuum, so a negotiated target level does not have to be exactly 7.0,
8.0, or 9.0 percent. The patient should make the final decision as to a
specific target value of glycemic control after a full discussion of the
risks and benefits of therapy with his or her provider.

Providers should consider that some patients may require more immediate,
urgent, or aggressive management in primary care. Some cases may require
referral to an endocrine/diabetes clinic, or to a case manager in order
to meet glycemic control target goals.

# Is Patient High Risk?

OBJECTIVE

To identify high risk patients for whom subspecialty consultation would
be appropriate to assist in the development of a treatment plan and/or
to supervise ongoing care.

ANNOTATION

High risk DM patients include those who:

-   Have type 1 DM (especially patients with history of hospitalizations
    for metabolic complications and/or patients who are receiving
    intensive insulin therapy)

-   Have recurrent episodes of incapacitating hypo- and/or hyperglycemia

-   Have poor recognition of hypoglycemia and who have history of severe
    hypoglycemic reactions (including coma, seizures, or frequent need
    for emergency resuscitation)

-   Have new-onset insulin-requiring DM

-   Have visual and/or renal impairment

-   Have psychosocial problems (including alcohol or substance abuse)
    that complicate management

-   Have HbA~1~c \> 9.5 percent.

The Diabetes Quality Improvement Project (DQIP), a federal/private
sector coalition, reached the consensus that HbA~1~c \> 9.5 percent
represents high-risk glycemic control even in the absence of case mix
adjustment. Consequently, providers should consider a patient with
HbA~1~c \> 9.5 percent for aggressive management on an expedited basis.

Patients who are on high-dose multiple agents should also be consider
for referral.

# Does Patient Require Insulin?

Objective

To identify patients for whom insulin treatment is the only viable
alternative.

Annotation

All patients with type 1 DM by definition must receive insulin therapy.
Additionally, patients with type 2 diabetes or diabetes of undetermined
cause who exhibit significant or rapid weight loss and/or persistent
non-fasting ketonuria have at least severe relative insulin deficiency
and will require insulin therapy on an indefinite basis.

Weight loss and ketonuria are indications of a catabolic state for which
insulin is preferred therapy in type 2 DM. Insulin is an anabolic
hormone, and is often beneficial in such circumstances, especially if
there is a concurrent illness.

# Institute/Adjust Insulin, Consider Referral

Objective

To improve/achieve glycemic goals using insulin.

Annotation

Because type 1 DM is caused by absolute insulin deficiency, insulin
replacement therapy is the only viable treatment option. Insulin therapy
for patients with type 1 DM must be individualized and customized
according to multiple lifestyle factors. Institution and adjustment of
insulin therapy is most efficiently accomplished by referral to a
diabetic clinic with multidisciplinary resources including
diabetologists, diabetic nurse, educator/managers, and registered
dietitians. If expedient referral cannot be accomplished, the primary
care provider should institute \"survival\" insulin therapy. This can be
initiated at a calculated total daily dose (TDD) of 0.5 units/kg body
weight/day. Two-thirds of the TDD administered 30 minutes prior to
breakfast as two parts human NPH insulin and one part human regular
insulin. The remaining thirds of the TDD can be split equally, as human
regular insulin 30 minutes before supper and as human NPH insulin at
bedtime.

Discussion

See Appendix G3, Insulin Therapy.

# Assure Appropriate Intervention to Address Patient Adherence

OBJECTIVE

To assure proper patient monitoring and contact with the health care
team.

ANNOTATION

An important touchstone for successful management of type 2 diabetes is
comprehensive patient education and internalization of self-management
knowledge and performance skills (see Module M). Ongoing professional
contact allows for feedback, answering questions, reinforcing positive
skills and behaviors, and improving suboptimal skills and behaviors.
Ideally, the diabetes nurse educator/manager and dietetic consultant
will be involved as partners with the primary care provider. Together
they should assess the patient\'s knowledge, performance skills, and
barriers to full compliance. If psychosocial, personal, or financial
barriers are identified, additional resources, such as mental health,
medical social work, or financial counselors can be consulted as
applicable.

# Initiate/Adjust Therapy 

OBJECTIVE

To achieve glycemic target goals by the most cost effective and least
invasive means.

ANNOTATION

Long-term outcomes (survival and occurrence of microvascular
complications) of treatment of DM are related to the degree of glycemic
control achieved, but not to the means used to achieve control
(diet/exercise vs. oral hypoglycemic agent vs. insulin, or any known
combination therapy). Based on this principle, therapy should be
tailored to individual preferences, needs, and pragmatic considerations,
such as cost and ease of compliance.

Each newly diagnosed patient with DM should attempt non-pharmacological
treatment with diet and lifestyle modification prior to use of
medications. There is considerable evidence from the UKPDS that type 2
DM is a progressive disease, which will necessitate the adjustment of
medication dosage and additive pharmacological therapy over time. Table
G2 summarizes a concept of sequential treatment commonly employed in
clinical practice.

###### Table G2. Recommended Option for Type 2 DM

+-------------------------+-------------------------+------------------+
| > **Therapy**           | > **Drugs**             | > **Expected     |
|                         |                         | > reduction in   |
|                         |                         | > HbA1c**        |
|                         |                         | >                |
|                         |                         | > Over a 2 to 3  |
|                         |                         | > month period   |
|                         |                         | > of follow-up   |
+-------------------------+-------------------------+------------------+
| > Lifestyle             | > None                  |                  |
| > modification, diet    |                         |                  |
| > and exercise          |                         |                  |
+-------------------------+-------------------------+------------------+
| > Lifestyle             | > Sulfonylurea or       | > 1-2 percent    |
| > modification, diet    | > biguanide             |                  |
| > and exercise          |                         |                  |
| >                       |                         |                  |
| > **Monotherapy** with  |                         |                  |
| > oral agent            |                         |                  |
+-------------------------+-------------------------+------------------+
| > Lifestyle             | > Sulfonylurea +        | > 1-2 percent    |
| > modification diet and | > biguanide             | >                |
| > exercise              | >                       | > 0.5 to 1       |
| >                       | > Sulfonylurea or       | > percent        |
| > **Combination** (add  | > biguanide +           | >                |
| > a second oral agent)  | > alpha-glucosidase     | > 0.7 to 1.75    |
|                         | > inhibitor             | > percent        |
|                         | >                       | >                |
|                         | > Sulfonylurea or       | > 0.1 to .3      |
|                         | > biguanide +           | > percent        |
|                         | > thiazolidenedione     |                  |
|                         | >                       |                  |
|                         | > Biguanide +           |                  |
|                         | > repaglinide           |                  |
+-------------------------+-------------------------+------------------+
| > Insulin with oral     | > Biguanide + insulin   |                  |
| > agent                 | >                       |                  |
|                         | > thiazolidenedione +   |                  |
|                         | > insulin               |                  |
|                         | >                       |                  |
|                         | > Sulfonylurea +        |                  |
|                         | > insulin               |                  |
+-------------------------+-------------------------+------------------+
| > Insulin               | > Insulin alone         |                  |
+-------------------------+-------------------------+------------------+
| > Referral              |                         |                  |
+-------------------------+-------------------------+------------------+

1.  Individual treatment goals must be established with the patient
    based on the extent of the disease, comorbid conditions, and patient
    preferences.

2.  Institution of diet and exercise is usually the appropriate initial
    management in patients with new onset type 2 diabetes, depending
    upon severity of symptoms, pyschosocial evaluation, and overall
    health status. Encourage diet and exercise and lifestyle
    modification.

3.  If treatment goals are not achieved with diet and exercise alone, a
    sulfonylurea or biguanide (i.e., metformin) should be used as first
    line drug therapy. For patients with significant obesity, initial
    monotherapy with a biguanide may be preferable.

4.  If the glycemic target level is not achieved with either agent
    alone, a biguanide (i.e., metformin) may be combined with a
    sulfonlyurea.

5.  Alpha-glucosidase inhibitors may be used in conjunction with a
    sulfonylurea or sulfonylurea/biguanide combination in patients whose
    postprandial blood glucose is inadequately controlled but whose
    fasting glucose is in the desired range on sulfonylurea or
    sulfonylurea/biguanide regimens.

6.  Addition of bedtime insulin therapy to an existing combination oral
    agent regimen may be a treatment option when the glycemic control
    target is not achieved by an all-oral regimen.

7.  In patients treated with large doses of insulin, addition of a
    thiazolidenedione may reduce the insulin requirement and produce
    improved glycemia, with reduction of HbA~1~c by 1 to 2 percent.
    Thiazolidenediones are not recommended as first-line monotherapy.

8.  Intermediate-acting insulin in a single evening dose may be used in
    conjunction with oral monotherapy with either sulfonylurea or
    biguanide, or in addition to combine sulfonylurea/biguanide therapy.
    It may also be used as a single agent, when given in multiple daily
    doses, if the glycemic control target has not been reached with oral
    therapy. The use of insulin Lispro is not recommended for routine
    use in treatment of type 2 DM, as there is no evidence that it has
    any inherent superiority to less costly insulin preparations.

9.  Carefully selected individuals may benefit from three-drug oral
    hypoglycemic therapy. In general, such patients may benefit from
    referral to a diabetes care team.

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10. Patients who fail to attain target glycemic control goal despite
    ongoing care, education, and medication adjustment in the primary
    care setting may benefit from referral to a diabetes care team for
    comprehensive assessment and intensified management.

There is no evidence that blood glucose monitoring in stable type 2 DM
patients is of clinical benefit. If self-monitoring is to be done, a
twice-weekly regimen is usually sufficient. Special situations, such as
acute intercurrent illness, frequent hypo- or hyperglycemia, or changes
in medication regimen, may justify more frequent monitoring on a
temporary basis.

Discussion

See Appendix G4, Pharmacological Therapy.

# Determine If There Are Side Effects or Contraindications to Current Treatment 

OBJECTIVE

To modify therapy due to side effects of drug therapy.

ANNOTATION

Side effects of pharmacological therapy can include drug-drug,
hypoglycemia, and specific adverse drug effects. Patients may experience
side effects from medications if adjustments are not made when patients
undergo medical or surgical procedures, have a change in their
condition, or develop an intercurrent illness.

Patients with recurrent or severe hypoglycemia should be evaluated for
precipitating factors that may be easily correctable (e.g., missed
meals, incorrect administration of insulin---dosage or timing---,
exercise, etc.). In many cases, a simple adjustment can be made in
nutrition, exercise, medication and/or patient self-monitoring. In
patients with near-normal glycemic control (notably patients with type 1
DM on intensive insulin treatment or patients with autonomic
neuropathy), it may be necessary to relax the degree of glycemic
control, at least temporarily. Complex adjustments may best be
accomplished through co-management with a diabetes team.

Certain drug effects, e.g., gastrointestinal symptoms, may improve over
time or with modification of the dosage regimen and thus may not
necessitate discontinuance of medication. On the other hand, some drugs
may have adverse effects that require vigilant monitoring, such as
frequent measurement of serum liver function tests in patients treated
with troglitazone. Finally, patients may develop contraindications to
continued use of a []{.mark}previously successful maintenance
medication. Examples would include newly recognized renal insufficiency
or severe congestive heart failure in a patient treated with metformin.

DISCUSSION

See Appendix G4, Pharmacological Therapy.

# Are There Problems with Patient Adherence?

OBJECTIVE

To identify barriers to full adherence to the prescribed treatment
regimen.

ANNOTATION

It is appropriate to briefly review adherence to the prescribed
nutritional and exercise regimens as well as to review the dosages and
timing of administration of medication. If the patient does not achieve
his or her target range, the practitioner should look for barriers to
patient adherence to regimen. Barriers may include miscommunication,
lack of education, lack of understanding, financial or social barriers,
psychological barriers and cultural beliefs (e.g., learned
helplessness). In addition, the patient may have treatment preferences
that are not being addressed.

The patient may be considered for case management or referral to a
behavioral or a financial counselor, as appropriate.

DISCUSSION

See Module M, Patient Self-management and Needs Assessment.

# Should Glycemic Control Target Be Adjusted?

OBJECTIVE

To determine whether the recommended glycemic control goal remains
appropriate for the patient.

ANNOTATION

Treatment goals should be periodically reassessed based upon patient
specific factors, including changes in patients health status, adverse
drug reactions, adherence to therapy, and preferences.

Relative indications for raising the target glycemic goal include
inability or unwillingness to adhere to a more intensive regimen, or an
unacceptable risk of hypoglycemia relative to anticipated benefits of
near-normal glycemia.

If the target range remains appropriate but has not been reached, the
provider and patient should identify the reasons why the target has not
been achieved and take appropriate action.

Reasons to consider lowering the target glycemic control goal include
removal of barriers to improved control (e.g., substance abuse,
intercurrent illnesses, adherence issues) and resolution of relative
contraindications. See also annotation D above.

# Follow-Up

Objective

To maintain glycemic control and ensure proper patient monitoring by the
health care team.

Annotation

The patient should be scheduled for appropriate follow-up to evaluate
response, tolerability to therapy, goal re-assessment and management of
acute and chronic problems. The frequency of primary care provider
visits for the diabetic patient who is meeting treatment goals and who
has no unstable chronic complications should be individualized. When
there is a sudden change in health status or when changes are made to
the treatment regimen, follow-up within one month or sooner may be
appropriate.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# Appendix G1. Measurements of Glycemic Control

> There are three types of tests of glycemic control currently in use:

1.  For long-term glycemic control (past 3 to 4 months), HbA~1~c is
    preferred.

2.  For short-term glycemic control (past 10 to 20 days) fructosamine
    can be used, but is not widely available.

3.  Single point measurement of blood sugar can be measured on venous,
    plasma, or capillary samples in the lab with a glucose meter.

## GLYCOSYLATED HEMOGLOBIN---HbA~1~c

The terms \"glycated\" and \"glycosylated\" hemoglobin are used
interchangeably in the literature. The terms are used to describe the
reaction product between sugar and a protein.

There are four HbA~1~ components: HbA~1~a~1~, HbA~1~a~2~, HbA~1~b,
HbA~1~c. HbA~1~c is the marker of choice for the assessment of risk for
the development of microvascular complications.

Because HbA~1~c can be measured by a variety of different methodologies,
the normal range varies by methodology. The lab reports the percentage
of hemoglobin that is glycosylated. A HbA~1~c for an individual patient
should be interpreted as the percent above high normal range for the
facility laboratory, rather than as an absolute value. It is recommended
that facilities use a method that participates in the National
Glycohemoglobin Standardization Program (NGSP).

If a patient has a hemoglobinopathy (e.g., Hb S, C, D, G, F and
intermediary product) consult with the Laboratory Chief to determine
whether or not the glycosylated hemoglobin test methodology is affected
by the presence of hemoglobinopathy. Normal range varies by methodology.

Facilities that measure total GHb should be able to provide accurate
HbA~1~c equivalency values. However, there is no analytic system that
measures HbA~1~c and is able to report HbA~1~c equivalency measures

Certain HbA~1~c measurements may also be unreliable in the presence of
the following conditions: hemolytic anemia, uremia, or pregnancy. Serum
fructosamine measurement may be considered as an alternative test in
these circumstances.

## GLUCOSE MEASUREMENTS

Single point measurement of blood sugar can be determined from venous
samples and capillary glucose measurements. Only venous samples should
be used for the diagnosis of DM. Capillary blood sugar measures can be
used for home monitoring.

The most common user error associated with self-managed blood glucose
(SMBG) is inadequate sample size. Depending upon the meter used, this
error can lead to a significant discrepancy between the actual and
recorded blood glucose. A user\'s technique and maintenance procedures
should be reviewed annually or as indicated.

Assuming that the mean SMBG or point of care or laboratory glucose
measurements are accurate, multiple readings at various time points can
be averaged to obtain approximate HbA~1~c levels by using the equation
below from the DCCT database.

**Table G3. Estimate of HbA~1~c**

  ------------------------------------ ----------------------------------
  **Mean Blood Glucose**               **Estimated HbA~1~c**

  120 mg/dL Glucose =                  6 % HbA~1~c

  150 mg/dL Glucose =                  7 % HbA~1~c

  180 mg/dL Glucose =                  8 % HbA~1~c

  Every 30 mg/dL increase =            1 % increase
  ------------------------------------ ----------------------------------

**MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING**

# Appendix G2. Estimating Benefit and Risk of Glycemic Control

Determination of an optimal target HbA~1~c level is based upon the risk
for developing microvascular complications. The individual risk is
dependent on life expectancy, absence or presence of pre-existing
microvascular complications, and genetic factors.

## Determine life expectancy

Statistics for the life expectancy of a population can be derived from
the observed mortality rates of that population. An example commonly
used in medicine would be the life expectancy of patients with a
particular type of end stage of cancer. The population would have an
average survival, with a wider range of survival into which almost all
patients would fall. While it would be impossible to tell a patient
exactly how long he or she would live; it would be possible to estimate
his/her life expectancy. Based upon life expectancy and mortality rates
due to the disease, the provider and patient should discuss treatment
options.

Longitudinal studies of the life expectancy of patients with DM
corroborate that patients with DM have a shortened life span relative to
patients without DM (Eastman, 1997; Diabetes Care 1997). However, the
format of the data from such studies is not easily transposed. These
data have been generated based upon a computer model that incorporates
data from the Framingham Study. Except for end stage renal disease, the
model assumes that microvascular complications do not affect survival,
although they do predict progression to blindness, amputation, and
dialysis.

![](media/image7.png){width="5.999305555555556in"
height="4.339583333333334in"}

For any given age at the time of diagnosis of DM, the years of life
remaining after diagnosis are provided in the 25th, 50th, 75th, and 95th
percentiles. It can be assumed that populations of patients with DM and
other health conditions would have a survival rate less than the mean
life expectancy (use 25th percentile), and that patients without
co-morbid conditions and with a favorable family history would have a
survival rate greater than the mean life expectancy (use 75th or 95th
percentile).

![](media/image8.png){width="5.999305555555556in"
height="4.259722222222222in"}

Co-existing conditions (e.g., CHF, AIDS, COPD, cirrhosis, cancer, etc.)
have a significant effect on survival. Aggressive treatment of
cardiovascular risk factors, including smoking cessation, may increase
life expectancy. In addition, adherence to general preventive practices
(for example immunizations, screening for colon, prostate, and breast
cancers) is also predicted to increase life expectancy in the American
population. Thus, for a patient with DM, an estimate of life expectancy
for a given percentile can be obtained by determining the patient\'s age
at the time of diagnosis of DM and determining the average (mean) years
of life remaining by subtracting the time (in years) that has elapsed
from the time of diagnosis. Providers must then use their best judgment
to raise or lower it based upon coexisting medical conditions and family
history. It is recommended that unless a patient has a known condition
that will decrease his life expectancy that a value above the mean be
used.

While a patient\'s age is clearly the predominant factor in estimating
life expectancy, this approach ensures that the life expectancy estimate
used in determining target glycemic ranges for a patient is also based
upon the patient\'s health state and the judgment of the clinician.

## Determine presence of microvascular complications

The presence of microvascular complications (e.g., retinopathy and
microalbuminuria; see Modules E, Eye Care, and R, Renal Disease,
respectively) increases the probability that end stage microvascular
complications will occur as compared to the probability that these
complications will occur in a patient without microvascular
complications but with a similar life expectancy.

## Consider family history

The risk stratification approach can be extended by the practitioner to
include family history of microvascular complications. A familial
history of diabetic nephropathy or retinopathy predisposes a first
generation relative to the development of microvascular complications.
In patients with a given strong family history, defined as diabetic
end-stage renal disease, or visual loss secondary to diabetic
retinopathy in a first degree relative, consider leaning towards a lower
HbA~1~c target value.

## RELATIVE AND ABSOLUTE RISK REDUCTION

[]{.mark}

Until 1993, there were no RCTs to support the theory that tight glycemic
control prevented complications of diabetes. Until more recently the
research trail leading to confirmation of benefits of glycemic control
to the progression of microvascular disease has included studies limited
in scope to a target organ, or a particular patient grouping and
involved relatively short time frames. However, these studies pointed
towards further definition of the benefits of glycemic control and the
potential value of more comprehensive studies such as now realized.
Analysis of the risk reduction in microvascular complications from the
diabetic control and complication trial (DCCT) concludes that the
relative risk reduction of intermediate microvascular complications of
DM (e.g., development of background retinopathy and microalbuminuria)
can be reduced by about 40 percent for each one percent decrease in
HbA~1~c in patients with type 1 DM.

However, it should be noted that the conclusions of the DCCT study were
based on intermediate microvascular complications. Progression to
proliferative retinopathy was uncommon, and no patients progressed to
renal insufficiency. Therefore, it should be recognized that maximal
benefits of glycemic control in preventing the progression of
microvascular disease to the endpoints of visual loss or chronic renal
insufficiency accrue over a period of time longer than that of the study
period of the aforementioned trial.

More recently the issue of incidence and progression of complications in
type 2 diabetic patients over a 10 year period of observation was
addressed by the UKPDS. This study compared 3,867 type 2 diabetics
randomized into two groups, 1) intention to treat by diet alone and 2)
intention to treat by intensive pharmacological intervention. These
studies demonstrated a 35 percent decrease in microvascular
complications for every 1 percent decrease in HgbA~1~c and the decrease
was continuous to a HgbA~1~c of \> 6 percent. While the UKPDS intensive
treatment group only achieved an 11 percent decrease in HgbA~1~c
compared with the control group (controls 7.9, intensive 7.0) when
compared to the 20 percent HgbA~1~c decrease achieved by the intensive
group in the DCCT, the 25 percent decrease in overall microvascular
complications in the UKPDS was similar to the decrease in microvascular
complications achieved in the DCCT. Thus the UKPDS study supports type 2
diabetes glycemic control in a manner similar to the DCCT in type 1
diabetes and together these studies establish that blood glucose control
substantially reduces the incidence of microvascular complications in
diabetes. Improved glycemic control is appropriate for all patients.
However each patient must be assessed individually taking into account
whether the patient is of advanced physiologic age, suffers from
co-morbid conditions affecting his or her life expectancy, demonstrates
the progression of microvascular disease or some combination of these
conditions. Computer models based upon patient data from type 1 and type
2 diabetics can provide estimates of the incidence of microvascular
complications, the expected decrease in microvascular complications
resulting from improved glycemic control and life expectancy estimates
(Eastman et al., 1997; Vijan et al., 1997). These models provide
population risks of risk, and were used in providing an estimate of risk
over time as well as an estimate of benefit from improved glycemic
control. The resulting estimates of absolute risk reduction, defined as
decreases in visual loss and end stage renal disease that occur with a
given decrease in percent HbA~1~c reduction, indicate that in some
instances the progression of co-morbid conditions factored with advanced
physiological age preempt the progression of pathological processes
associated with glycemic control. These are instances when aggressive
efforts to achieve ideal glycemic control are neither cost effective nor
likely to result in improved outcomes. See Table G1 and Annotation C for
suggested upper limits of HbA~1~c levels in categories of patients
referred to above.

Taken alone or together, both computer modeling and clinical studies
thus far indicate that the absolute risk reduction in end-stage
microvascular disease over a patient\'s lifetime is the major
determinant of the target range of glycemic control for a patient, and
will influence the risk/benefit analysis of therapeutic options.
Improvement in macrovascular diseases outcomes associated with glycemic
control has not yet been proven in RCTs. Observational studies
demonstrate an association between increased HbA~1~c and cardiovascular
disease and cardiovascular mortality risk that achieves statistical
significance only for women. There are no intervention trials that
conclusively demonstrate that improved glycemic control will alter
cardiovascular morbidity and/or mortality. The DCCT and the Ohkubo
trials show a nonsignificant trend towards reduced cardiovascular events
with intensive insulin therapy, while the VA Cooperative trial
demonstrated a nonsignificant increase in cardiovascular events and an
association between decreased HbA~1~c and new cardiovascular events. The
UKPDS demonstrated a 16 percent reduction in the incidence of combined
fatal and non-fatal myocardial infarction among intensively treated
patient group, but the risk reduction was not statistically significant
(*p* = 0.052) at the 10 year data collection point. This study will
produce more data at 15 years and the end points (fatal and non fatal
myocardial infarctions) will be again determined at that time.

#  

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# Appendix G3. Insulin Therapy

**GENERAL CONSIDERATIONS**

Types, frequency, and dosages of insulin must be individualized. Factors
to be considered include:

-   Type 1 or type 2 DM

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-   Age

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-   Weight (presence or absence of obesity)

-   Co-morbid conditions

-   Presence of autonomic neuropathy

-   Concomitant medications (specifically beta-blockers)

-   Patient ability to perform self-glucose monitoring and inject
    insulin accurately

-   Risks and benefits of hypoglycemia, including psychosocial factors

-   Magnitude and pattern of hyperglycemia.

## INSULIN THERAPY IN TYPE 1 DM

Insulin dosages vary widely among patients, even when other factors are
similar. For patients with new onset of type 1 DM, it is recommended
that initial therapy be individualized in consultation with a Diabetes
Team.

Patients with type 1 DM generally are more sensitive to changes in
insulin dosage and far more susceptible to episodes of hypoglycemia than
individuals with type 2 DM. According to a resource intensive controlled
randomized trial (DCCT), for patients with type 1 DM treated on
intensive insulin regimens the risk of severe hypoglycemic reactions was
increased by 300 percent. Patients on intensive insulin therapy should
be managed in collaboration with a DM Team.

## 

## INSULIN THERAPY TYPE 2 DM

Many patients with type 2 DM can achieve target glycemic levels with a
single bedtime injection of insulin, or split mixed insulin. Some
individuals will require intensified regimens to achieve their target
glycemic range. Intensified regimens may include a short acting insulin
before meals plus Ultralente before breakfast and/or bedtime OR a mix of
intermediate plus short acting insulin before breakfast and short acting
insulin before dinner and an intermediate-acting bedtime insulin. The
safe way to begin insulin is to start with a conservative starting dose
and increase it gradually until the desired level of control is
achieved. For patients with ≤ 125 percent ideal body weight; or BMI \<
27, a total dose of 15 units, 10 units before breakfast and 5 units
before supper, could be recommended; in patients with ≥ 125 percent
ideal body weight, the initial dose could be doubled. The individually
assessed risk for hypoglycemia may temper the starting dose
recommendation.

The following tables are from the VA Medical Advisory Panel (MAP)
Pharmacological Management of Non-Insulin Dependent Diabetes Mellitus
(NIDDM), 1998.

**Table G3a. General Guidelines for Insulin Adjustment in the Type 2 DM
Patient on Split Regimens**

+-----------------------------------------------------------------------+
| -   If the morning fasting blood sugar is off target, adjust the      |
|     evening NPH or switch evening NPH to bedtime                      |
|                                                                       |
| -   If the evening serum glucose is off target, adjust the morning    |
|     NPH                                                               |
|                                                                       |
| -   If the evening glucose continues to be off target, have the       |
|     patient check the pre-lunch glucose                               |
|                                                                       |
| -   If the pre-lunch glucose is off target, adjust the morning        |
|     Regular insulin                                                   |
|                                                                       |
| -   If the bedtime glucose is off target, adjust the evening Regular  |
|     insulin                                                           |
+-----------------------------------------------------------------------+

# Table G3b. Comparison of Insulin Preparations (a) (b)

+-------------+---------+----------+-----------+----------+----------+
| **Insulin** | **Onset | **Peak   | *         | **Co     | **Appe   |
|             | (hrs)** | (hrs)**  | *Duration | mpatible | arance** |
|             |         |          | (hrs)**   | Mixed    |          |
|             |         |          | (c)       | with:**  |          |
+-------------+---------+----------+-----------+----------+----------+
| ### **RAP   |         |          |           |          |          |
| ID-ACTING** |         |          |           |          |          |
+-------------+---------+----------+-----------+----------+----------+
| > Regular   | > 0.5-1 | > 1-5    | > 6-10    | > all    | > Clear  |
+-------------+---------+----------+-----------+----------+----------+
| > Lispro    | > 0     | >        | > 3-6.5   | > Ultral | > Clear  |
|             | .25-0.5 |  0.5-2.5 |           | ente-NPH |          |
|             |         |          |           | > (d)    |          |
+-------------+---------+----------+-----------+----------+----------+
| ***         |         |          |           |          |          |
| INTERMEDIAT |         |          |           |          |          |
| E-ACTING*** |         |          |           |          |          |
+-------------+---------+----------+-----------+----------+----------+
| > NPH       | > 1-2   | > 6-14   | > 16-24+  | >        | > Cloudy |
|             |         |          |           |  regular |          |
+-------------+---------+----------+-----------+----------+----------+
| > Lente     | > 1-3   | > 6-14   | > 16-24+  | >        | > Cloudy |
|             |         |          |           |  regular |          |
+-------------+---------+----------+-----------+----------+----------+
| ### **LO    |         |          |           |          |          |
| NG-ACTING** |         |          |           |          |          |
+-------------+---------+----------+-----------+----------+----------+
| >           | > 4-6   | > 8-20   | > 24-28   | >        | > Cloudy |
|  Ultralente |         |          |           |  regular |          |
+-------------+---------+----------+-----------+----------+----------+

(a) Adapted from AHFS Drug Information, American Society of
    Health-System Pharmacists, Inc., 1998

(b) Onset, peak, and duration are parameters for non-human insulin
    preparations; in general, human preparations have shorter times of
    duration

(c) Duration may depend on type of preparation and route of
    administration as well as patient related variables. In general, the
    larger the dose of insulin, the longer the duration of activity

(d) The effects of mixing insulin Lispro with insulins of animal source
    or insulins produced by manufacturers other than Eli Lilly have not
    been studied.

# Table G3c. Insulin Regimen Examples

+------------------------+---------------------------------------------+
| **Bedtime Dosing of    | -   Begin with 10 to 15 units at bedtime (a |
| NPH or Lente Insulin   |     dose equal to the morning glucose/18    |
| in Addition to an Oral |     \[a\]) A dose equal to the morning      |
| Agent**                |     glucose/18 (a)                          |
|                        |                                             |
|                        | -   Verify that the pre-dinner glucose      |
|                        |     remains in control                      |
+------------------------+---------------------------------------------+
| **Split Mixed Regimen  | -   Inject 2/3 of the total insulin         |
| with NPH/Regular** (c) |     requirement in the morning, with a      |
|                        |     NPH/Regular ratio of 70:30              |
|                        |                                             |
|                        | -   Inject 1/3 of the total insulin         |
|                        |     requirement in the evening, with a      |
|                        |     NPH/Regular ratio of 50:50 (b)          |
+------------------------+---------------------------------------------+
| **Once-daily Morning   | -   Good for elderly or non-compliant       |
| NPH insulin**          |     patients                                |
|                        |                                             |
|                        | -   Inject 30 to 60 minutes before          |
|                        |     breakfast                               |
|                        |                                             |
|                        | -   Usual dosage \< 40 units/day            |
+------------------------+---------------------------------------------+

(a) Adapted from: Edelman SV, White D, Henry RR. Intensive insulin
    therapy for patients with type 2 diabetes. **Current Opinion in
    Endocrinology and Diabetes** 1995;2:333-340

(b) These are a few examples, optimal regimen depends on the individual
    patient

(c) Always counsel patients to mix regular insulin in syringe first,
    followed by NPH; mixtures of regular and lente insulins should be
    injected immediately. Inject regular insulin 30 to 60 minutes before
    a meal; Lispro insulin should be injected within 15 minutes before a
    meal; mixtures of Lispro and Humulin N or Humulin U should be
    administered immediately. Manufacturer specific storage guidelines
    should be followed.

**MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING**

# Appendix G4. Pharmacological Therapy

#### GENERAL APPROACH

It is important to educate the patient and family about type 2 DM and
its treatment. Together, formulate a plan for achieving glycemic control
by encouraging an active, healthy lifestyle that includes exercise and
diet and medications when necessary. Obtain agreement of goals in
treatment, and provide supportive follow-up.

Provide education on glucose monitoring, prevention and treatment of
complications, hypoglycemia awareness and treatment, and pharmacological
therapy, as appropriate.

## NON-PHARMACOLOGIC THERAPY

Lifestyle changes include diet (see Module M, Self-management and
Education), exercise for at least 30 minutes per day on most days of the
week (as appropriate, after a detailed medical examination), weight loss
if indicated, and smoking cessation. Limit alcohol to no more than 2
drinks per day for men and 1 drink per day for women (1 drink = 12
ounces of beer, 5 ounces of wine, or 1.5 ounces of distilled spirits).
Diet and exercise should be given at least a 3 month trial before drug
therapy is started unless fasting glucose [\>]{.underline} 250 mg/dL or
[\<]{.underline} 250 mg/dL with symptoms of hyperglycemia.

## PHARMACOTHERAPY

#### General Considerations

When selecting an agent, consideration must be given to efficacy,
contraindications, drug interaction, side effects, cost, and patient
preferences.

Elderly patients are at a higher risk for drug-associated hypoglycemia,
due to altered metabolism and excretion rates, impaired symptom
recognition, and potentially attenuated counter-regulatory responses.
Patients and their families should be instructed to recognize signs and
symptoms of hypoglycemia and its management.

## Sulfonylureas

a.  Sulfonylureas lower blood glucose by stimulating insulin release
    from beta cells in the pancreas.

b.  A second-generation sulfonylurea is the first-line agent, based on
    safety. HbA~1~c should be measured 3 to 6 months after initiation
    and changes in therapy. A first-generation sulfonylurea can be used
    as an alternate agent in selected patients. However, chlorpropamide
    should only be used in patients \< 65 years old who are already
    stable on the medication; it should not be used as a new agent.

c.  No difference in long term efficacy or failure rate has been
    demonstrated among the sulfonylureas. The average absolute decrement
    in HbA~1~c when these agents are used as monotherapy is one to two
    percent.

d.  If the response to a single daily dose does not achieve treatment
    goals, dividing the dose may be effective. The dose response to
    these agents flattens out before maximum dosages are reached.

e.  Pharmacological differences in sulfonylureas may have important
    clinical implications, particularly with regard to risk of
    hypoglycemia (see Tables G4c, Drug Interactions with Oral
    Hypoglycemic Agents). The preferred agents have shorter half-lives,
    and inactive metabolites.

f.  Certain medications may interact with or potentiate the action of
    sulfonylureas (see Table G4c, Drug Interactions with Oral
    Hypoglycemic Agents).

g.  Approximately 15 percent of patients may never achieve adequate
    glucose control (primary failure) and 5 to 10 percent per annum lose
    control of blood glucose (secondary failure).

h.  If the patient does not have an initial response to therapeutic
    doses of a sulfonylurea (primary failure), evaluate patient for
    possibility of type 1 DM. Make sure patient has no intercurrent
    illnesses or drugs that can interfere with glucose control and
    assess adherence to diet and drug therapy. For patients experiencing
    secondary failure, combination therapy with metformin (Hermann 1994;
    DeFronzo 1995; A Klein 1991; Haupt 1991; Trischitta 1992), acarbose
    (Chiasson 1994), or insulin (Chow 1995; Johnson 1996; Soneru 1993;
    Yki-Jarvinen 1992; Wolffenbuttel 1996) is warranted.

[EVIDENCE]{.smallcaps}

Hermann et al., 1994. LE = B; DeFronzo et al., 1995. LE = A; Klein 1991.
LE = B; Haupt 1991. LE = C; Trischitta et al., 1992. LE = B; Chiasson et
al., 1994. LE = B; Chow et al., 1995. LE = B; Johnson et al., 1996. LE =
A; Soneru 1993. LE = C; Yki-Jarvinen et al., 1992. LE = B; Wolffenbuttel
et al., 1996. LE = B

## Biguanides (Currently available: Metformin)

a.  Metformin is a biguanide oral antihyperglycemic agent. The major
    blood glucose lowering effect is through decreasing hepatic glucose
    production with some decrease in peripheral insulin resistance.

b.  Metformin may be considered for use as monotherapy in lieu of
    sulfonylurea in selected patients. (Johansen 1999; Hoffmann 1997;
    UKPDS 34 1998). It may be used in combination with an oral
    sulfonylurea (Hermann 1994; Haupt 1991; Trischitta 1992; De Fronzo
    1995; Klein 1991) acarbose (Rosenstock 1998; Chiasson 1994), or
    insulin (Giugliano 1993; Robinson 1998; Yki-Jarvinen 1999) in the
    event that monotherapy fails to achieve HbA~1~c goal. The effect of
    metformin on glycemic control is additive, due to its different
    mechanism of action.

c.  Efficacy in lowering HbA~1~c is comparable to sulfonylureas; the
    average absolute decrement in HbA~1~c is 1 to 2 percent when
    metformin is used as monotherapy.

d.  A secondary analysis of results from the UK Prospective Diabetes
    Study suggested that metformin in overweight patients was associated
    with only slightly less weight gain over 20 years (2.5 kg or 5.5
    lbs) than sulfonylureas or insulin therapy. Metformin also reduced
    hypoglycemic episodes in the aggregate but the impact on major
    hypoglycemic episodes, defined as an event that required an
    intervention by a health care provider, was nominal. For example, by
    intention-to-treat analysis, the incidence of major hypoglycemic
    episodes for metformin was 0.6 percent and for sulfonylurea was 1.0
    percent (statistical comparison not provided). In almost all
    clinical and laboratory endpoints there was no significant
    difference between metformin and other pharmacological therapies.
    For example, each group had similar diabetes-related mortality,
    macrovascular disease incidence and similar surrogate endpoints such
    as HbA~1~c levels and progression to retinopathy. There was some
    differences noted, for instance in the time to first occurrence of
    any diabetes-related clinical endpoint and in some relative risk
    ratios, but the analysis did not provide specific details on which
    to base a comprehensive comparison across patient groups (UKPDS 34
    1998).

e.  The evidence that metformin should be preferred therapy for all
    overweight diabetics remains controversial and it is unclear whether
    potential benefits outweigh the additional cost. Sulfonylureas
    should be considered as first-line therapy for most patients with
    type 2 diabetes.

f.  Starting doses of metformin range from 500 to 850 mg q am. Elderly
    patients ([\>]{.underline} 65 years old) generally should not be
    titrated to the maximum dose as renal function decreases with age
    thereby increasing the risk of lactic acidosis with metformin.

g.  Use of metformin result in less weight gain, and a reduction in
    plasma triglycerides may also occur. The patient should be advised
    of the transient, dose-related gastrointestinal side effects (e.g.,
    diarrhea, nausea, vomiting, bloating, flatulence, and anorexia).

h.  See Appendix G4b, Drug Interactions with Oral Hypoglycemic Agents,
    for drug interactions.

i.  Patients at risk for lactic acidosis should not receive metformin.
    Specific contraindications include acute or chronic metabolic
    acidosis, renal dysfunction (SCr \>1.5mg/dL \[males\] and SCr \>1.4
    mg/dL \[females\]), and patients with congestive heart failure
    requiring pharmacological management. Metformin use should be
    avoided in patients with hepatic disease or excessive ethanol intake
    or in any patient with a condition associated with hypoxemia,
    dehydration, or sepsis. Metformin use should be temporarily
    discontinued at the time of or prior to intravascular radiocontrast
    studies or surgical procedures. Monitoring renal function to prevent
    lactic acidosis, especially in the elderly is important. (see
    Appendix G4e, Metformin Drug Therapy Precautions

j.  The manufacturer of metformin recommends the addition of a second
    agent for patients not responding to monotherapy with metformin
    after a 4-week trial using maximal dosages. When metformin is being
    used as combination therapy, patients not responding to maximal
    doses of each agent after a 1 to 3 month trial should be switched to
    a different regimen.

EVIDENCE

Hoffmann 1997. LE = B; UKPDS 34 1998. LE = A; Hermann et al., 1994. LE =
B; Haupt 1991. LE = C; Trischitta et al., 1992. LE = B; De Fronzo et
al., 1995. LE = A; Klein 1991. LE = B; Rosenstock et al., 1998. LE = B;
Chiasson et al., 1994. LE = B; Giugliano et al., 1993. LE = B; Robinson
et al., 1998. LE = B; Yki-Jarvinen et al., 1999. LE = B

## Insulin therapy

a.  Insulin is the principal hormone for proper glucose metabolism.
    Human insulin is manufactured by recombinant DNA technology or
    chemical modification of pork insulin (see Table G3a, Comparison of
    Insulin Preparations).

b.  Use as a second-line agent for failure of oral agents. When used in
    combination with a sulfonylurea, 10 to 15 units of NPH or lente can
    be given at bedtime (Johnson 1996; Chow 1995; Wolffenbuttel 1996;
    Soneru 1993; Yki-Jarvinen 1992; Yki-Jarvinen 1999). For obese
    patients (\> 150 percent of ideal body weight) 70/30 insulin may be
    given before dinner. The dose of insulin may be increased by 5 to 10
    units every 1 to 2 weeks until desired fasting glucose is reached.
    For therapeutic options with insulin, see Table G4f, Metformin Drug
    Therapy. Insulin may also be combined with metformin
    (Giugliano 1993. Robinson 1998, Yki-Jarvinen 1999.), acarbose
    (Kelley 1998. Chiasson 1994.), or troglitazone (Schwartz 1998. Buse
    1998).

c.  Efficacy may not increase beyond a single injection per day, though
    multiple daily dose remains a therapeutic option for some patients
    (Abraira 1998; Chow 1995; Wolffenbuttel 1996; Soneru 1993;
    Yki-Jarvinen 1992, 1999). Maximum efficacy is up to a 2 percent
    absolute reduction in HbA~1~c.

d.  Adverse effects may include hypersensitivity reactions, weight gain,
    and hypoglycemia.

e.  Insulin types and species have different pharmacological properties,
    and should not be changed inadvertently. (see Table G3a, Comparison
    of Insulin Preparations). Patients require education on proper
    insulin administration, mixing if necessary, storage, and syringe
    disposal. Certain agents may increase or decrease the hypoglycemic
    effect of insulin. Dosage adjustment may be necessary in renal or
    hepatic impairment, during illness, increased work or exercise, or
    with a change in eating patterns.

f.  Lispro insulin lowers postprandial glucose to a greater extent and
    may have a lower rate of nighttime hypoglycemia when compared to
    regular insulin. HbA~1~c, lipid profile and weight however, were the
    same for both agents (Anderson 1997). Until there is evidence for
    improved long-term outcomes, Lispro is not recommended for most type
    2 patients requiring insulin and should be reserved for use in
    select cases (e.g. frequent nighttime hypoglycemia or frequently
    elevated postprandial glucose).

g.  Eli Lilly will be phasing out all Iletin I (beef/pork) insulins
    by 1999. Iletin II (pork only) will continue to be available.
    Conversion packets from the manufacturer (call 800-545-5979) are
    available to clinicians wishing to convert patients from Iletin I to
    human insulin.

EVIDENCE

Anderson et al., 1997 LE = A; Abraira et al., 1998 LE = B; Buse et al.,
1998. LE = B; Chiasson et al., 1994. LE = B; Chow et al., 1995. LE = B;
Giugliano et al., 1993. LE = B; Johnson et al., 1996. LE = A; Kelley et
al., 1998. LE = B; Robinson et al., 1998. LE = B; Schwartz et al., 1998.
LE = A; Soneru 1993. LE = C; Wolffenbuttel et al., 1996. LE = B;
Yki-Jarvinen et al., 1992. LE = B; Yki-Jarvinen et al., 1999. LE = B

## Alpha-glucosidase inhibitors (Miglitol, Acarbose)

a.  Acarbose is an alpha-glucosidase inhibitor that delays the digestion
    of carbohydrates thereby decreasing postprandial hyperglycemia.

-   Acarbose may be considered for use as monotherapy if a sulfonylurea
    cannot be used (Coniff 1994; Hanefeld 1991; Hoffman 1994;
    Hoffman 1997) It may be used in combination with a sulfonylurea
    (Chiasson 1994), metformin (Chiasson 1994; Rosenstock 1998), or
    insulin (Kelley 1998; Chiasson 1994) in the event of failure with
    monotherapy. The effect of acarbose on glycemic control should be
    additive, due to its different mechanism of action.

-   Acarbose should be considered for patients with elevated
    postprandial plasma glucose, or impaired glucose tolerance.

b.  The efficacy of acarbose in lowering HbA~1~c is inferior to that of
    the oral sulfonylureas and metformin; the general absolute reduction
    in HbA~1~c is 0.5 to 1.0 percent.

c.  Gastrointestinal side effects tend to limit tolerance of acarbose.
    The recommended starting dose is 25mg t.i.d. with the first bite of
    each main meal. However, some patients may benefit from a slower
    titration period (e.g., start at 25 mg per day for 2 weeks, followed
    by 25 mg b.i.d. for 2 weeks, then 25 mg t.i.d. for 8 weeks). Further
    dosage increases may be made at 4 to 8 week intervals. The maximum
    dose is 100 mg t.i.d. (50 mg t.i.d. for patients \< 60 kg).

d.  The patient should be advised of the transient, dose-related GI side
    effects (diarrhea, abdominal pain, and flatulence). Initiating
    therapy at a reduced dosage may reduce these side effects.

e.  Reduction in plasma triglycerides may occur with miglitol use.

f.  If a patient becomes hypoglycemic from a combination of acarbose and
    a hypoglycemic agent, oral glucose (dextrose) should be given to
    treat the reaction, since sucrose (table sugar) or a complex
    carbohydrate (starches) will not be readily effective.

g.  See Table G4g, Acarbose Drug Therapy, for contraindications to the
    use of acarbose.

h.  Discontinue acarbose if glycemic control fails to improve over 3 to
    6 months.

[EVIDENCE]{.smallcaps}

Chiasson et al., 1994 LE = B; Coniff 1994 LE = B; Hanefeld 1991 LE = B;
Hoffman 1994 LE = B; Hoffman 1997 LE = B; Kelley et al., 1998 LE = B;
Rosenstock et al., 1998 LE = B

## 

## Thiazolidinediones (Currently available agents: troglitazone, rosiglitazone)

a.  Thiazolidinediones are believed to enhance insulin sensitivity in
    skeletal, hepatic, and adipose tissue without directly stimulating
    insulin secretion from the pancreas. They also appear to have a
    small effect on inhibiting glucose output.

b.  The efficacy of thiazolidinediones to lower HbA~1~c is no better
    than sulfonylureas or metformin.

> Troglitazone has been associated with severe liver toxicity, is
> expensive, and lacks data, at this time, indicating that patients have
> improved clinical outcomes relative to other therapies. Rosiglitazone
> is also costly and long-term safety and toxicity in general practice
> have not yet been established. For these reasons, thiazolidinediones
> should be used judiciously only in highly selected patients.

[]{.mark}

-   Thiazolidinediones are not recommended as monotherapy.

-   A thiazolidinedione may be used with a sulfonylurea in patients who
    have failed monotherapy with a sulfonylurea (Horton 1998; Iwamoto
    1996). The patient must have failed or have a contraindication to
    using a sulfonylurea in combination with metformin, acarbose or
    insulin (or patient adamantly refuses insulin).

-   A thiazolidinedione may be used in combination with insulin if the
    patient is receiving insulin in doses \> 75 units/day and has a
    HbA~1~c \> 9 percent. (Schwartz 1998; Buse 1998) Patients must have
    failed or have contraindications to both a sulfonylurea/insulin and
    metformin/insulin combination.

c.  The average absolute decrease in HbA~1~c is 0.7 to 1.75 percent when
    given in combination with a sulfonylurea. HbA~1~c should be
    monitored at 3 and at 6 months with significant defined as a \> 1
    percent reduction. Therapy should be discontinued if goals are not
    met.

d.  Liver function tests abnormalities, jaundice, hepatitis, liver
    transplant, and death have been reported therefore, monitoring
    through liver function test is required. This drug should not be
    used if the patient has an ALT \> 1.5x the upper limit of normal.
    See Table G4h, Troglitazone Drug Therapy, for the monitoring
    required when using this drug.

e.  Plasma volumes have been shown to increase with troglitazone
    therapy. Although there has not been an observed increased incidence
    of adverse events potentially relating to volume expansion (e.g.,
    congestive heart failure), patients with New York Heart Association
    Class III or IV have not been included in the clinical trials. Until
    safety data are available, its use in these patients is not
    recommended.

f.  Troglitazone has induced ovulation in premenopausal anovulatory
    patients. This effect has not been established for rosiglitazone.

g.  Increases in low density lipoprotein-cholesterol (LDL-C),
    HDL-cholesterol, total cholesterol, and decrease in triglycerides
    have been observed. Apolipoprotein beta fraction levels are not
    increased.

h.  See Table G4c, Drug Interactions with Oral Hypoglycemic Agents, for
    drug interactions.

[EVIDENCE]{.smallcaps}

Buse et al., 1998. LE = B; Horton et al., 1998. LE= A; Iwamoto et al.,
1996. LE = A; Schwartz et al., 1998. LE = A

## 

## Repaglinide

a.  Repaglinide is a newly marketed oral hypoglycemic agent indicated
    for treatment of type 2 diabetes either as monotherapy (Goldberg
    1998; Wolffenbuttel 1999) or in combination with metformin
    (Moses 1999) for those who failed treatment with either agent alone.
    Like sulfonylureas, it works by stimulating pancreatic secretion of
    insulin.

b.  Repaglinide has a faster onset and shorter duration of action than
    sulfonylureas, therefore postprandial glucose is affected to a
    greater extent than fasting blood glucose.

c.  The effect on HbA~1~c is variable and seems to depend on whether the
    patient has been previously treated with another oral agent.
    Patients previously treated with an oral agent had a HbA~1~c
    reduction of approximately 0.2 to 0.3 percent. Patients not
    previously treated with an oral agent experienced a decrease in
    HbA~1~c of approximately 1.7 to 1.9 percent.

d.  The dose is administered 15 minutes before each meal. Dosing may be
    individualized so that if a patient misses a meal, the corresponding
    dose would be omitted. Repaglinide may be used in patients with
    renal or hepatic impairment; however, dosage adjustments need to be
    made with caution.

The most commonly reported adverse effect of repalinide was hypoglycemia
and was generally comparable to that seen with sulfonylureas.

[EVIDENCE]{.smallcaps}

Goldberg 1998. LE = B; Moses 1999. LE = B; Wolffenbuttel 1999. LE = A

**Table G4a. Drugs That May Impair Glucose Tolerance**

  -----------------------------------------------------------------------
  Beta-blockers, calcium antagonists, diazoxide, diuretics, estrogens,
  glucocorticoids, isoniazid, l-asparaginase, niacin, oral
  contraceptives, pentamidine, phenothiazines, phenytoin, rifampin,
  sympathomimetics, thyroid products.

  -----------------------------------------------------------------------

# Table G4b. Drug Interactions with Oral Hypoglycemic Agents

  ------------------------ ---------------------------------------------------------
  **Sulfonylureas**        There is a potential for drug interactions between
                           sulfonylureas and highly protein bound drugs (e.g.,
                           nonsteroidal anti-inflammatories, salicylates,
                           sulfonamides, chloramphenicol, probenecid, monoamine
                           oxidase inhibitors, tricyclic antidepressants,
                           beta-blockers). These interactions are more likely to
                           occur with the first generation agents. Patients need to
                           be monitored for hypoglycemia or loss of glucose control
                           when these agents are added or withdrawn.

  **Biguanides**           Cationic drugs that are eliminated by renal tubular
                           secretion (e.g. amiloride, digoxin, morphine,
                           procainamide, quinidine, ranitidine, triamterene,
                           trimethoprim, vancomycin) can potentially interact with
                           metformin by competing for elimination by the renal
                           tubular transport system.

  **Thiazolidinediones**   Troglitazone has the potential to induce CYP3A isoenzyme
                           at doses given in clinical practice and may thereby
                           decrease the concentration of drugs metabolized (e.g.
                           cisparide, astemizole, cyclophosphamide, clonazepam,
                           carbamazepine, atorvastatin, amlodipine, cyclosporine) by
                           this enzyme.

  **Repaglinide**          Repaglinide is metabolized by CYP 3A4, therefore drugs
                           which induce (e.g. troglitazone, rifampin, barbiturates)
                           or drugs which inhibit CYP 3A4 (e.g. ketoconazole,
                           erythromycin) may result in a decreased or increased
                           concentration of repaglinide respectively. Repaglinide is
                           also \> 98 percent protein to albumin, therefore other
                           highly protein bound drugs may interact.
  ------------------------ ---------------------------------------------------------

The table below lists interactions that are on file either with the
manufacturer or published in small studies or case reports.

# Table G4c. Interactions with Antidiabetic Agents

+----------------+-----------------+-----------------------------------+
| ######## Anti  | > **Interacting | **Result**                        |
| diabetic Agent | > Drug**        |                                   |
+----------------+-----------------+-----------------------------------+
| Glipizide      | > MgOH or       | Enhanced absorption rate of       |
|                | > NaHCO~3~      | glipizide and glucose reduction   |
|                | > containing    |                                   |
|                | > products      |                                   |
+----------------+-----------------+-----------------------------------+
| Glipizide      | > Fluconazole   | May ↑ glipizide concentration     |
+----------------+-----------------+-----------------------------------+
| Glyburide,     | > Cimetidine    | May ↑ serum concentration of      |
| glipizide      |                 | antidiabetic agent                |
+----------------+-----------------+-----------------------------------+
| Glyburide,     | > Cyclosporine  | May ↑ concentration of            |
| glipizide      |                 | cyclosporine                      |
+----------------+-----------------+-----------------------------------+
| Glyburide      | > Gemfibrozil   | May potentiate action of          |
|                |                 | glyburide                         |
+----------------+-----------------+-----------------------------------+
| Glyburide      | > Rifampin      | May ↓ glyburide concentrations    |
+----------------+-----------------+-----------------------------------+
| Glyburide      | > F             | May potentiate action of          |
|                | luoroquinolones | glyburide                         |
+----------------+-----------------+-----------------------------------+
| Sulfonylureas\ | > Oral          | Can result in hypoglycemia        |
| (unspecified   | > miconazole    |                                   |
| type)          |                 |                                   |
+----------------+-----------------+-----------------------------------+
| Glimepiride    | > Propranolol   | ↑ concentration of glimepiride    |
+----------------+-----------------+-----------------------------------+
| Acarbose       | > Warfarin      | May ↑ absorption of warfarin with |
|                |                 | ↑ INR                             |
+----------------+-----------------+-----------------------------------+
| Acarbose       | > Digestive     | May ↓ effectiveness of acarbose   |
|                | > enzymes       |                                   |
+----------------+-----------------+-----------------------------------+
| Acarbose       | > Digoxin       | Case report of ↓ digoxin          |
|                |                 | concentration                     |
+----------------+-----------------+-----------------------------------+
| Acarbose       | > Charcoal      | May ↓ effectiveness of acarbose   |
|                | > absorbants    |                                   |
+----------------+-----------------+-----------------------------------+
| Metformin      | > Furosemide    | Furosemide may ↑ metformin        |
|                |                 | concentration and metformin may ↓ |
|                |                 | furosemide concentration          |
+----------------+-----------------+-----------------------------------+
| Metformin      | > Nifedipine    | May ↑ concentration of metformin  |
+----------------+-----------------+-----------------------------------+
| Metformin      | > Cimetidine    | May ↑ concentration of metformin  |
+----------------+-----------------+-----------------------------------+
| Troglitazone   | >               | May ↓ absorption of troglitazone  |
|                |  Cholestyramine | by ≈ 70 percent                   |
+----------------+-----------------+-----------------------------------+
| Troglitazone   | > Oral          | Troglitazone can ↓ ethinyl        |
|                | > contraceptive | estradiol and norethindrone       |
|                | > agents        | concentrations                    |
+----------------+-----------------+-----------------------------------+
| Troglitazone   | > Fexofenadine  | May ↓ fexofenadine by 50-70       |
|                |                 | percent                           |
+----------------+-----------------+-----------------------------------+

# Table G4d. Oral Sulfonylureas (a)

+------------+------+-------+----------+---------+---------+---------+
| Su         | Pot  | D     | Daily    | Plasma  | D       | Active  |
| lfonylurea | ency | osing | Dose (b) | ha      | uration | meta    |
|            |      | Int   | (mg/day) | lf-life | of      | bolites |
|            |      | erval |          | (hrs)   | action  |         |
|            |      |       |          |         | (hrs)   |         |
+------------+------+-------+----------+---------+---------+---------+
| **First    |      |       |          |         |         |         |
| Ge         |      |       |          |         |         |         |
| neration** |      |       |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+
| Chlo       | Low  | qd.   | > 100 to | > 36    | > up to | > yes   |
| rpropamide |      |       | > 500    |         | > 60    |         |
+------------+------+-------+----------+---------+---------+---------+
| Tolazamide | Low  | qd.-b | > 100 to | > 7     | > 12 to | > yes   |
|            |      | .i.d. | > 1000   |         | > 24    |         |
+------------+------+-------+----------+---------+---------+---------+
| T          | Low  | b.i   | > 250 to | >       | > 6 to  | > no    |
| olbutamide |      | .d.-t | > 2000   | 4.5-6.5 | > 12    |         |
|            |      | .i.d. |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+
| **Second   |      |       |          |         |         |         |
| Ge         |      |       |          |         |         |         |
| neration** |      |       |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+
| G          | >    | > qd. | 1 to 4   | > 9     | > ≥ 24  | > yes   |
| limepiride | High |       |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+
| Glipizide  | >    | >     | 2.5 to   | > 2 to  | > 10 to | > no    |
| (c)        | High | qd.-b | 20       | > 4     | > 16    |         |
|            |      | .i.d. |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+
| Glipizide  | >    | > qd. | 5 to 10  | > 2 to  | > ≥ 24  | > no    |
| XL         | High |       |          | > 5     |         |         |
+------------+------+-------+----------+---------+---------+---------+
| Glyburide  | >    | >     | 1.25 to  | > 10    | > ≥ 24  | > weak  |
|            | High | qd.-b | 10       |         |         |         |
|            |      | .i.d. |          |         |         |         |
+------------+------+-------+----------+---------+---------+---------+

(a) Hebel 1996:130e-130m

(b) Reflects commonly used doses (maximum dose not shown). The maximum
    daily dose may be necessary for some patients

(c) Absorption is delayed by food, take 30 minutes before a meal.

# Table G4f. Metformin Drug Therapy (a)

+--------------------------------+-------------------------------------+
| ####### Dose                   | #### Cautions/Monitor               |
+--------------------------------+-------------------------------------+
| -   Check S~cr~ and LFTs prior | -   Inform patient to take with     |
|     to starting therapy        |     food to avoid possible GI       |
|                                |     symptoms (diarrhea, nausea,     |
| -   Start 500-850 mg qam with  |     vomiting, bloating, flatulence, |
|     meals                      |     anorexia)                       |
|                                |                                     |
| -   ↑ dosage as needed by      | -   Counsel patient to be aware of  |
|     500-850 mg every 2 weeks   |     possible metallic taste in the  |
|     (split dose b.i.d.)        |     mouth                           |
|                                |                                     |
| -   The usual maintenance dose | -   Monitor BUN, creatinine, and    |
|     is 850 mg b.i.d. with      |     electrolytes within 2 weeks of  |
|     meals                      |     initiation or dosage change     |
|                                |                                     |
| -   Maximum dose: 2550 mg/day  | -   Caution patients against use    |
|     (850mg t.i.d.)             |     with alcohol as alcohol         |
|                                |     potentiates the effects of      |
|                                |     metformin on lactate            |
|                                |     metabolism.                     |
+--------------------------------+-------------------------------------+

\(a\) Adapted from Hebel 1998:130n-130u

# Table G4g. Acarbose Drug Therapy (a) (b)

+---------------------+-----------------------------+------------------+
| ######### **Dose**  | ###                         | ######### **Con  |
|                     | ###### **Cautions/monitor** | traindications** |
+---------------------+-----------------------------+------------------+
| **Initial starting  | -   Inform patient to take  | -                |
| dose:**             |     dose with the first     | Hypersensitivity |
|                     |     bite of each main meal  |     to the drug  |
| > 25 mg t.i.d.      |                             |                  |
|                     | -   Patients should         | -   Presence of  |
| **Alternate         |     maintain a diet high in |     diabetic     |
| starting dose:**    |     complex carbohydrates   |     ketoacidosis |
|                     |     and low in simple       |     or cirrhosis |
| > 25 mg qd. x 1-2   |     sugars to achieve       |                  |
| > weeks             |     maximum benefit and     | -   Presence of  |
| >                   |     minimize adverse        |     intestinal   |
| > followed by 25 mg |     effects                 |                  |
| > b.i.d. for 1-2    |                             |    complications |
| > weeks with        | -   Inform patient of       |                  |
| > subsequent        |     possible GI symptoms    |    (ulcerations, |
| > increase to 25 mg |     (diarrhea, abdominal    |                  |
| > t.i.d. Once a     |     pain, flatulence) that  |    obstructions, |
| > 25mg t.i.d.       |     may occur during the    |     digestion or |
| > dosing regimen is |     first few weeks of      |     absorption   |
| > reached, further  |     therapy                 |     disorders).  |
| > increases may be  |                             |                  |
| > made at a 4-8     | -   Acarbose, especially at |                  |
| > week interval.    |     doses greater than 50   |                  |
|                     |     mg t.i.d., may cause    |                  |
| **Maintenance       |     serum AST/ALT           |                  |
| dosage:**           |     elevation; monitor      |                  |
|                     |     serum levels every 3    |                  |
| > 50 mg t.i.d.      |     months during the first |                  |
|                     |     year of treatment       |                  |
| **Maximum dosage:** |                             |                  |
|                     | -   Renal impairment has    |                  |
| > 100 mg t.i.d.     |     been shown to increase  |                  |
| >                   |     plasma concentrations   |                  |
| > (\< 60 kg 50 mg   |     of acarbose; its use is |                  |
| > t.i.d.)           |     not recommended in      |                  |
|                     |     these patients.         |                  |
+---------------------+-----------------------------+------------------+

(a) Adapted from Hebel 1998:129a-129e

(b) Martin & Montgomery 1996

# Table G4h. Troglitazone Drug Therapy

+---------------------+-----------------------------+-----------------+
| **Dose**            | ###                         | #               |
|                     | ###### **Cautions/Monitor** | ######## **Cont |
|                     |                             | raindications** |
+---------------------+-----------------------------+-----------------+
| -   Current insulin | -   Liver function test     | -   Do not      |
|     dose should be  |     abnormalities,          |     initiate    |
|     continued when  |     jaundice, hepatitis,    |     this drug   |
|     starting        |     liver transplant and    |     in patients |
|     troglitazone.   |     death have been         |     with ALT \> |
|     If using this   |     reported with           |     1.5x the    |
|     drug in         |     troglitazone use.       |     upper limit |
|     combination     |                             |     of normal.  |
|     with a          | -   Liver function tests    |                 |
|     sulfonylurea,   |     and bilirubin should be | -   Plasma      |
|     the current     |     checked every month for |     volume may  |
|     sulfonylurea    |     the first 8 months,     |     increase    |
|     dose should be  |     then every other month  |     with        |
|     continued.      |     for the remainder of    |                 |
|                     |     the first year of       |    troglitazone |
| ```{=html}          |     therapy and             |     thereby     |
| <!-- -->            |     periodically            |     potentially |
| ```                 |     thereafter.             |                 |
| -   Start           |                             |    exacerbating |
|     troglitazone at | -   The patient needs to be |     congestive  |
|     200mg once      |     monitored for signs and |     heart       |
|     daily with a    |     symptoms suggestive of  |     failure.    |
|     meal.           |     hepatic dysfunction     |     Patients    |
|                     |     such as nausea,         |     with New    |
| -   If indicated,   |     vomiting, abdominal     |     York Heart  |
|     the dose may be |     pain, fatigue,          |     Association |
|     increased to    |     anorexia, dark urine or |     Class III   |
|     400mg once      |     jaundice. Patients      |     and IV were |
|     daily after 2   |     should be instructed to |     not         |
|     to 4 weeks. The |     inform their physician  |     included in |
|     maximum dose is |     should they develop     |     clinical    |
|     600mg once      |     these symptoms.         |     trials,     |
|     daily.          |                             |     therefore   |
|                     | -   If ALT is \> 1.5 to 2   |     use in      |
| -   Insulin dosage  |     times the upper limit   |     these       |
|     should be       |     of normal during        |     patients is |
|     decreased by 10 |     therapy, retest ALT     |     not         |
|     to 25 percent   |     within a week then      |                 |
|     after fasting   |     weekly until they       |    recommended. |
|     glucose levels  |     return to normal. If    |                 |
|     decrease to     |     ALT should rise to      |                 |
|     less than       |     about 3x the upper      |                 |
|     120mg/dL.       |     limit of normal,        |                 |
|                     |     discontinue             |                 |
| -   Dosage          |     troglitazone**.**       |                 |
|     adjustment is   |                             |                 |
|     not required in |                             |                 |
|     patients with   |                             |                 |
|     renal           |                             |                 |
|     insufficiency.  |                             |                 |
+---------------------+-----------------------------+-----------------+

# Table G4i. Selected Costs for Type 2 DM Drug Therapy (a)

+--------------------------+--------------+--------------+------------+
| **Drug**                 | **Usual      | **Federal    | #### D     |
|                          | Dose** (b)   | Supply       | APA Prices |
|                          |              | Schedule     |            |
|                          |              | (FSS)        |            |
|                          |              | Cost/Month** |            |
+--------------------------+--------------+--------------+------------+
| **Oral Sulfonylureas**   | > 250 mg     | > \$ 5.82    | > \$ 5.82  |
|                          | > P.O. qd.   | >            | >          |
| *1st Generation:*        | >            | > \$ 2.91    | > \$ 2.82  |
|                          | > 250 mg     | >            | >          |
| > Chlorpropamide         | > P.O.       | > \$ 4.97    | > \$ 5.94  |
| >                        | > b.i.d.     | >            | >          |
| > Tolazamide             | >            | > \$ 7.18    | > \$ 7.20  |
| >                        | > 500 mg     | >            | >          |
| > Tolbutamide            | > P.O.       | > \$ 1.08    | > \$ 1.32  |
|                          | > b.i.d.     | >            | > (c)      |
| *2nd Generation:*        | >            | > \$10.27    | >          |
|                          | > 4 mg P.O.  | >            | > \$ 9.60  |
| > Glimepiride (c)        | > qd.        | > \$ 1.53    | >          |
| >                        | >            |              | > \$ 1.68  |
| > Glipizide (d)          | > 10 mg P.O. |              | > (c)      |
| >                        | > b.i.d.     |              |            |
| > Glipizide XL           | >            |              |            |
| >                        | > 10 mg P.O. |              |            |
| > Glyburide              | > qd.        |              |            |
|                          | >            |              |            |
|                          | > 4 mg P.O.  |              |            |
|                          | > b.i.d.     |              |            |
+--------------------------+--------------+--------------+------------+
| **Insulin**              | > In         | > \$ 5.33    | > \$ 5.30  |
|                          | dividualized | >            | >          |
| > Lente Human - U100/10  | >            | > \$ 15.39   | > \$ 15.31 |
| > mL                     | > In         | >            | >          |
| >                        | dividualized | > \$ 5.33    | > \$ 5.03  |
| > Lispro Human - U100/10 | >            | >            | > (c)      |
| > mL                     | > In         | > \$ 5.33    | >          |
| >                        | dividualized | >            | > \$ 5.24  |
| > NPH Human - U100/10 mL | >            | > \$ 5.33    | > (c)      |
| >                        | > In         | >            | >          |
| > Regular Human -        | dividualized | > \$ 5.33    | > \$ 5.30  |
| > U100/10 mL             | >            |              | >          |
| >                        | > In         |              | > \$ 5.30  |
| > Ultralente Human -     | dividualized |              | > (b)      |
| > U100/10 mL             | >            |              |            |
| >                        | > In         |              |            |
| > 70/30 Human -          | dividualized |              |            |
| > NPH/Regular 10 mL      |              |              |            |
+--------------------------+--------------+--------------+------------+
| **Metformin**            | > 850 mg     | \$ 30.56     | > \$ 45.63 |
|                          | > P.O.       |              | >          |
| **Acarbose**             | > t.i.d.     | \$ 24.00     | > \$ 21.60 |
|                          | >            |              | >          |
| **Troglitazone**         | > 50 mg P.O. | \$ 88.73     | > \$ 88.29 |
|                          | > t.i.d.     |              | >          |
| **Repaglinide**          | >            | \$ 40.13     | > \$ 30.87 |
|                          | > 400 mg     |              | >          |
| **Miglitol**             | > P.O. qd.   | \$ 30.98     | > \$ 30.87 |
|                          | >            |              |            |
|                          | > 1 mg P.O.  |              |            |
|                          | > t.i.d. (d) |              |            |
|                          | >            |              |            |
|                          | > 50 mg P.O. |              |            |
|                          | > t.i.d.     |              |            |
+--------------------------+--------------+--------------+------------+

(a) As of April 1999

(b) Usual dose; does not reflect equivalent doses

(c) DoD Basic Core Formulary (BCF) items. All BSF items are on the DoD
    and Mail Order Pharmacy preferred drug list.

(d) Usual dose not well-determined for this agent; dosing ranges from
    0.5 to 4 mg with each meal.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# Appendix G5. Self Monitoring of Blood Glucose (SMBG)

1.  Patients on stable doses of medications do not need frequent SMBG
    unless the information is being used to alter self-management or
    when providers are considering altering medications. In most cases,
    periodic HbA~1~c is sufficient to ascertain diabetic control.
    (Faas 1997. Oki 1997. Wieland 1997.)

2.  Patients who demonstrate good glycemic control while on a stable
    oral regimen (stable patients) may require fewer or no strips. When
    metabolic control worsens or changes (illness, change in exercise or
    diet, etc.), testing requirements may increase. Each provider must
    ascertain that the patient has proficiency in SMBG technique.
    Initial and ongoing justification for SMBG use must be provided and
    should be linked to health outcomes.

# Table G5 Recommendations for SMBG

+-----------+----------------------------------------------------------+
| **Recomm  |                                                          |
| endations |                                                          |
| for       |                                                          |
| SMBG**    |                                                          |
+===========+==========================================================+
| *         | For stable type 2 DM: No more than 50 strips per 150     |
| *Patients | days. This would allow for twice-weekly testing.         |
| on Oral   | Increased numbers of strips may be needed for a limited  |
| Agents**  | time period for the following indications:               |
|           |                                                          |
|           | -   initiation of therapy and/or active adjustment of    |
|           |     oral agents                                          |
|           |                                                          |
|           | -   prevention and detection of hypoglycemia when        |
|           |     symptoms are suggestive of such, or if documented    |
|           |     hypoglycemia unawareness                             |
|           |                                                          |
|           | ```{=html}                                               |
|           | <!-- -->                                                 |
|           | ```                                                      |
|           | -   detection of hyperglycemia when symptoms or urine    |
|           |     glycosuria (for the occasional patient using urine   |
|           |     test strips) are suggestive.                         |
+-----------+----------------------------------------------------------+
| *         | The frequency of monitoring should be individualized     |
| *Patients | based on the frequency of insulin injections,            |
| on        | hypoglycemic reactions, level of glycemic control, and   |
| Insulin** | patient/provider use of the data to adjust therapy.      |
|           |                                                          |
|           | A combination of pre-and postprandial tests should be    |
|           | performed, up to 4 times per day.                        |
+-----------+----------------------------------------------------------+

EVIDENCE

Faas et al., 1997. LE = B, Oki et al., 1997. LE = C, Wieland et al.,
1997. LE = C

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# References for Module G

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Abraira C; Henderson WG; Colwell JA; Nuttall FQ; Comstock JP; Emanuele
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Silbert CK . Response to intensive therapy steps and to glipizide dose
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American Diabetes Association. Position Statement. Standards of medical
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American Diabetes Association. Report of the expert committee on the
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American Diabetes Association Position Statement. Implications of the
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Anderson JH; Brunell RL; Keohane P; Koivisto VA; Trautmann ME; Vignati
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Bayraktar M; Van Thiel DH; Adalar N. A comparison of acarbose versus
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*Diab Care* 1996; 19:252-54

[]{.mark}

Buse JB; Gumbiner B; Mathias NP; Nelson DM; Faja BW; Whitcomb RW.
Troglitazone use in insulin-treated type 2 diabetic patients*. Diab
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*Diabetes Metab* 1995; 21:256-60

[]{.mark}

Chiasson JL; Josse RG; Hunt JA; Palmason C; Rodger NW; Ross SA; Ryan EA;
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Chow C; Tsang L; Sorensen JP; Cockram CS. Comparison of insulin with or
without continuation of oral hypoglycemic agents in the treatment of
secondary failure in NIDDM patients. *Diab Care* 1995; 18:307-14

Coniff RF; Shapiro JA; Seaton TB. Long-term efficacy and safety of
acarbose in the treatment of obese subjects with non-insulin-dependent
diabetes mellitus. *Arch Intern Med* 1994 Nov 14; 154(21):2442-48

Cusi K; DeFronzo RA. Metformin: a review of its metabolic effects.
*Diabetes Reviews* 1998;6:89-131

DeFronzo R; Goodman A. Multicenter metformin study group. Efficacy of
metformin in patients with non-insulin dependent diabetes mellitus.
*NEJM* 1995;339:541-49

[]{.mark}

Diabetes Control and Complications Research Group (DCCT). The effect of
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[]{.mark}

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VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE H -- HYPERTENSION MANAGEMENT

ALGORITHM AND ANNOTATIONS

![](media/image9.png){width="6.249305555555556in"
height="8.08611111111111in"}

![](media/image10.png){width="6.249305555555556in"
height="8.08611111111111in"}

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

## Module H -- Hypertension Management

# Patient with Diabetes Mellitus and High Blood Pressure (SBP ≥ 140 DBP [\>]{.underline} 85)

definition

Normal blood pressure (BP) for adults is ≤ 130/85 mmHg and high normal
BP is 130-139/85-89 mmHg. There is evidence to suggest that decreasing
BP to ≤ 130/85 mmHg is beneficial in diabetes mellitus (DM), and even
lower BP goals (125/75 mmHg) have been suggested in patients with
proteinuria (\> 1g/24 hours).

**Table H1. Classification of Blood Pressure in Adults** (a)

+-----------------------+----------------------+-----------------------+
| #### Category         | ###### Systolic      | ###### Diastolic      |
+-----------------------+----------------------+-----------------------+
| Normal                | ≤ 130 mmHg *and*     | ≤ 85 mmHg             |
+-----------------------+----------------------+-----------------------+
| High-normal           | 130-139 mmHg *or*    | 85-89 mmHg            |
+-----------------------+----------------------+-----------------------+
| Hypertension (b)      |                      |                       |
+-----------------------+----------------------+-----------------------+
| Stage 1               | 140-159 mmHg *or*    | 90-99 mmHg            |
+-----------------------+----------------------+-----------------------+
| Stage 2               | 160-179 mmHg *or*    | 100-109 mmHg          |
+-----------------------+----------------------+-----------------------+
| Stage 3               | ≥ 180 mmHg *or*      | ≥ 110 mmHg            |
+-----------------------+----------------------+-----------------------+

(a) Adapted from The Sixth Report of the Joint National Committee on
    Detection, Evaluation and Treatment of High Blood Pressure 1997
    (JNC-VI 1997)

(b) Based on the average of two or more readings taken at each of two or
    more visits.

[DISCUSSION]{.smallcaps}

The diagnosis of hypertension is based on the average of two or more
readings taken from the same arm at each of two or more visits in a
person not taking antihypertensive drugs and not acutely ill. When
systolic and diastolic pressure fall into different stages, the higher
should be selected to classify the person's BP status. For instance, a
blood pressure of 160/92 mm Hg should be classified as stage 2, and
180/120 mm Hg as stage 3. Isolated systolic HTN is defined as a systolic
BP of [\>]{.underline}140 mmHg and a diastolic BP of \< 90 mmHg and
staged appropriately (e.g., 170/85 mm Hg is defined as stage 2 isolated
systolic HTN (JNC-VI 1997).

In addition to classifying HTN based on averaged BP levels, the
clinician should rule out the possibility of existing target-organ
disease or the existence of other risk factors. For example, a person
with DM and a BP of 142/94 mm Hg, plus left ventricular hypertrophy
should be classified as having (e.g., stage 1 HTN with target-organ
disease (left ventricular hypertrophy) and other risk factor(s)). This
specificity is important for risk classification and management.

The Sixth Report of the Joint National Committee on Detection,
Evaluation and Treatment of High Blood Pressure includes revised
recommendations for target BP values (\< 130/85 mmHg) in diabetes.
Subsequent studies support a goal blood pressure in diabetes of \<
140/90 mmHg. The Hypertension Optimal Treatment (HOT) Study Group
demonstrated that a progressive reduction of diastolic blood pressure to
85 mm Hg and lower, improves cardiovascular outcomes in people with
diabetes (Hansson, 1998). Similar data were not presented on the effects
of progressively lowering the systolic blood pressure. In the United
Kingdom Prospective Diabetes Study (UKPDS), patients with type 2
diabetes were randomized to receive conventional or tight blood pressure
control. The tight control group with mean blood pressure of 144/82 mmHg
(compared with the conventional group with mean blood pressure of 154/87
mmHg), had significant decrease in both microvascular and cardiovascular
complications (United Kingdom Prospective Diabetes Study 1998). The
initial use of Angiotensin Converting Enzyme (ACE) inhibitor or
beta-blocker was equally effective, and many patients required multiple
drug therapy. Based on this evidence, the panel recommends a target BP
of ≤ 140/85 mmHg in persons with diabetes type 2.

EVIDENCE

Classification of blood pressure in adults has been adapted from the
Sixth Report of the Joint National Committee on Detection, Evaluation
and Treatment of High Blood Pressure 1997. Strength of Recommendation
(SR) = I, Level of Evidence (LE) = C; Hansson et al., 1998; SR = I, LE =
A; United Kingdom Prospective Diabetes Study 1998; SR = I, LE = A

# Is a Secondary Cause Suspected?

OBJECTIVE

To identify patients with an underlying disease process responsible for
their HTN.

ANNOTATION

Although fewer than five percent of all patients have secondary HTN,
clinicians should constantly be alert for secondary causes, as many of
these are reversible (JNC-VI 1977. p. 2419). Secondary HTN should be
suspected for patients with:

-   Abrupt onset of HTN

-   Drug resistant HTN

-   Sudden loss of BP control after a history of good pharmacological
    control

-   Other factors contributors to HTN include substance abuse, diet,
    caffeine, salt, steroids, and psychosocial stressors.

Refer to Annotation I for causes of inadequate response to therapy.

DISCUSSION

**Table H2. Selected Causes and Clinical Features of Secondary
Hypertension** (a)

+------------------+---------------------------------------------------+
| ####### Disease  | ####### Features                                  |
+------------------+---------------------------------------------------+
| Coarctation of   | Delayed or absent femoral pulses and decreased    |
| the aorta        | blood pressure in the legs                        |
+------------------+---------------------------------------------------+
| Cushing's        | Amenorrhea                                        |
| syndrome         |                                                   |
|                  | Buffalo hump                                      |
|                  |                                                   |
|                  | Diabetes mellitus                                 |
|                  |                                                   |
|                  | Edema                                             |
|                  |                                                   |
|                  | Hirsutism                                         |
|                  |                                                   |
|                  | Moon facies                                       |
|                  |                                                   |
|                  | Purple striae                                     |
|                  |                                                   |
|                  | Truncal obesity                                   |
+------------------+---------------------------------------------------+
| Hyp              | Hypercalcemia                                     |
| erparathyroidism |                                                   |
|                  | Polyuria/polydipsia                               |
|                  |                                                   |
|                  | Renal stones                                      |
+------------------+---------------------------------------------------+

(a) JNC-VI 1997.

**Table H2. Selected Causes and Clinical Features of Secondary
Hypertension (a) (Continued)**

+------------------+---------------------------------------------------+
| ####### Disease  | ####### Features                                  |
+------------------+---------------------------------------------------+
| Hyperthyroidism  | Anxiety                                           |
|                  |                                                   |
|                  | Brisk reflexes                                    |
|                  |                                                   |
|                  | Hyperdefecation                                   |
|                  |                                                   |
|                  | Heat intolerance                                  |
|                  |                                                   |
|                  | Tachycardia                                       |
|                  |                                                   |
|                  | Tremor                                            |
|                  |                                                   |
|                  | Weight loss                                       |
|                  |                                                   |
|                  | Wide pulse pressure                               |
+------------------+---------------------------------------------------+
| Hypothyroidism   | Bradycardia                                       |
|                  |                                                   |
|                  | Cold intolerance                                  |
|                  |                                                   |
|                  | Constipation                                      |
|                  |                                                   |
|                  | Fatigue                                           |
|                  |                                                   |
|                  | Goiter                                            |
|                  |                                                   |
|                  | Weight gain                                       |
+------------------+---------------------------------------------------+
| Pheochromocytoma | Labile BP                                         |
|                  |                                                   |
|                  | Most prevalent in young adults                    |
|                  |                                                   |
|                  | Orthostatic hypotension                           |
|                  |                                                   |
|                  | Paroxysms ( headaches, palpitations, sweating,    |
|                  | pallor)                                           |
|                  |                                                   |
|                  | Tachycardia                                       |
+------------------+---------------------------------------------------+
| Primary          | K^+^ ≤ 3.5 mEq/l in patients **not** on diuretic  |
| hy               | therapy; or K^+^ ≤ 3 mEq/l in patients **on**     |
| peraldosteronism | diuretic therapy                                  |
|                  |                                                   |
|                  | Muscle cramps                                     |
|                  |                                                   |
|                  | Polyuria                                          |
|                  |                                                   |
|                  | Weakness                                          |
+------------------+---------------------------------------------------+
| Renal            | Abnormal urine sediment                           |
| parenchymal      |                                                   |
| disease          | Elevated serum creatinine                         |
|                  |                                                   |
|                  | Hematuria on two occasions or structural renal    |
|                  | abnormality (e.g., abdominal or flank masses)     |
|                  |                                                   |
|                  | Recurrent urinary tract infections (UTIs)         |
|                  |                                                   |
|                  | Stones                                            |
+------------------+---------------------------------------------------+
| Renovascular     | Abdominal bruits over the renal arteries          |
| disease          |                                                   |
|                  | Abrupt onset of severe HTN                        |
|                  |                                                   |
|                  | Diastolic BP ≥ 115 mm Hg                          |
|                  |                                                   |
|                  | Initial onset age ≥ 50 years old                  |
|                  |                                                   |
|                  | Signs of arterial narrowing or fundoscopic        |
|                  | abnormalities                                     |
|                  |                                                   |
|                  | Worsening BP control when previously stable       |
+------------------+---------------------------------------------------+
| Sleep apnea      | Chronic Obstructive Pulmonary Disease (COPD)      |
|                  |                                                   |
|                  | Daytime somnolence                                |
|                  |                                                   |
|                  | Fatigue                                           |
|                  |                                                   |
|                  | Obesity                                           |
|                  |                                                   |
|                  | Snoring                                           |
+------------------+---------------------------------------------------+

# Continue Evaluation and Treatment as Indicated. Consider Referral to Appropriate Specialist to Manage Secondary Cause(s)

OBJECTIVE

To detect underlying disease(s) responsible for secondary HTN using
additional laboratory tests.

ANNOTATION

An early discussion or consultation with an appropriate specialist is
encouraged when a patient is suspected of having secondary hypertension.
This may lead to the most accurate and cost-effective workup if an
underlying cause of HTN is suspected.

The following tests may be helpful in determining the need for referral.

##### **Table H3. Recommended Testing for Patients Suspected of Having Secondary Hypertension**

+--------------------+-------------------------------------------------+
| > **Disease**      | > **Recommended Test/Referral**                 |
+--------------------+-------------------------------------------------+
| Cushing's syndrome | > 24- hour urine for free cortisol              |
+--------------------+-------------------------------------------------+
| Hyperaldosteronism | > Serum potassium                               |
+--------------------+-------------------------------------------------+
| H                  | > Serum calcium and parathyroid hormone (PTH)   |
| yperparathyroidism | > level                                         |
+--------------------+-------------------------------------------------+
| Hyperthyroidism/   | > Thyroid Stimulating Hormone (TSH)             |
| Hypothyroidism     |                                                 |
+--------------------+-------------------------------------------------+
| Pheochromocytoma   | > 24-hour urine for metanephrines or urinary    |
|                    | > catecholamines                                |
|                    | >                                               |
|                    | > Consider referral to specialist               |
+--------------------+-------------------------------------------------+
| Renal parenchymal  | > Urinalysis, urine sediment, serum creatinine, |
| disease            | > 24-hour urine for protein and creatinine      |
|                    | > clearance or spot urine for Alb/Cr ratio      |
|                    | >                                               |
|                    | > Consider referral to nephrology               |
+--------------------+-------------------------------------------------+
| Renovascular       | > There are a variety of screening tests for    |
| disease            | > renovascular HTN, depending on equipment and  |
|                    | > expertise in institutions                     |
|                    | >                                               |
|                    | > There is no single best test for renovascular |
|                    | > HTN                                           |
|                    | >                                               |
|                    | > Consult experts in your institution           |
|                    | >                                               |
|                    | > IVPs are relatively contraindicated in        |
|                    | > diabetes                                      |
+--------------------+-------------------------------------------------+
| Sleep apnea        | > Referral for sleep study                      |
+--------------------+-------------------------------------------------+

# Hypertension with End Organ Damage or Strong Indication for Therapy?

OBJECTIVE

To identify manifestations of target organ disease/clinical
cardiovascular disease.

ANNOTATION

Existing target organ damage should be specially investigated in the
following organ systems:

-   Cardiac

-   Cerebrovascular

-   Peripheral vascular

-   Renal (see Module R)

-   Ophthalmic (see Module E).

DISCUSSION

##### **Table H4. Manifestations of Target Organ Disease**

+-------------+--------------------------------------------------------+
| ######## O  | ######## Manifestations                                |
| rgan System |                                                        |
+-------------+--------------------------------------------------------+
| Cardiac     | Clinical, electrocardiographic, or radiological        |
|             | evidence of CAD including angina; *or*                 |
|             |                                                        |
|             | Prior myocardial infarction; *or*                      |
|             |                                                        |
|             | Prior coronary revascularization; *or*                 |
|             |                                                        |
|             | Left ventricular hypertrophy; *or*                     |
|             |                                                        |
|             | "Strain" shown by electrocardiography; *or*            |
|             |                                                        |
|             | Left ventricular dysfunction; *or*                     |
|             |                                                        |
|             | Cardiac failure.                                       |
+-------------+--------------------------------------------------------+
| Cere        | Transient Ischemic Attack (TIA); *or*                  |
| brovascular |                                                        |
|             | Stroke.                                                |
+-------------+--------------------------------------------------------+
| Peripheral  | Absence of one or more major pulses in extremities     |
| vascular    | (except for dorsalis pedis), with or without           |
| disease     | intermittent claudication; aneurysm.                   |
+-------------+--------------------------------------------------------+
| Renal       | Serum creatinine of [\>]{.underline} 130 μmol/L (1.5   |
| disease     | mg/dL) or albuminuria.                                 |
+-------------+--------------------------------------------------------+
| Ophthalmic  | Hemorrhages or exudates, with or without papilledema.  |
+-------------+--------------------------------------------------------+

# Consider Aggressive Life Style Modification With/Without Drug Therapy

OBJECTIVE

To induce life style modifications that will lower BP.

ANNOTATION

There is evidence that BP can improve with:

-   Smoking cessation

-   Increased physical activity (if sedentary)

-   Limitation of alcohol intake

-   Weight reduction (if obese)

-   Moderation of dietary sodium

-   Stress management.

See Module M, Self-management and Patient Education.

# Measure Blood Pressure at Each Office Visit

OBJECTIVE

To properly monitor BP at each office visit.

ANNOTATION

Blood pressure should be measured at each office visit. When initiating
or changing therapy, blood pressure measurements obtained in alternative
settings (other clinics, pharmacies, home, etc.) may be reviewed and
considered.

When monitoring blood pressure in patients with diabetes, it is
important to check for orthostatic hypotension. Patients with autonomic
neuropathy are at increased risk for developing orthostatic hypotension.
In all patients who have diabetes, blood pressure should be measured
periodically in the supine, sitting, and standing positions.

# Is Blood Pressure Control Adequate?

OBJECTIVE

To assess the effectiveness and tolerability of BP-lowering treatment.

ANNOTATION

The goal of the intervention is to maintain BP at or below 140/90 mmHg.
There is evidence suggesting that achieving a BP [\<]{.underline} 130/85
mm Hg may offer increased benefits. Attaining a lower BP target (125/75
mmHg) is recommended for patients who have proteinuria (\> 1g/24h) or
renal insufficiency. The clinician should monitor for and avoid symptoms
of orthostatic hypotension, congestive heart failure (CHF), angina, or
significantly worsened renal function (JNC-VI 1997).

# Initiate/Continue Drug Therapy 

OBJECTIVE

To lower BP using antihypertensive medication.

ANNOTATION

Lifestyle modifications that can lower blood pressure are described in
Annotation E. For continuous monitoring of blood pressure, see
Annotation F. Many medications are available for the treatment of HTN.

Current recommendations for drug therapy (Estacio et al., 1998) are:

1.  **Angiotensin converting enzyme** **(ACE) inhibitors** (2),
    **beta-blockers, alpha-receptor blockers, diuretics** in low doses
    and **angiotensin 2 receptor antagonists** are preferred because of
    fewer adverse effects on glucose homeostasis, lipid profiles and
    renal function.

2.  **Short-acting dihydropyridine calcium-channel blockers** as
    monotherapy have been reported as associated with increased risk of
    cardiovascular complications, and therefore are not preferred
    first-line agents.

3.  **Beta-blocker** therapy should be considered if coronary artery
    disease is present.

4.  If proteinuria or renal disease is present, use **ACE inhibitors**
    as first-line treatment of HTN.

5.  If congestive heart failure is present, consider **ACE inhibitors**
    and **diuretics**.

6.  If systolic dysfunction is present, use **ACE inhibitors**
    preferentially.

[DISCUSSION]{.smallcaps}

When choosing an antihypertensive medication, the potential adverse
affects of the medication need to be considered. Some of these cautions
are reviewed for each class of medication.

**Thiazides**

-   Monitor serum K^+^ 2 to 4 weeks after initiating therapy or changing
    dose, then q 6 to 12 months

-   Hypokalemia may potentiate digitalis toxicity

-   Monitor for hypotension, especially in the elderly

-   Thiazides may have diminished effect in patients with CrCl
    [\<]{.underline} 40 to 50 mL/min (or S~cr~ ≥ 2.5 mg/dL)

-   Use diuretics cautiously in poorly controlled DM, symptomatic BPH,
    or in patients with increased risk of volume depletion

-   K^+^-sparing combination may be preferred at higher thiazide doses

-   Use hydrochlorothiazide (HCTZ)/triamterene with caution with ACE
    inhibitors and other K^+^-retaining drugs or supplements.

**Thiazide Related** *(indapamide and metolazone)*

-   Not routinely used for HTN

-   Reserve indapamide for patients with CrCl \< 25 mL/min

-   Reserve metolazone for intermittent use as a diuretic adjunct in
    patients with CHF or with a CrCl \< 25 mL/min.

**Loop Diuretics**

-   Not routinely used for HTN

-   Loop diuretics may be most effective in patients with CrCl
    [\<]{.underline} 40 to 50 mL/min (or Scr [\>]{.underline} 2.5 mg/dL)

-   Monitor for hypokalemia and hypotension

-   Higher furosemide doses may be needed for patients with nephrotic
    syndrome

-   Twice-a-day dosing should be considered for patients whose
    hypertension is inadequately controlled.

**Beta-Blockers**

-   As doses of cardioselective agents increase, cardioselectivity
    decreases

-   Monitor for bradycardia, CHF, fatigue, insomnia, cold extremities,
    impotence

-   Monitor pulse rate

-   Beta-blockers may mask symptoms of hypoglycemia

-   Discontinue with slow tapering for 1 week

-   Labetalol and carvedilol may cause postural hypotension; therefore
    standing blood pressure (SBP) should be monitored

-   Labetalol may be used in treatment of cyclosporine-induced HTN

-   Labetalol is often used for severe HTN, and higher doses than stated
    may be needed in certain cases

-   Carvedilol dose titrations should not begin sooner than 7 to 14 days
    after initiation

-   Carvedilol should be given with food to reduce the chance of
    orthostatic effects

-   Agents such as acebutolol and labetalol offer fewer advantages over
    others, but may be necessary in restricted circumstances.

**Calcium Channel Blockers** (CCB)**:** [Dihydropyridines]{.underline}
*(nifedipine, amlodipine, nisoldipine, felodipine, isradipine, and
nicardipine)*

-   Short-acting nifedipine should not be used to treat essential HTN

-   Monitor for adverse effects of dihydropyridines: ankle edema,
    dizziness, flushing, headache

-   With the exception of amlodipine, use cautiously in CHF

-   Short-acting dihydropyridines have been associated with an increased
    risk of cardiovascular complications; this association has not been
    observed with sustained-release preparations.

**Calcium Channel Blockers**: [Non-dihydropyridines]{.underline}
*(verapamil, diltiazem, mibefradil)*

*Verapamil*

-   Verapamil is the preferred CCB for stage 1 HTN

-   Monitor for bradycardia and heart block

-   Contraindicated in:

a.  AV node dysfunction (2nd or 3rd degree heart block)

b.  Systolic CHF

c.  Decreased LV function

-   Doses \> 240 mg/d of verapamil tend to increase side effects with
    minimal added benefit.

*Diltiazem*

-   Long-acting preparations of diltiazem may be used for patients with
    any of the following[:]{.smallcaps}

a.  Atrial arrhythmia

b.  Sinus tachycardia

c.  Angina

d.  Asymptomatic ischemia

-   Monitor heart rate, as diltiazem may decrease sinus rate and cause
    heart block.

**ACE Inhibitors**

-   Monitor for hyperkalemia

-   Obtain baseline serum K^+^, Scr, and BUN, repeat laboratory tests
    within 2 weeks after initiating medication; discontinue ACE
    inhibitor if significant elevation occurs

-   Avoid other K^+^-sparing medications.

**Alpha-Blockers**

-   Initial doses should be given at bedtime to reduce the risk of
    syncope

-   Use cautiously in the elderly due to first dose syncope or dizziness

-   Avoid in volume-depleted patients due to orthostasis

-   Decreases in LDL and increases in HDL are of unknown clinical
    significance.

**Angiotensin II Antagonists** *(losartan, valsartan, irbesartan)*

-   Initiate dose of 25 mg in patients with possible depletion of
    intravascular volume (e.g., diuretic-related) and in hepatic
    impairment

-   Reserve for patients who have an indication for an ACE inhibitor but
    who cannot tolerate it

-   Monitor for hyperkalemia.

**Centrally Acting Beta-Agonists (clonidine, guanabenz, methyldopa)**

-   Taper dose to discontinue, do not discontinue abruptly

-   Antihypertensive effects of the patch are not seen until 2 to 3 days
    after switching from oral; the oral medication should be gradually
    tapered over 2 to 3 days while the patch is first administered

-   Clonidine patches are costly but may be useful in selected patients

-   Monitor for sedation (usually transient) during initial therapy with
    methyldopa or whenever the dose is increased.

**Other Centrally Acting Agents** *(reserpine)*

-   Monitor for sedation, depression, nightmares, tremors, nasal
    congestion

-   Higher doses than listed are associated with depression.

**Direct Vasodilating Agents** *(minoxidil and hydralazine)*

-   Monitor for reflex tachycardia with worsening angina, and for edema

-   With hydralazine monitor for:

a.  Headache

b.  Dose related systemic lupus erythematosus (SLE)

-   With minoxidil monitor for:

a.  Hypertrichosis

b.  Pericardial effusions

-   Minoxidil or hydralazine should be used with diuretic and
    beta-blockers to reduce reflex tachycardia and edema.

EVIDENCE

Estacio et al., 1998; SR = I, LE = A; Tatti el al., 1998; SR = I, LE =
A; Cameau et al., 1997; SR = I, LE = A; Hunninghake et al., 1997; SR =
I, LE = A; JNC-VI 1997. SR = I, LE = C; UKPDS 38, 39 1998. SR = I, LE =
A

# Titrate Initial Drug, Add or Substitute Another Agent. Reassess Adherence, Weight, Alcohol, Acute Life Stresses, and Medical Problems. Reinforce Lifestyle Modification. Consider Referral to Specialist

OBJECTIVE

To identify causes of inadequate response to therapy.

ANNOTATION

If blood pressure control is inadequate, the dose of the initial drug
can be titrated, or an agent from another class of drugs can be added.
If a drug is not well tolerated, substitution of an agent from another
class may be considered.

Poor adherence to antihypertensive therapy remains a major therapeutic
challenge. Aside from simple inadequacy of the chosen agent, the
clinician should consider alternate explanations for inadequate response
to drug therapy. These include medical or psychiatric conditions that
undermine blood pressure control (JNC-VI 1997, Table 13, p 2432)

Poor patient response to the initial drug management strategy should
always lead the primary care provider to explore several important
factors that may explain failure to achieve target blood pressure.

###### Table H5. Causes of Inadequate Response to Therapy

+-----------------------+----------------------------------------------+
| # Cause               | # Response                                   |
+-----------------------+----------------------------------------------+
| Non adherence to      | -   Be aware of signs of patient             |
| therapy               |     non-adherence to antihypertensive        |
|                       |     therapy                                  |
|                       |                                              |
|                       | -   Establish the goal of therapy: to reduce |
|                       |     BP to non hypertensive levels with       |
|                       |     minimal or no adverse effects            |
|                       |                                              |
|                       | -   Educate patients about the disease, and  |
|                       |     involve them and their families in its   |
|                       |     treatment. Have them measure blood       |
|                       |     pressure at home                         |
|                       |                                              |
|                       | -   Maintain contact with patients; consider |
|                       |     telecommunication                        |
|                       |                                              |
|                       | -   Encourage lifestyle modification         |
|                       |                                              |
|                       | -   Integrate pilltaking into routine        |
|                       |     activities of daily living               |
|                       |                                              |
|                       | -   Prescribe medications according to       |
|                       |     pharmacological principles, favoring     |
|                       |     long-acting formulations                 |
|                       |                                              |
|                       | -   Be willing to stop unsuccessful therapy  |
|                       |     and try a different approach             |
|                       |                                              |
|                       | Anticipate adverse effects and adjust        |
|                       | therapy to prevent, minimize or ameliorate   |
|                       | side effects.                                |
+-----------------------+----------------------------------------------+
| Pseudoresistance      | > "White coat" hypertension or office        |
|                       | > elevations                                 |
|                       | >                                            |
|                       | > Pseudohypertension (in older patients)     |
|                       | >                                            |
|                       | > Use of regular cuff on very obese arm      |
+-----------------------+----------------------------------------------+

######  

###### Table H5. Causes of Inadequate Response to Therapy (continued)

+-----------------------+----------------------------------------------+
| Volume overload       | > Excess salt intake                         |
|                       | >                                            |
|                       | > Progressive renal damage (nephrosclerosis) |
|                       | >                                            |
|                       | > Fluid retention from reduction of blood    |
|                       | > pressure                                   |
|                       | >                                            |
|                       | > Inadequate diuretic therapy                |
+-----------------------+----------------------------------------------+
| Drug-related causes   | > Adrenal steroids                           |
|                       | >                                            |
|                       | > Antidepressants                            |
|                       | >                                            |
|                       | > Appetite suppressants                      |
|                       | >                                            |
|                       | > Caffeine                                   |
|                       | >                                            |
|                       | > Cocaine and other illicit drugs            |
|                       | >                                            |
|                       | > Cyclosporine, tacrolimus                   |
|                       | >                                            |
|                       | > Dosage too low                             |
|                       | >                                            |
|                       | > Drug actions and interactions              |
|                       | >                                            |
|                       | > Erythropoietin                             |
|                       | >                                            |
|                       | > Inappropriate combinations                 |
|                       | >                                            |
|                       | > Licorice (as may be found in chewing       |
|                       | > tobacco)                                   |
|                       | >                                            |
|                       | > Nasal decongestants                        |
|                       | >                                            |
|                       | > Nonsteroidal anti-inflammatory drugs       |
|                       | >                                            |
|                       | > Oral contraceptives                        |
|                       | >                                            |
|                       | > Rapid inactivation (e.g., hydralazine)     |
|                       | >                                            |
|                       | > Sympathomimetics                           |
|                       | >                                            |
|                       | > Wrong type of diuretic                     |
+-----------------------+----------------------------------------------+
| Associated conditions | > Anxiety-induced hyperventilation or panic  |
|                       | > attacks                                    |
|                       | >                                            |
|                       | > Chronic pain                               |
|                       | >                                            |
|                       | > Ethanol intake more than 3 oz. (90 ml)/day |
|                       | >                                            |
|                       | > Hyperinsulinemia                           |
|                       | >                                            |
|                       | > Intense vasoconstriction (arteritis)       |
|                       | >                                            |
|                       | > Obesity                                    |
|                       | >                                            |
|                       | > Organic brain syndrome (e.g., memory       |
|                       | > deficit)                                   |
|                       | >                                            |
|                       | > Sleep apnea                                |
|                       | >                                            |
|                       | > Smoking                                    |
+-----------------------+----------------------------------------------+
| Identifiable          | Testing for Patients Suspected of Having     |
| secondary causes of   | Secondary Hypertension (see annotation C)    |
| HTN                   |                                              |
+-----------------------+----------------------------------------------+

The primary care provider should employ measures that assist in
improving patient adherence to treatment (JNC-VI 1997, Table 14, p
2432). Many of these measures are designed to engage the patient in his
or her health.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

**References for Module H**

> American College of Sports Medicine. ACSM's Guidelines for Exercise
> Testing and Prescription. Fifth Edition. Baltimore, MD: Williams &
> Wilkins, 1995
>
> American Heart Association. An Active Partnership for the Health of
> Your Heart. American Heart Association. Dallas: TX, 1990
>
> Byington RP; Furberg CD; Craven TE; Pahor M; Sowers JR. Isradepine in
> prediabetic hypertensive subjects. Diab Care 1998; 21:2103-10
>
> Estacio RO; Jeffers BW; Hiatt WR; Biggerstaff SL; Gifford N; Schrier
> RW. The Effect of Nisoldipine as Compared with Enalapril on
> Cardiovascular Outcomes in Persons with NIDDM and HTN. NEJM 1998;
> 338:645-52
>
> Guidelines Subcommittee. 1999 World Health
> Organization---International Society of Hypertension Guidelines for
> the management of Hypertension. J Hyperten 1999; 17:151-83
>
> Hansson L; Zanchetti A; Carruthers, SG; Dahlof B; Elmfeldt D; Julius
> S; Menard J; Rahn KH; Wedel H; Westerling S for the HOT Study Group.
> Effects of intensive blood-pressure lowering and low-dose aspirin in
> patients with hypertension: principal results of the Hypertension
> Optimal Treatment (HOT) randomized trial. Lancet 1998; 351:1755-62
>
> National High Blood Pressure Education Program Working Group. Report
> on HTN in Diabetes. Hypertension 1994; 23(2):152
>
> Pharmacy Benefits Management---Medical Advisory Panel. The
> Pharmacological Management of Hypertension. VHA PBM-SHG Publication
> No. 96-0003. Hines, IL: Pharmacy Benefits Management Strategic Health
> Group, Veterans Health Administration, Department of Veterans Affairs.
> December 1996
>
> The Sixth Report of the Joint National Committee on Detection,
> Evaluation and Treatment of High Blood Pressure. Arch Int Med 1997;
> 157:2413-46
>
> Tatti P; Pahor M; Byington RP; DiMauro P; Guarisco R; Strollo G;
> Stroll F. Outcome Results of the Fosinopril Versus Amlodipine
> Cardiovascular Events Randomized Trial (FACET) in Persons with
> Hypertension and NIDDM. Diab Care 1998; 21:597-603
>
> United Kingdom Prospective Diabetes Study. UKPDS 38. Tight blood
> pressure control and risk of macrovascular and microvascular
> complications in type 2 diabetes. British Medical Journal 1998;
> 317:703-13
>
> United Kingdom Prospective Diabetes Study. UKPDS 39. Efficacy of
> atenolol and captopril in reducing risk of macrovascular and
> microvascular complications in type 2 diabetes. British Medical
> Journal 1998; 317:713-20
>
> U.S. Department of Health & Human Services. National Health Promotion
> and Disease Prevention Objectives. Health People 2000. Washington,
> DC:, 1991. DHHS (PHS) publication 91-50212
>
> U.S. Preventive Services Task Force. Guide to Clinical Preventive
> Services. Second Ed. Baltimore, MD: Williams & Wilkins, 1996.

VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE E - EYE CARE

ALGORITHM AND ANNOTATIONS

![](media/image11.png)

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

## Module E - Eye Care

# Has Patient\'s Vision Changed Recently? 

OBJECTIVE

To identify patients with diabetes mellitus (DM) in need of urgent
referral to an eye care provider.

ANNOTATION

Any acute change in vision or change in ocular function should prompt an
urgent referral to an eye care provider.

DISCUSSION

Acute changes in vision can be arbitrarily defined as those occurring
within a 48 to 72 hour period. Any acute change may indicate a serious
ocular problem. Visual symptoms clearly associated with fluctuations in
blood glucose level should be distinguished from those that are not.
Patients with symptoms not associated with blood glucose fluctuations
usually require urgent attention. The sudden onset of persistent pain or
diplopia should likewise prompt an urgent referral.

Less acute visual disturbances may not represent an immediate threat to
vision, but the primary care provider should consult with an eye care
provider if he or she is uncertain about the significance of changes in
ocular status.

# Reassess Need for Eye Examination within 1 Year

OBJECTIVE

To establish the timing of the initial ocular evaluation for patients
with early-onset DM.

ANNOTATION

For patients with onset of diabetes prior to the age of 30, the risk for
retinopathy becomes significant after 3 to 5 years of disease.

DISCUSSION

Patients with early-onset diabetes (most persons with type 1 fall into
this category) are unlikely to develop clinically apparent retinopathy
within 3 years after the onset of the disease. The prevalence of
retinopathy rises steadily after 3 years and may exceed 29 percent by
the fifth year (Klein 1984a; Klein 1992b). Ocular involvement is mild in
the early cases, but the severity of retinopathy may progress rapidly.

EVIDENCE

Klein et al., 1984a; 1984b. Strength of Recommendation (SR) = I, Level
of Evidence (LE) = B

# Is Any Ocular Risk Factor Present?

OBJECTIVE

To identify patients at risk for advanced retinopathy or rapid
progression of pre-existing diabetic eye disease.

ANNOTATION

High risk patients present with one or more of the following:

-   DM for 15 years or more

-   Gross proteinuria (≥ 200 μg/min)

-   Dialysis dependent

-   Status post renal transplantation

-   Type 2 DM *and* cardiovascular autonomic neuropathy

-   Lower extremity amputation related to DM

-   History of laser therapy for retinopathy

-   Are diabetic and pregnant.

DISCUSSION

Patients at risk for severe retinopathy are generally those with long
duration of disease and/or significant non- ocular complications.

Duration of disease is most strongly associated with advanced
retinopathy in younger onset individuals (\< 30 years at diagnosis or
type 1). The prevalence of proliferative disease approaches 30 percent
in these patients after 15 years of DM (Klein 1984a; Klein 1992b). The
prevalence continues to rise rapidly after this point and reaches 50
percent for males and 33 percent for females after 19 or 20 years of
disease. Although the risk of proliferative retinopathy is much lower
for individuals with a older onset DM ([\>]{.underline} 30 years at
diagnosis or type 2), the prevalence of retinopathy approaches 75
percent for those on insulin and by 20 years the prevalence of
proliferative disease exceeds 20 percent (Klein 1984b).

Gross proteinuria and lower-extremity amputation are also associated
with advanced stages of retinopathy (Savage 1996; Klein 1993; Mayfield
1996). Although the relationship may not be causal, these patients
typically have longstanding or advanced DM and are likely to have other
evidence of micro- or macrovascular complications. Pregnancy can be
associated with a dramatic and rapid progression of pre-existing
retinopathy (Dibble 1982; Klein 1990; Hemachandra 1995). Pregnant
patients require more frequent examinations as the disease may progress
to sight-threatening retinopathy faster than would otherwise be
expected.

The presence of cardiovascular autonomic neuropathy has been associated
with a several fold increase in the risk for proliferative retinopathy
in patients with type 2 disease (Schmid 1995). This association appears
to persist even when other risk factors are taken into account.

Patients who have undergone laser therapy for retinopathy have
presumably reached the stage of vision-threatening diabetic eye disease.
These patients require close long-term follow-up, and in the absence of
information to the contrary, should be considered at high risk for
vision loss.

Regardless of the presence of other risk factors, glycemic control is
clearly related to the risk for chronic complications and the reduction
in risk (Diabetes Control and Complications Trial Research Group, 1993;
Ohkubo 1995; UK Prospective Diabetes Study Group, 1998). The impact of
glycemic control should be considered for each patient when assessing
duration of disease as a risk factor for advanced retinopathy, and the
physician should consider a lower threshold for high risk status for
patients whose disease is chronically poorly controlled---e.g., mean
glycosylated hemoglobin A (HbA~1~c) ≥ 9.

# Refer for Eye Examination Within 1 Month

OBJECTIVE

To ensure that high risk patients are referred expediently.

ANNOTATION

Patients considered at high risk for ocular complications must be seen
expediently and receive a comprehensive dilated eye examination by an
eye care specialist (ophthalmologist or optometrist) knowledgeable and
experienced in the detection of diabetic eye disease.

DISCUSSION

Risk stratification of patients is an appropriate strategy for
prioritizing the referral of patients to specialty care. It helps
maximize the effectiveness of available resources and encourages the
initiation of early treatment for those most likely to need it. Timely
institution of laser therapy in patients with diabetic retinopathy can
reduce the risk of moderate to severe vision loss by 50 to 90 percent,
but the benefits of treatment may be less dramatic for patients who are
not seen until they have progressed to the most advanced stages of
retinopathy.

A dilated fundus examination is the most sensitive method of detecting
retinopathy (Nathan 1991). The highest sensitivity and specificity are
obtained by fundus photography with interpretation by an experienced
reader (Singer 1992). Fundus examination performed by an experienced eye
care provider using stereoscopic viewing can also yield high detection
rates. Nonmydriatic retinal photography can reveal disease in the
posterior retina with a similar degree of sensitivity, but it may not
show important findings in the peripheral retina. In addition, media
opacities such as cataract may lessen the sensitivity of this technique.
Fundoscopy through an undilated pupil is the least sensitive method for
detecting retinopathy and cannot be recommended as a standard of care.
As patients with DM are at risk for other ocular disorders, neither
fundoscopy nor photographic screening obviates the need of periodic
comprehensive eye examinations.

EVIDENCE

Nathan et al., 1991. SR = I, LE = B

# Is Patient Newly Diagnosed Type 2 DM Or On Insulin Therapy?

OBJECTIVE

To identify high risk patients who have not had a dilated eye
examination within the previous 12 months

ANNOTATION

The inability of symptoms alone to accurately predict the presence or
severity of retinopathy necessitates timely referral to an eye care
provider for patients who have not had a dilated eye examination within
the previous 12 months and who have no established examination schedule.

DISCUSSION

The risk for retinopathy increases with duration of disease for
individuals with type 1 and type 2 diabetes (Klein 1984a; Klein 1992b;
Klein 1984b). Patients who develop retinopathy may have rapid
progression over the course of a year, and a small percentage with even
mild retinopathy will progress to proliferative disease within this
timeframe (Ginsburg 1993).

Those with late onset (age ≥ 30) or type 2 DM appear to have a period of
clinical latency that may last several years. Clinically apparent
retinopathy can develop during this time, and nearly 20 percent of
patients will have some retinopathy at the time of diagnosis (Klein
1992b; Klein 1984b). Although the prevalence of vision threatening
retinopathy at the time of diagnosis is very low in asymptomatic
patients (Klein et al., 1992a), a 3 to 4 percent prevalence of
proliferative retinopathy within the first few years of disease makes
deferral of the initial retinopathy screening an inappropriate strategy
for those who have not had a dilated eye examination for 12 months or
more.

EVIDENCE

Klein et al., 1989. SR = I, LE = B

# Follow-Up Examination Yearly or According to Eye Care Provider-Recommended Schedule

OBJECTIVE

To establish a follow-up interval for patients requiring insulin or
whose disease is not well controlled.

ANNOTATION

Patients who have no evidence of retinopathy on dilated fundus
examination are unlikely to develop vision-threatening disease within a
12-month period.

DISCUSSION

A yearly follow-up schedule is a cost-effective and sensitive strategy
for monitoring the status of patients previously free of retinopathy
(Javitt 1989, 1994; Dasbach 1991). Although some patients will remain
retinopathy free for several years (Morisaki 1994; Chen 1995), the
course of the disease cannot reliably be predicted for any individual
patient. Patients who require insulin for the control of their diabetes
are at higher risk for the development and progression of diabetic
retinopathy (Henricsson 1997; Savage 1997; Agardh 1994; Klein 1994;
Klein. 1989). Similarly, patients whose disease is poorly controlled
have a higher prevalence of retinopathy and are more likely to progress
to a vision threatening stage (Klein 1989; Klein 1995a; Nakagami 1997;
Kim 1998). In light of these associations as well as the relationship of
disease duration to risk for retinopathy, it would appear prudent to
perform yearly fundus examinations on most patients.

Other components of the eye examination need not be repeated on a yearly
basis, except where indicated by coexisting ocular conditions, patient
symptoms, or the presence of risk factors for other disorders requiring
yearly screening.

EVIDENCE

Javitt et al., 1989, 1994; Dasbach 1991. SR = I, LE = B; Morisaki et
al., 1994; Chen et al., 1995. SR = I, LE = B

# Patient has maintained HbA1c \> 8.0 

OBJECTIVE

To identify DM patients who do not require insulin and whose disease is
not controlled.

ANNOTATION

Older onset patients not requiring insulin and who are able to maintain
an HbA~1~c level below 8, are at lower risk than other diabetics to
develop advanced retinopathy.

DISCUSSION

The annual incidence of and rate of progression of retinopathy is lower
for individuals not requiring insulin (Henricsson 1997; Savage 1997;
Agardh 1994; Klein 1994; Klein 1989). The lowest rates are found in
those patients whose disease is also well controlled (Klein 1994; Klein
1995a; Nakagami 1997; Kim 1998). It is probably sufficient to follow
these patients bi-annually as long as they remain free of retinopathy
based on findings from a dilated fundus examination. Ethnicity may be an
additional risk factor for some Native and Mexican Americans,
independent of control. These patients may be best served by annual
screenings. Other ocular conditions, symptoms, or disease risk factors
may warrant a more complete evaluation or examinations at different
intervals from the retinopathy screening.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# Appendix E1. Notes on Diabetic Ocular Disease

Diabetic retinopathy is a microangiopathy characterized by a combination
of retinal vascular incompetence and capillary closure. It is usually
divided into non proliferative and proliferative forms, in large part
dependent upon whether the complications of vascular leakage or closure
predominate.

Non proliferative retinopathy is manifest clinically by the presence of
microaneurysms, hemorrhages, lipid exudates, and retinal edema. Patients
develop microinfarcts, or cotton wool spots, in areas of capillary
constriction. As the non proliferative disease advances, the veins may
take on a beaded appearance or show small kinks or loops. The appearance
of fine intraretinal microvascular anomalies (IRMAs) may be confused
with preretinal neovascularization and often precedes its development.

Proliferative retinopathy occurs when widespread retinal ischemia leads
to the proliferation of newly formed vessels over the surface of the
retina or optic nerve. Vessels involving the optic nerve or immediately
adjacent retina are termed neovascularization at the disc (NVD); vessels
involving the remainder of the fundus are called neovascularizaton
elsewhere (NVE). Vitreous hemorrhage occurs when fibrous tissue
accompanying the new vessels contracts and causes traction on the
retinal surface. The hemorrhage obscures fundus details and causes a
corresponding loss of vision in the involved eye.

Laser therapy has been shown to be highly effective in treating diabetic
retinopathy and preventing vision loss (Ferris 1993). It is applied
focally to areas of vascular leakage to treat macular edema and in
\"scatter\" fashion to large areas of the retina to treat proliferative
retinopathy. It may take several weeks to months for a therapeutic
response to occur and it is not unusual for patients to require multiple
treatment sessions.

The effects of DM on the eye are not limited to diabetic retinopathy.
Glaucoma and cataract occur with increased frequency in individuals with
DM and can cause significant visual impairment if not treated (Klein
1995b; Klein 1994; Ederer 1981; Klein BEK 1993).

Cataract formation, or opacification of the lens, is a normal aging
phenomenon. Cataracts degrade the quality of vision due to by irregular
refraction of light and reduction in the optical clarity of the lens.
These changes produce symptoms of glare, loss of contrast, and blurred
vision. If symptoms become incapacitating or limit normal activity, the
lens is removed and replaced with a prosthetic one. Occasionally,
cataracts require removal due to their obscuration of the fundus view,
thus limiting one\'s ability to appropriately follow and treat
co-existing disorders.

Glaucoma is a progressive optic neuropathy that is associated with loss
of the neural rim of the optic nerve head and a gradual reduction in
peripheral vision. Central vision may also be lost with advanced
disease. Although glaucoma is typically associated with increased
intraocular pressure, a significant minority of patients has noβ
documented ocular hypertension (Bonomi 1998; Sommer 1991). The
overwhelming majority of patients with glaucoma have no specific
symptoms attributable to their disease until it is far advanced, making
periodic screening for glaucoma by an eye care provider an important
management strategy.

Race, age, and family history are important risk factors for glaucoma
(Tielsch 1991; Mason 1989; Tielsch 1994). It is four to five times more
prevalent among blacks than among whites and is the leading cause of
blindness in African Americans. The risk for glaucoma increases with age
and is significant for blacks people age 40 and over and for all
individuals age 60 and over. A history of glaucoma in first-degree
relatives further increases the risk, and siblings of individuals with
glaucoma are at very high risk. An association with diabetes has not
been found by all investigators (Tielsch 1995), but glaucoma is found
with increased frequency in the age groups most often affected by
older-onset diabetes.

Glaucoma can be treated with a variety of topical medications that lower
the intraocular pressure. Beta-blockers are used most frequently, but
while generally safe, they can be associated with the same complications
as systemic beta-blockers. The treatment goal is to lower the
intraocular pressure to a level at which further damage will not occur.
This \"target pressure\" is established based on several criteria but is
generally 30 to 50 percent of the baseline level, or untreated value.
Laser surgery is most often used to supplement medical therapy, while
surgery is usually reserved for patients who require a very low pressure
or who have not responded sufficiently to other therapies.

Diabetes is also a risk factor for retinal venous occlusive disease
(Sperduto 1998). Clinically, this condition may simulate diabetic
retinopathy, but the predominance of hemorrhage and the typical
distribution of the hemorrhagic retinopathy help establish the correct
diagnosis. In addition, venous occlusions rarely present bilaterally,
whereas diabetic retinopathy is typically a bilateral disorder. Macular
edema and neovascularization can complicate venous occlusions but in
most cases can be treated successfully with laser therapy.

Arterial occlusive disease, optic neuropathy, and acute mononeuropathies
are additional ocular abnormalities that are frequently seen in
individuals with diabetes. Diabetes is found in approximately 25 percent
of patients with central retinal artery occlusion (Brown 1982). The
existence of occlusive carotid disease and hypertension in persons with
diabetes may contribute to this association.

Sudden swelling of the optic nerve head can occur in young patients with
type 1 diabetes. It is associated with mild-to-moderate loss of vision
and may involve one or both eyes. The loss of vision helps to
distinguish this entity from papilledema when bilateral. It may
represent a mild form of anterior ischemic optic neuropathy and is
associated with good visual recovery. Classic anterior ischemic optic
neuropathy associated with pallid disk edema and moderate-to-severe
vision loss is not uncommon in older adults, but its occurrence in
individuals under age 45 suggests diabetes (Beri 1987).

Acute mononeuropathies involving the III, IV, or VI nerve are also
associated with diabetes. The III nerve is involved most frequently, but
the pupil is spared 80 percent of the time. The palsy is generally
self-limiting, but other causes for oculomotor nerve weakness should be
considered at the time of initial presentation.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**References for Module E**

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the Incidence of Diabetic Retinopathy in Older Onset Diabetes Mellitus.
*Diabet Med* 1994; 11:273-78

Beri M; Klugman MR; Kohler JA; Hayreh SS. Anterior Ischemic Optic
Neuropathy. VII. Incidence of bilaterality and various influencing
factors. *Ophthalmology* 1987; 94:1020-08

Bonomi L; Marchini G; Marraffa M; Bernardi P; De Franco I; Perfetti S;
Varotto A; Tenna V et al. Prevalence of Glaucoma and Intraocular
Pressure Distribution in a Defined Population: The Egna-Neumarkt Study.
*Ophthalmology* 1998; 105:209-15

Brown GC; Margargal LE. Central Retinal Artery Obstruction and Visual
Acuity. *Ophthalmology* 1982; 89:14-19

Chen Ms; Kao CS; Fu CC; Chen CJ; Tai TY. Incidence and progression of
diabetic retinopathy among non-insulin dependent diabetic subjects: A
4-year follow-up. *Int J Epidermiol* 1995; 4:787-95

Dasbach EJ; Fryback DG; Newcomb PA; Klein R; Klein BE.
Cost-Effectiveness of Strategies for Detecting Diabetic Retinopathy.
*Med Care* 1991; 29:20-39

Diabetes Control and Complications Trial Research Group. The Effect of
Intensive Treatment of Diabetes on the Development and Progression of
Long Term Complications in Insulin-Dependent Diabetes Mellitus. *NEJM*
1993; 329:977-86

Dibble CM; Kochenour NK; Worley RJ; Tyler FH; Swartz M et al. Effect of
Pregnancy on Diabetic Retinopathy. *Obstet Gynecol* 1982; 59:699-704

Ederer F; Hiller R; Taylor HR. Senile Lens Change and Diabetes in Two
Population Studies. *Am J Ophthalmol* 1981; 91:381-95

Ferris FL. How Effective Are Treatments for Diabetic retinopathy? *JAMA*
1993; 269:1290-91

Ginsburg LH; Aiello LM. Diabetic Retinopathy: Classification,
Progression, and Management. Focal Points. *Clinical Modules for
Ophthalmologist* 1993; 11:1-14

Haffner SM; Fong D; Stern MP; Pugh ,JA; et al. Diabetic Retinopathy in
Mexican Americans and Non-Hispanic Whites. *Diabetes* 1988; 37:878-84

Hemachandra A; Ellis D; Lloyd CE; Orchard TJ. The Influence of Pregnancy
on IDDM Complications. *Diab Care* 1995; 18:950-54

Henricsson M; Nilsson A; Jangon L; Groop L. The Effect of Glycemic
Control and the Introduction of Insulin Therapy on Retinopathy in
Non-Insulin Dependent Diabetes Mellitus. *Diabet Med* 1997; 14:123-31

Javitt C; Conner JK; Sommer A. Cost Effectiveness of Current Approaches
to the Control of Retinopathy in Type I Diabetes. *Ophthalmology* 1989;
96: 255-64

Javitt JC; Aiello LP; Chiang Y; Ferris FL 3rd; Canner JK; Greenfield S
et al. Preventive Eye Care in Persons with Diabetes is Cost-Saving to
the Federal Government: Implications for health care reform. *Diab Care*
1994; 17:909-16

Kim H-K; Kim C-H; Kim S-W; Park J-Y. Development and Progression of
Diabetic Retinopathy in Koreans with NIDDM. *Diab Care* 1998; 21:134-38

Klein BEK; Moss SE; Klein R. Effect of Pregnancy on Progression of
Diabetic Retinopathy. *Diabetes Care* 1990; 13:34-40

Klein BEK; Klein R; Wang Q; Moss SE. Older Onset Diabetes and Lens
Opacities: The Beaver Dam Eye Study. *Invest Ophthalmol Vis Sci* 1993;
34:1065

Klein BEK; Klein R; Jensen SC. Open Angle Glaucoma and Older Onset
Diabetes: The Beaver Dam Eye Study, *Ophthalmology* 1994; 101:1173-77

Klein R; Klein BEK; Moss SE; Davis MD; DeMets DL. The Wisconsin Study of
Diabetic Retinopathy II. Prevalence and risk of diabetic retinopathy
when age at diagnosis is less than 30 years. *Arch Ophthalmol* 1984a;
102:520-26

Klein R; Klein BEK; Moss SE; Davis MD; DeMets DL. The Wisconsin Study of
Diabetic Retinopathy III. Prevalence and risk of diabetic retinopathy
when age at diagnosis is 30 or more years. *Arch Ophthalmol* 1984b;
102:527-32

Klein R; Moss SE; Klein BE; Davis MD; DeMets DL. The Wisconsin
Epidemiologic Study of Diabetic Retinopathy. XI. The incidence of
macular edema. *Ophthalmology* 1989; 96:1501-10

Klein R; Klein BEK; Moss SE; Linton KL. The Beaver Dam Eye Study:
Retinopathy in adults with newly discovered and diagnosed diabetes
mellitus. *Ophthalmology* 1992a; 99:58-62

Klein R; Klein BEK; Moss SE. The Epidemiology of Ocular Problems in
Diabetes Mellitus. In: Ferman SS, ed. Ocular Problems in Diabetes
Mellitus. Boston, MA: Blackwell Scientific Publications, 1992b:1-53

Klein R; Moss SE; Klein BEK. Is Gross Proteinuria a Risk Factor for the
Incidence of Proliferative Diabetic Retinopathy? *Ophthalmology* 1993;
100:1140-46

Klein R; Klein BEK; Moss SE; Cruickshanks KJC. The Wisconsin
Epidemiologic Study of Diabetic Retinopathy. XIV: Ten year incidence and
progression of diabetic retinopathy. *Arch Ophthalmol* 1994; 112:1217-28

Klein R. Hyperglycemia and Microvascular and Macrovascular Disease in
Diabetes. Kelly West Lecture, 1994. *Diabetes Care* 1995a;18:258-68

Klein R; Klein BEK. Vision Disorders in Diabetes. In: National Diabetes
Data Group. Diabetes in America. 2nd Edition. Bethesda, MD: National
Institutes of Health, 1995b; 293-38

Lee ET; Lee VS; Kingsley RM; Lee M; et al. Diabetic Retinopathy in
Oklahoma Indians with NIDDM: Incidence and risk factors. *Diabetes Care*
1992; 15:620-27

Mason RP; Kosoko O; Wilson MR; Cowan CL Jr; Gear JC; Ross-Degnan D.
National Survey of the Prevalence and Risk Factors of Glaucoma in St.
Lucia, West Indies. Part I: Prevalence findings. *Ophthalmology* 1989;
96:136-68

Mayfield JA; Reiber GE; Nelson RG; Greene T. A Foot Risk Classification
System to Predict Diabetic Amputation in Pima Indians. *Diabetes Care*
1996; 10:704-09

Morisaki N; Watanabe S; Kobayashi J; Kanzaki T; Takahashi K; Yokote K;
Tezuka M; Tashiro J; Inadera H; Saito Y; et al. Diabetic Controls and
Progression of Retinopathy in Elderly Patients: Five year follow-up
study. *J Am Geriatr Soc* 1994; 42:142-45

Nakagami T; Kawahara R; Hori S; Omori Y. Glycemic Control and Prevention
of Retinopathy in Japanese NIDDM Patients: A 10-year follow--up study.
*Diabetes Care* 1997; 20:621-622

Nathan DM; Fogel HA; Godine JE; Lou P I. Role of Diabetologist in
Evaluating Diabetic Retinopathy. *Diabetes Care* 1991; 14:26-33

Nelson RG; Newman JM; Knowler WC; Sievers ML; Kunzelman CL; Pettitt DJ;
Moffett CD; Teutsch SM; Bennett PH. Incidence of end-stage renal disease
in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.
*Diabetologia* 1988 Oct; 31(10):730-36

Ohkubo Y; Kishikawa H; Araki E; Miyata T; Isami S; Motoyoshi S; Kojima
Y; Furuyoshi N; Shichiri M. Intensive Insulin Therapy Prevents the
Progression of Diabetic Microvascular Complications in Japanese Patients
with Non-Insulin Dependent Diabetes Mellitus: A randomized prospective
6-year study. *Diabetes Res Clin Pract* 1995; 28:103-17

Savage S; Estacio R; Jeffers B; Schrier R. Urinary Albumin Excretion as
a Predictor of Diabetic Retinopathy, Neuropathy, and Cardiovascular
Disease in NIDDM. *Diabetes Care* 1996; 19:1243-48

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Non-Insulin Dependent Diabetic Patients Treated with Insulin versus Oral
Hypoglycemic Agents: A population study. *Proc Assoc Am Physicians*
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Schmid H; Schaan B; Cecconello F; Maestri T. Proliferative Diabetic
Retinopathy is Related to Cardiovascular Autonomic Neuropathy in
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29:163-68

Singer DE; Nathan DM; Fogel HA; Schachat AP. Screening for Diabetic
Retinopathy. *Ann Intern Med* 1992; 116:660-71

Sommer A; Tielsch JM; Katz J; Quigley HA. Relationship Between
Intraocular Pressure and Primary Open Angle Glaucoma Among White and
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109:1090-95

Sperduto RD; Hiller R; Chew E; Seigel D; Blair N; Burton TC; Farber MD;
Gragoudas ES; Haller J; Seddon JM; Yannuzzi LA. Risk Factors for
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*Ophthalmology* 1998; 105:765-71

Tielsch JM; Sommer A; Katz J; Royall RM; Quigley HA; Javitt J. Racial
Variations in the Prevalence of Primary Open-Angle Glaucoma: The
Baltimore Eye Survey. *JAMA* 1991; 266:369-74

Tielsch JM; Katz J; Sommer A; Quigley HA; Javitt JC. Family History and
Risk of Primary Open Angle Glaucoma: The Baltimore Eye Survey. *Arch
Ophthalmol* 1994; 112:69-73

Tielsch JM; Katz J; Quigley HA; Javitt JC; Sommer A. Diabetes,
Intraocular Pressure, and Primary Open-Angle Glaucoma in the Baltimore
Eye Survey. *Ophthalmology* 1995; 102:48-53

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352:837-53

VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE F - FOOT CARE

ALGORITHM AND ANNOTATIONS

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# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**Module F - Foot Care**

##### 

##### **SUMMARY**

The goal of this algorithm is to identify those patients who are at high
risk for the development of foot ulcers and lower extremity amputations.
This is done by performing a foot risk assessment to stratify patients
into either high risk or low risk for LE complications. Once the patient
is identified as being at high risk, the patient is referred to a foot
care specialist for a more intensive follow up plan. This plan includes
patient education, appropriate footwear and other specialty referral as
needed.

#### ANNOTATIONS

# Perform and Document Visual Inspection of Feet

OBJECTIVE

To examine the feet for any grossly abnormal findings.

ANNOTATION

Inspect the feet for:

-   Breaks in the skin

-   Erythema

-   Trauma

-   Pallor on elevation

-   Dependent rubor

-   Changes in the size or shape of the foot

-   Nail deformities

-   Extensive callus

-   Tinea pedis

-   Pitting edema.

# Perform Foot Risk Assessment

OBJECTIVE:

To identify those patients who are at risk for lower extremity (LE)
ulcers and amputations.

ANNOTATION:

The foot risk assessment must be performed and documented at least once
a year. The yearly foot risk assessment includes:

-   Evaluation of the skin for breakdown

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-   Assessment of protective sensation

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-   Evaluation for LE arterial disease

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-   Evaluation for foot deformity

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-   Prior history of ulcers or amputations.

In addition, evaluate the patient's footwear

# Are Any Limb Threatening Conditions Present? 

OBJECTIVE

To be alert for patients that may have a limb-threatening condition that
may require immediate attention, referral and or hospitalization.

ANNOTATION

## Systemic or ascending (worsening) Infection?

> Limb threatening conditions could include signs and symptoms of
> systemic infection including gas gangrene, ascending cellulitis and
> lymphangitis or gangrene.
>
> Although infection is not always clinically apparent, common signs and
> symptoms include periulcer area warmth, erythema, purulent drainage,
> odor and involvement of bone. Pain may or may not be present. There
> may or may not be lymphangitis and lymphadenopathy, fever and white
> blood cell count may or may not be present. Sudden loss of glycemic
> control often heralds serious infections.
>
> EVIDENCE
>
> *Assessment of peripheral vascular disease in diabetes*: Orchard &
> Strandness 1993. SR = IIa, LE = C

## Acute Ischemia or Rest Pain?

> Absence of palpable pedal pulses:
>
> Examine the patient to determine presence of dorsalis pedis and
> posterior tibial pulses. No palpable pulses and signs of acute
> ischemia, e.g., resting pain associated with extreme pallor or
> palpably cold extremities, warrant urgent referral to a vascular
> surgeon.
>
> Acute ischemia or rest pin -- evidence of arterial insufficiency:
>
> Lower limb pain at rest, dusky/blue or purple/black color, gangrene,
> or cold extremity. The pain in the toes or forefoot may be relieved by
> dependency of the limb in the early phases. Assessment is needed for
> prompt vascular/surgical intervention. Acute ischemic or avascular
> foot will "present with" pain, pallor, pulseless, paresthesia and/or
> paralysis.
>
> Claudication:
>
> Severe claudication is determined as pain in the thigh or calf that
> occurs when walking less than 1 block and is relieved by rest.
>
> EVIDENCE
>
> Orchard & Strandess 1993. SR = IIa, LE = C

## Foot Ulceration?

Active foot ulcer: A cutaneous erosion with a loss of epithelium that
extends to or through the dermis, can involve deeper tissue and is
characterized by an inability to self-repair in a timely and orderly
manner.

EVIDENCE

> Reiber et al., 1995. SR = I, LE = C; ADA 1990. SR = IIa, LE = C;
> Eckman et al., 1995. SR = IIa, LE = C; Brodsky et al., 1991. SR = IIa,
> LE = C; Caputo et al., 1994. SR = IIa, LE = C

## Puncture Wound?

> Diabetic patients with puncture wounds can quickly develop severe limb
> threatening complications. A lesion through the epidermis, dermis and
> other tissues caused by a piercing or penetrating object.

## Ingrown Toenail?

> An ingrown toenail presents as a nail plate that has pierced the
> surrounding periungual tissue with associated erythema and drainage or
> an area of thick or discolored callus. The primary care provider
> should consider referral to a podiatrist for excision of infected
> ingrown nails, especially in the case of high risk patients.

EVIDENCE

Giacalone 1997. SR = IIa, LE = B

## Hemorrhagic Callus With or Without Cellulitis?

> The provider must determine if the cellulitis maybe associated with
> callus tissue or necrotic tissue that may obscure an underlying
> ulceration or deeper infection.

The callus tissue must be debrided to properly assess the extent of an
underlying ulceration and possible deeper more serious infection.
Necrotic tissue must also be debrided to help eradicate the infection
and determine the full extent of the infection. These patients should be
referred promptly to a foot care specialist for complete evaluation and
treatment.

# Refer To Appropriate Level Of Care For Evaluation And Treatment 

OBJECTIVE

To determine the appropriate intervention.

ANNOTATION

A foot care specialist is defined as a podiatrist, vascular surgeon,
orthopedic surgeon, or other health care provider with demonstrated
training, competence and licensure in foot care.

If the patient's symptoms limit his or her lifestyle, a vascular
specialist can determine appropriateness of surgical intervention on a
patient-specific basis.

DISCUSSION

The patient with cellulitis that is not complicated by hemorrhagic
callus or necrotic tissue and without systemic signs of infection should
be treated with appropriate antibiotics, off-loading weight from the
affected limb, and aggressive follow up to ensure that the condition
does not become severe.

The patient should be alert to signs and symptoms of systemic infection
to include fever, chills, nausea and vomiting, and elevation in blood
sugars. If the patient manifests any of these symptoms, he/she should
notify the provider immediately. If the infection has not resolved
within 7 days of oral therapy or there is a worsening of the symptoms,
the patient should be admitted to a hospital for appropriate IV
antibiotic therapy.

Once the cellulitis has resolved, the patient should be referred to a
foot care specialist for intensive secondary prevention.

Initial therapy could include antibiotics, wound cleansing, tetanus
prophylaxis (if indicated), and/or same-day referral to foot care
specialist.

> Diabetic patients, especially neuropathic patients, often present late
> for treatment with depth mixed aerobic and anaerobic infections that
> require prompt referral and evaluation by a qualified provider who is
> experienced in the management of this condition.

EVIDENCE

*Justification of vascular procedures based on outcomes of vascular
interventions*. Conte et al., 1995. SR = IIa, LE = C; Currie et al.,
1995. SR = IIa, LE = B; Wolf et al., 1993. SR = IIa, LE = A

Lavery et al., 1995. SR = IIa, LE = C

# Is Patient at High Risk for Foot Problem?

OBJECTIVE

To identify patient at high risk for lower extremity foot ulcers and
amputations.

ANNOTATION

The presence of any of the following characteristics equals high risk:

-   Lack of sensation to Semmes-Weinstein 5.07 monofilament at one or
    more noncallused plantar sites.

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-   Evidence of lower extremity arterial disease:

1.  Absence of both dorsalis pedis and tibialis posterior pulses

2.  Dependent rubor or pallor on elevation

3.  History of rest pain or claudication

4.  Prior history of lower extremity bypass surgery.

-   Foot deformities, specifically hammer toes, claw toe, Charcot\'s
    arthropathy

-   History of foot ulcer or non-traumatic lower extremity amputation at
    any level.

Patient at high risk should be referred to a foot care specialist for a
more intensive treatment plan of in-depth patient education concerning
foot care practices, hygiene and footwear.

EVIDENCE

ADA 1990. SR = IIb, LE = C; Bailey et al., 1985. SR = IIb, LE = C; Birke
et al., 1988. SR = IIa, LE = C; Boyko et al., 1996. SR = IIa, LE = B;
Holewski et al., 1988. SR = IIb, LE = C; Mayfield et al., 1996. SR = I,
LE = B; Rith-Najarian et al., 1992. SR = I, LE = B; Sims 1988. SR = IIa,
LE = C; Pecoraro et al., 1990. SR = I, LE = B

# Is There a Minor Wound or Lesion?

OBJECTIVE

To determine the extent of the injury.

ANNOTATION

Minor lesions or wounds that could possibly be treated by the PCP are
blisters, erosions, and/or minor cuts that do not extend beyond
subcutaneous tissue. Pulses are present, there are no signs of acute
infection, and there is no severe lower limb pain and no sign of a
worsening lesion. An ingrown toenail should be referred to a foot
specialist for evaluation and excision. (See Annotation C5, Ingrown
Toenail.)

# Refer promptly to foot care specialist for complete evaluation and treatment.

OBJECTIVE

To ensure more intensive follow up treatment plan.

ANNOTATION

A foot care specialist is defined as a podiatrist, vascular surgeon,
orthopedic surgeon, and other health care provider with demonstrated
training, competence and licensure in foot care.

Mechanical modalities may include footwear recommendations, and
consideration of a footwear prescription will be based upon the
individual structural and clinical findings. Depth shoes should be
prescribed for a patient with foot deformities and peripheral neuropathy
as they can accept pressure-reducing insoles and accommodate foot
deformities. In-depth shoes usually have soft leather uppers paired with
a crepe or Vibram outsole. Custom-molded shoes are reserved for patients
with foot deformities that cannot be accommodated in a depth shoe.

Persons with diabetes should avoid shoes with hard soles, since they do
little to reduce plantar foot pressures. Running shoes have been shown
to reduce plantar pressures in individuals with diabetes; however, they
may not accommodate foot deformities.

# Perform and Document Patient Education for Preventive Foot Care and Footwear 

OBJECTIVE

To empower the patient to perform proper foot care practices.

ANNOTATION

Patient/Family education for preventive foot care and footwear includes:

-   Daily foot inspection and preventive care

-   Skin, nail and callus care

-   What to report and whom to call regarding any foot injury or
    abnormality

-   Footwear: Reduction of lower extremity clinical abnormalities in
    patients with NIDDM.

DISCUSSION

Begin with an assessment of the patient\'s current self-care practices
including asking, \"Do you do anything special to protect your feet?\"

Patient and family foot education should include the following
components and considerations:

a.  Keep it simple and appropriate for patient\'s educational level

b.  Make it interactive, including demonstrations in washing, drying,
    and inspecting feet; nail cutting; and suitable footwear selection,
    including footwear for temperature extremes

c.  Provide opportunities for the patient to state the need for what are
    basics of daily skin and foot care and preventive measures

d.  Include practice time during the educational session to demonstrate
    and have the patient in return demonstrate safe toenail trimming

e.  Provide repetitive examples of and messages of how care of the feet
    can prevent complications. Include recommendations that distinguish
    minor foot problems and more serious problems that require early or
    immediate professional treatment, together with a name and telephone
    number for prompt assistance.

f.  Make realistic recommendations (appropriate to the patient\'s
    physical and visual capabilities) while personalizing information
    and highlighting key points. This may include referral to home
    health care.

g.  Provide written guidelines in large print and/or graphics that the
    patient can hang in a bathroom as a reference, and reprints of lay
    articles. Patients should be alerted that elevation in blood sugar
    might be a sign of an active or impending infection. Use of a
    night-light or turning on lights when getting up at night may
    prevent foot injuries. Patients should be made aware of potential
    dangers in the home.

h.  For patients with high risk feet, twice-daily inspection in good
    light is recommended, looking for any redness or drainage and
    running the hands over the foot to detect any swelling or increased
    local warmth. Patients with neuropathic fingers may need to enlist
    help or use a mirror to inspect their feet.

i.  Before donning footwear, inspect for torn linings, rough spots, and
    foreign materials, e.g., sand and stones.

j.  Alternating between pairs of shoes during the day is recommended to
    alleviate repetitive local pressure. A minimum of two serviceable
    pairs of shoes, insoles and orthoses are needed.

k.  Educators can utilize numerous publications on patient foot care
    instruction that are free of charge and have no copyright
    restrictions. Among them are:

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1.  Take Charge of Your Diabetes: Prevent Foot Problems

2.  Taking Care of Your Feet

3.  Tips on Good Foot Care from Feet Can Last a Lifetime.

Available through the U.S. Department of Health and Human Services, CDC,
and AADE.

EVIDENCE

Litzelman DK et al., 1993. SR = I, LE = A; ADA 1999. SR = IIa, LE = C;
Cavanagh et al., 1987. SR = IIa,

LE = C; Perry et al., 1995. SR = IIa, LE = C; Perry et al., 1995. SR =
IIa, LE = C; Young et al., 1992. SR = IIa, LE = C; Uccioli et al., 1995.
SR = I, LE = B

*Patient self-foot care instruction*: Barth 1990. SR = I, LE = B; Feste
1991. SR = I, LE = C; Fain 1994. Ahroni et al., 1993. SR = I, LE = C;
Weir GC et al., 1994. SR = I, LE = C

# Perform Visual Inspection And Peripheral Sensation at Each Routine Primary Care Visit

OBJECTIVE

To ensure ongoing screening to identify those patients at risk for lower
extremity ulcers and amputation.

ANNOTATION

Follow-up includes:

-   Yearly foot risk assessment - Every individual with diabetes must
    have had a documented foot risk assessment within the past 12 months
    to determine their risk of lower extremity amputation

-   Visual inspection and peripheral sensation testing at routine
    primary care visits - There is limited information, yet consensus
    exists in the diabetes professional community that visual inspection
    combined with peripheral sensation testing may reveal some occult
    lesions in diabetics. This practice also demonstrates to the patient
    the importance of foot assessment.

# Perform Wound Assessment

OBJECTIVE

To determine character and nature of wound.

ANNOTATION

1.  Review anatomic, physical, and lesion characteristics, including
    determination or circumference, depth, and involvement of deep
    structures.

2.  Assess for signs of infection, including necrosis, sinus tracts,
    exudate, odor, presence of fibrin, and healthy granulation tissue.

3.  Assess surrounding areas for signs of edema, cellulitis, or abscess.

# Provide Local Wound Care, Offload Pressure and Weight as Indicated

OBJECTIVE

To provide care of an uncomplicated minor lesion.

ANNOTATION

The following are simple guidelines for the care of uncomplicated minor
lesions:

-   Provide local wound care: Cleanse wound with saline, remove necrotic
    and callus tissue, apply appropriate dressing and other indicated
    treatments.

-   Offload pressure and weight as indicated: Consider lesion site, and
    then provide pressure relief, e.g., special shoes and insoles, bed
    rest, etc. To avoid further trauma to lesion site by use of
    post-operative shoe, offloading or depressurization footwear based
    on lesions site.

-   Follow up on a specified schedule**:** VA facility specific
    patients, but with active lesions need to be followed at least
    monthly.

-   Review self-management and education module: Reinforce nutritional,
    exercise and self-management. recommendations. Avoid initiation of
    calorie restriction diet for weight loss in patients with foot
    lesions.

-   Provide patient and family education.

-   Refer for foot care assistance as needed for patients unable to do
    local wound care. Educate a family member on local wound care or
    refer the patient to a home health service.

EVIDENCE

ADA 1990. SR = IIa, LE = C; Eckman et al., 1995. SR = IIa, LE = C;
Brodsky 1991. SR = IIa, LE = C; Caputo 1994. SR = IIa, LE = C

# Has Wound Healed Within 4 Weeks?

OBJECTIVE

To determine appropriateness of the treatment outcome.

ANNOTATION

Uncomplicated wounds should heal in a timely fashion. Assess for
appropriate reduction in lesion size and depth and appearance of healthy
granulating tissue, with no evidence of infection.

EVIDENCE

*Progress for Wound Healing*: ADA 1990. SR = IIa, LE = C; ADA 1999. SR =
IIa, LE = B

# Is There a Minor Foot Problem?

OBJECTIVE

Identify minor conditions that could be attended to by the patient
and/or family member.

ANNOTATION

Assess feet for presence onychomycosis, painful corn dry skin, athlete's
foot, minor calluses, uncomplicated nail trimming and proper foot
hygiene.

# Treat as Appropriate

OBJECTIVE

To determine the feasibility of treating the patient at home or in the
office of the primary care provider.

ANNOTATION

Many minor foot problems can be treated by the patient and/or family
members, or primary health care providers without referral to foot care
specialists. If this approach is chosen, it is necessary that the
patient and family members have received appropriate education regarding
preventive foot care.

EVIDENCE

Barth 1991. SR = I, LE = B; Feste 1991. SR = I, LE = C; Fain 1994. SR =
I, LE = C; Ahroni 1993. SR = I, LE = C; Weir et al., 1994. SR = I, LE =
C

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**References for Foot Care**

ADA, Diabetic Foot Care 1990

ADA position statement. Foot care in patients with diabetes mellitus.
*Diab Care* 1990; 19 (supplement)

ADA position statement. Preventive care in people with diabetes. *Diab
Care* 1999; 22 (supplement)

Ahroni J. Teaching foot care creatively and successfully. *Diabetes
Educator* 1993; 19(4):230-34

American Heart Association. An Active Partnership for the Health of Your
Heart. Dallas, TX: American Heart Association, c1990

Bailey TS; Yu HM; Rayfield EJ. Patterns of foot examination in a
diabetic clinic. *AJM* 1985; 78:371-374

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Boyko EJ. A prospective study of risk factors for diabetic foot ulcers.
*Diabetes* 1996; Supplement, 194

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Caputo GM; Cavanagh PR; Ulbrecht JS; Gibbons GW; Karchmer; AU*. N Engl J
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Currie IC. Treatment of intermittent claudication: the impact on quality
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K; Pauker SG. Foot infections in diabetic patients. Decision and
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VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE L -- LIPID CONTROL

ALGORITHM AND ANNOTATIONS

![](media/image14.png)

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**Module L - Lipid Control**

# Patient with Diabetes Mellitus and Dyslipidemia

[OBJECTIVE]{.smallcaps}

To concentrate efforts on those patients likely to benefit from
management of lipids.

[ANNOTATION]{.smallcaps}

Efforts to adjust serum lipid levels should be focused on those who are
likely to live more than 5 years.  

DISCUSSION

Stratification of patients to increase the likelihood of benefit is a
cost-effective way of managing abnormal serum lipids. An abnormal serum
lipid is not itself a disease; its management is aimed at decreasing the
risk of clinical illness. In patients with diabetes mellitus (DM) type
2, one can lower the risk of---but not prevent---certain clinical
outcomes, principally cardiovascular disease (CVD).

In older patients, e.g., 70 years or older, there is no observed
relationship between low density lipoprotein -cholesterol (LDL-C) and
CVD (Krumholz 1994). While a high proportion of all CVD events occur in
the elderly, there are limited prospective clinical trial data on the
elderly population. Furthermore, there are no prospective studies on the
effect of lowering LDL-C in diabetic patients above age 70 years and
thus there is no definitive evidence of decreased cardiovascular
mortality in this age group by treating a raised serum LDL-C, whether
diabetes is present or not.

Nevertheless, some data from subsets of prospective studies suggest that
there is some benefit (decreased CVD events) from treatment of those 70
to 75 years of age. An exception could be made to assess lipid levels in
such patients for possible therapy if they appear younger than their
actual age and are otherwise in good health (Summary of the second
report of the National Cholesterol Education Program (NCEP) Expert Panel
on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults 1993 (NCEP-II 1993)).

In premenopausal women, the CVD risk is low and treatment of abnormal
lipids is likely to give minimal benefit, so drug therapy should
generally be delayed. After menopause, coronary risk progressively
increases to approximate the risk in men. For postmenopausal women with
a very high LDL-C level or multiple risk factors, drug therapy can be
considered; however, use of estrogen replacement therapy may obviate the
need for other drug therapy. Whether specific lipid therapy further
reduces CVD risk, the effectiveness of estrogen therapy has not been
established definitively for women (NCEP-II 1993).

EVIDENCE

*Absence of a relationship between serum cholesterol level and
CHD/mortality above age 70 years.* Krumholz et al., 1994. Strength of
Recommendation (SR) = I, Level of Evidence (LE) = B

*Indication to assess lipid levels in older patients who appear younger
than their actual age and are otherwise in good health* NCEP-II 1993. SR
= IIa, LE = C

# Provide and Document Counseling

[OBJECTIVE]{.smallcaps}

 To promote lifestyle changes that will decrease CVD risk. 

[ANNOTATION]{.smallcaps}

There is reasonable evidence that some interventions lower the risk of
CVD.

DISCUSSION

All diabetics need to be advised on lifestyle changes as a matter of
general health (NCEP-II 1993). Appropriate referral for counseling is
advisable.

There is evidence that CVD risk is improved with: 

-   Smoking cessation

-   A low-fat, low-cholesterol diet

-   Exercise

-   Limitation of alcohol intake to one or two drinks per day

-   Weight loss if overweight

-   Stress management.

It is recognized that changing behavior is difficult. Change may not
occur with the best of intentions and efforts. For example, the success
rates of smoking cessation programs are low (at best 15 to 20 percent
and usually lower); similar data apply to the achievement of significant
weight reduction. Even when the behavior is changeable, the effort and
resources required to bring about a clinically significant change may be
better used in other efforts. Clinical judgement is needed to decide how
much effort is reasonable and when to move on.

Despite these data, some patients do succeed and there is, as yet, no
way to identify them. Thus, reasonable efforts to change behaviors need
to be made when indicated and both the efforts and the results should be
documented.

Also see Module M, Self-Management and Education.

EVIDENCE

*Lifestyle changes reduce risk for CVD*: NCEP-II 1993. SR = I, LE = C

# Obtain Lipid Profile TC/TG/LDL/HDL Measured In Fasting State

[OBJECTIVE]{.smallcaps}

To measure reliably the level of serum lipids when indicated.

[ANNOTATION]{.smallcaps}

Most treatment sites offer a lipid profile that includes reporting the
LDL-C level. The lipid profile should be done at least twice before
using the data to make a therapeutic decision. If the LDL-C measurements
differ by more than 30 mg/dL, a third test should be obtained within one
to eight weeks and the average of the three values used (NCEP-II 1993).
Lipids should not be measured in acutely ill patients or for 1 or 2
months after a hospital discharge, as acute illness can effect an
accurate measurement.

With the results, one can determine whether serum lipids constitute a
significant risk factor for CVD in a patient and set a baseline for
future change if specific therapy is started.

DISCUSSION

The National Cholesterol Education Program (NCEP) recommends setting the
LDL-C goal according to the patient's cardiovascular risk profile. LDL-C
value, total cholesterol (TC), high-density lipoprotein cholesterol
(HDL-C), and triglycerides (TG) are measured, most often by obtaining a
lipid profile after a 10 to 13 hour fast. The main marker of interest,
LDC-C is then calculated from these data using the Friedewald equation
(Friedewald 1972). There are now direct assays for LDL-C, which are
becoming more widely available for clinical laboratories.

Because the TG level is affected by food and food-induced elevations in
TG will affect the accuracy of the calculation of the LDL-C level, the
lipid profile should be done in the fasting state, e.g., 10 to 13 hours
after the last meal. If the Friedewald calculation is used with a TG
value above 400 mg/dL will indicate an artificially low value for LDL-C
will be obtained; such a false negative is misleading. Measurement of
LDL-C by a direct assay method obviates this issue, and represents an
alternative for the assessment of the persistently hypertriglyceridemic
patient. If the sample is inadvertently drawn after a shorter
postprandial time, the values can still be used if the TG level is
[\<]{.underline} 400 mg/dL; however, a fasting value is much preferred
(NCEP-II 1993).

In hospitalized patients, serum lipids are often affected by illness or
its treatment and so will not accurately reflect a patient\'s true lipid
profile. Some cardiologists, however, recommend lipid measurement within
a few hours after admission for an acute MI, based on the idea that it
is important to begin lipid-lowering therapy immediately if LDL-C is
elevated. There is no evidence that waiting a few months for an accurate
value affects the outcome. Therefore, lipids are best measured several
months post-discharge, when the effects of acute illness have
dissipated.

EVIDENCE

NCEP-II 1993. SR = I, LE = C

# Is Triglyceride Level \> 400 mg/dL? 

[OBJECTIVE]{.smallcaps}

To determine whether the TG level is high enough to require specific
attention.

[ANNOTATION]{.smallcaps}

A clearly elevated TG (\> 400 mg/dL) may predispose the diabetic patient
to CVD as well as to pancreatitis, and may require drug therapy if not
manageable by other means.

[DISSCUSION]{.smallcaps}

An elevated serum TG correlates positively with CVD in univariate
analysis of risk, however, they are not correlated when other lipid risk
factors are added to the risk analysis (multivariate analysis). The link
between CVD and TG is therefore complex and not fully understood. TG
levels are classified as normal (\< 200 mg/dL), border-line high (200 to
400 mg/dL), high (\> 400 mg/dL), and very high (\> 1000 mg/dL). The
borderline values of TG (200 to 400 mg/dL) have a reasonable chance of
reverting toward normal after nutrition and lifestyle changes are
implemented. For higher levels of TG (\> 400 mg/dL) drug treatment may
be needed even after nutrition, and lifestyle changes are addressed. A
TG value of 400+ may be a contributing risk factor for CVD, and the risk
of pancreatitis increases as the values approach 1,000 mg/dL. Lower
values of TG (200 to 400 mg/dL) have a reasonable chance of reaching
normal levels after nutrition and lifestyle changes are implemented.

EVIDENCE

*Classification of TG levels*: NCEP-II 1993. SR = I, LE = C

# Optimize Glycemic Control

::: Definition-Term
OBJECTIVE
:::

To assess the effect of glycemic control on the TG level. 

::: Definition-Term
ANNOTATION
:::

Poor glycemic control can cause elevated triglycerides. Better glycemic
control may result in lowering the TG level.

::: Definition-Term
DISCUSSION
:::

In some patients, the serum TG level may be raised solely because of
poor glycemic control (DCCT.1995, 1995; Stone 1997). The way to see
whether this is the case is to improve glycemic control and reassess the
serum TG level after several weeks. See Module G, Glycemic Control, for
specific recommendations and strategies for improved control.

EVIDENCE

Effect of intensive diabetes management on macrovascular events and risk
factors in the DCCT. 1995. SR = I, LE = A; Stone 1997. SR = I, LE = A

# Screen for Alcohol Use

[OBJECTIVE]{.smallcaps}

To determine whether alcohol intake is the cause of an elevated TG
level.

[ANNOTATION]{.smallcaps}

Alcohol intake can be the cause of a high TG level. If alcohol intake is
excessive (more than two drinks per day in men and, more than one drink
per day in women, where a drink is defined as 1 oz of hard liquor, 3.5
oz of wine, or 12 oz of beer), then appropriate counseling needs to be
offered (Stone et al. 1997).

[DISCUSSION]{.smallcaps}

Alcohol excess can raise the TG level and is a common cause of secondary
hyperlipidemia (Stone et al. 1997); efforts should be made to remedy
this cause, if present. Screening for excess alcohol intake can be done
with a standardized instrument (CAGE, MAST, AUDIT, etc). If there is
excess alcohol intake, appropriate counseling (by the provider or via
referral) will be needed.

 EVIDENCE

Stone et al., 1997. SR = I, LE = C

# Is Cardiovascular Disease Present? 

[OBJECTIVE]{.smallcaps}

To determine what the target LDL-C level should be in a patient with
diagnosed CVD and institute the most appropriate medical therapy.

[ANNOTATION]{.smallcaps}

The NCEP-II (1993) recommends a target LDL-C of 100 mg/dl or below for
patients with known cardiovascular disease. No definitive LDL-C goal has
been defined by prospective clinical trials. Several large, randomized,
double-blinded, placebo-controlled studies support the idea that
aggressive lowering of LDL-C in these patients significantly reduces
major coronary events but the absolute level is still under debate.

DISCUSSION

The Scandinavian Simvastatin Survival Study (4S) investigators
randomized 4,444 patients with CVD and total cholesterol levels between
213 and 310 mg/dL to receive placebo or simvastatin for 4.9 to 6.3
years. Simvastatin reduced both coronary mortality by 42 percent (P \<
.00001) and the incidence of all major coronary events by 34 percent.
Only 23 percent of 4S patients on simvastatin reached the NCEP goal of
LDL-C level below 100 mg/dL. The authors suggested that there is no
\"magic number\" to which the LDL should be lowered, and instead
hypothesized that risk reduction is a continuum: each 1 percent
reduction in LDL-C reduces major coronary events by 1.7 percent.

The Cholesterol and Recurrent Events (CARE) study investigated the
effect of pravastatin on patients with known CVD, "average" total
cholesterol levels (under 240), and LDL of 115 to174. Pravastatin
lowered the mean LDL of 139 mg/dL to 97 mg/dL (a 32 percent decrease).
The treated group had a 24-percent lower incidence of major coronary
events; however the reduction in the rate of coronary events was
correlated with the pre-treatment level. Patients with baseline levels
above 150 had a 35 percent reduction in events, patients with a baseline
LDL between 125 and 150 had a 26 percent reduction, but those who had
baseline levels below 125 had a 3 percent increase in events. The
authors wrote that this "...suggests that an LDL cholesterol of 125
mg/dl may be an appropriate lower boundary for a clinically important
influence of the LDL cholesterol level on coronary heart disease." The
authors also stated that percentage reduction in LDL had little
relationship to coronary events.

So what is the right LDL? There is currently no "right" answer and there
may never be one. For now it is important to recognize that diabetics
with CVD have a very high risk for recurrent coronary events. In these
patients, aggressive treatment of all risk factors is crucial.

# Initiate AHA Step II Diet. Provide Education and Life Style Counseling.

[OBJECTIVE]{.smallcaps}

To assess the effect of more intensive nutrition and life style
counseling on elevated lipid levels.

[ANNOTATION]{.smallcaps}

In some patients, extra effort toward changing nutrition and life style
factors may succeed in lowering the LDL-C even when usual efforts at
lifestyle change have not.  

DISCUSSION

A raised LDL-C may respond to more intensive lifestyle counseling and
medical nutritional therapy. More importantly, changes in lifestyle can
decrease the global risk of CHD even without changes in the serum
cholesterol level. For example, an increase in exercise can be quite
helpful in weight control and is of benefit in glycemic control, both of
which may impact on CHD risk.

A referral to a registered dietitian for individualized instruction in
meal planning, lifestyle modifications, and food/drug interactions is
preferred. Here, the main recommendations would include:

-   Adjust goals and/or nutrition prescription

-   Review records and evaluate adherence and understanding of percent
    fat intake and type of fat, protein intake, carbohydrate intake,
    soluble fiber intake, physical activity, alcohol intake, and tobacco
    consumption

-   Provide self-management training and material

-   Assess change in weight, body mass index (BMI), tobacco habit,
    physical activity, medications, and laboratory values

-   Review educational materials on food labeling, recipe modification,
    soluble fiber, weight reduction (if applicable), dining out, and, if
    there are changes in medication, potential food/drug interactions.

-   Assess adherence to American Heart Association (AHA) step I diet

-   For patients with CVD, or when step I diet is unsuccessful,
    instruction in the AHA step II diet is recommended to assist
    achieving the goal LDL-C (NCEP II, 1993).

[EVIDENCE]{.smallcaps}

NCEP-II 1993. SR = I, LE = C

# Consider Drug Therapy or Refer to Lipid Consultant

[OBJECTIVE]{.smallcaps}

To identify factors determining pharmacological management and referral
to a lipid consultant.

[ANNOTATION]{.smallcaps}

Diabetics with dyslipidemia without secondary cause (see annotations N
and O) are candidates for pharmacological management or referral to a
lipid specialist in order to achieve lipid goals. Most patients can be
treated by the primary care provider. However, it remains the
prerogative of the primary care provider to refer the patient if the
provider is not comfortable with the pharmacological options. Once the
decision has been made to use pharmacological therapy, the patient is
essentially committed to a lifetime of drug therapy. The decision,
therefore, must be carefully undertaken.

DISCUSSION

The level of LDL cholesterol (LDL-C) at which cardiovascular disease
(CVD) risk is optimally minimized in diabetics is unknown; for this
reason, advocacy for any level of LDL-C cannot be entirely
evidence-based. There are no prospective randomized intervention trials
comparing CVD endpoints associated with different treatment--induced
target or attained levels of LDL-C in exclusively diabetic study
populations. Several primary and secondary prevention studies (Downs
1998; Shepherd 1995; Pedersen 1994; Sacks 1996; LIPID 1998) have
included diabetic patients, but diabetic subgroup analyses have been
hampered by the relatively small number of these patients and the post
hoc nature of the analyses.

Epidemiological evidence suggests that the risk of a first myocardial
infarction (MI) in diabetics is similar to the risk of second MI in
non-diabetics with known prior infarction (Haffner 1998). This coupled
with the NCEP II recommendation of a target LDL-C \< 100 mg/dL in the
setting of secondary prevention (NCEP-II 1993), has led some authors
(Haffner 1998) and organizations (e.g., ADA 1999) to recommend treating
to a target LDL-C \< 100 mg/dL for all diabetics, regardless of known
coronary disease status. However, given the lack of convincing
prospective interventional trial data, this recommendation should be
considered inferential rather than evidence based. To date, no trial has
been specifically designed to answer the question of whether diabetic
patients or non-diabetics in the primary or secondary prevention
settings, who attain an on treatment LDL-C \<100 mg/dL, have fewer
coronary/atherosclerotic (CVD) events than similar patients treated to
130 mg/dL (Grundy 1998). Some investigators have concluded that no
further benefit is derived from reduction of LDL-C below 125mg/dL, in
the setting of non-diabetic secondary prevention (Sacks 1998), while in
contrast, others have found no evidence of a threshold effect in primary
or secondary prevention (Downs 1998; Pedersen 1998). Based on the
absence of consistent clinical trial data to the contrary, this
guideline established a general goal LDL-C \< 130mg/dL for the diabetic
patient in the setting of primary and secondary CVD prevention. The
general goal still allows the provider and patient to set a lower goal
based on individual risk assessment and clinical judgement.

A number of pharmacological options for achieving a specified LDL-C or
TG goal are available. Hydroxymethylglutaryl coenzyme A (HMG CoA)
reductase inhibitors ("statins") are a class of drug with many
beneficial effects on the lipid profile of diabetics. Statins reduce TC,
LDL-C, and TG while slightly raising HDL-C. At higher doses TG may be
reduced as well. Fibrates (e.g., gemfibrozil) primarily reduce TG and in
some cases increase LDL-C. These drugs may be useful, particularly when
a diabetic patient's dyslipidemia is primarily related to abnormal TG
with the LDL-C level at goal. Niacin reduces TC, LDL-C, and TG and
raises HDL-C; however, it may also interfere with glycemic control. For
selected patients it may have some application. Binding agents like
cholestyramine and colestipol lower TC and LDL-C but have no appreciable
effect on HDL-C; however, they may raise TG. Many diabetics have an
elevated TG and for this reason binding agents are often not used in
these patients. For more detailed information regarding drug therapy,
see Appendix G3 and the VA PBM-MAP guideline for the Pharmacological
Management of Hyperlipidemia at www.dppm.med.va.gov.

# Initiate/Modify Drug Therapy to Decrease Triglycerides

[OBJECTIVE]{.smallcaps}

To lower a clearly raised TG level.

[ANNOTATION]{.smallcaps}

With continued elevation of the serum TG level, pharmacological therapy
to lower TG or referral to a lipid consultant is appropriate.

DISCUSSION

Gemfibrozil is the drug most commonly used to lower the TG in a patient
with DM type 2. Niacin, which is effective in lowering both TG and LDL-C
raised levels, is usually avoided in DM type 2 because of its tendency
to raise the serum glucose. However, this effect is by no means
universal, and some patients do well with niacin; it could be tried with
caution in selected cases. For more information on pharmacological
therapy see Appendix 1 and the VA PBM-MAP guideline for the
Pharmacological Management of Hyperlipidemia at
[www.dppm.med.va.gov]{.underline}

# Evaluate for Potential Complications of Drugs. Reassess Lipid Values at Three and/or Six Months. Readjust Medication if Indicated

[OBJECTIVE]{.smallcaps}

To provide adequate monitoring of drug effects and side effects.

[ANNOTATION]{.smallcaps}

Antilipidemic drugs can have side effects, principally on liver
function. Furthermore, these drugs need to be assessed in relation to
the LDL-C goal.

DISCUSSION

After beginning therapy, one can assess the effect on the LDL-C at three
and six months and adjust the dosage as needed. Because the response of
LDL-C to statin drugs is partly dose dependent, earlier reassessment of
the serum LDL-C at one to three months may help guide therapy. If the
goal is not reached by about six months after raising the dose, then one
can consider changing to a different statin or adding another agent,
such as gemfibrozil, or a low dose of colestipol. Niacin is not usually
recommended to lower serum lipid levels in patients with DM because it
has a tendency to raise the serum glucose concentration. However, it may
be useful in patients who do not respond well to other therapies,
particularly in those with a high level of TG.

To avoid unanticipated side effects, hepatic enzymes are generally
assessed initially and again in 1 to 3 months. Further liver enzyme
measurement may be necessary at 4 to 6 and 8 to 10 months, depending on
the drug regimen (see Appendix G3, Insulin Therapy). Firm data on the
optimum frequency of follow-up lipid profiling do not exist.

Most drug side effects occur in the first few months of therapy. The
most frequent main side effect of concern is hepatic dysfunction. If
there is no drug-related hepatic dysfunction during the first year of
therapy, hepatic enzymes can be reassessed periodically---generally once
or twice a year. Muscle injury due to drugs is rare and is usually
detected by complaints of muscle pain or soreness with concomitant
elevations in muscle enzymes, mainly creatinine kinase. For further
information, see Appendix 1 and the VA PBM-MAP guideline for the
Pharmacological Management of Hyperlipidemia at
[www.dppm.med.va.gov](http://www.dppm.med.va.gov/)

# Reassess Lipids Within One Year

[OBJECTIVE]{.smallcaps}

To follow-up lipid testing when LDL-C is within goal and the TG level is
not clearly raised. 

[ANNOTATION]{.smallcaps}

When the LDL-C level is 130 mg/dL or less and the TG level is not
clearly raised, e.g., \< 400 mg/dL, lipid levels should be reassessed at
least annually.

DISCUSSION

There are no data to indicate the optimum time for reassessing lipid
levels when they are at a reasonable level in terms of CVD risk. The
NCEP recommends annual reassessment of CV risk factors and lipid
profiles for any patient with a LDL-C \> 130 mg/dL or two or more
cardiovascular risk factors (NCEP-II 1993). All diabetics have at least
one cardiovascular risk factor (diabetes itself) and frequently have
multiple risk factors. Annual reassessment of the lipid profile can
easily be incorporated into the routine care of all diabetics. 

EVIDENCE

*Annual reassessment of lipid profiles for any patient with two or more
CVD risk factors:* NCEP-II 1993. SR = I, LE = C

# Is LDL-C \> 130 mg/dL? 

O[BJECTIVE]{.smallcaps}

To determine the LDL-C level above which persons with DM type 2 are
likely to be at increased risk for CVD.

ANNOTATION

This level (\> 130 mg/dL of LDL-C) represents the approximate level at
which patients with DM type 2 may benefit from a lower LDL-C.

[DISCUSSION]{.smallcaps}

There is no precise answer on the level of LDL-C to be used as a target
for patients with DM type 2. For patients who have already had a CVD
event and as secondary prevention, there is established benefit in
lowering the LDL-C level to about 130 mg/dL. There is no further proven
benefit below this level, although NCEP recommends a target of \< 100
mg/dL for patients in the secondary prevention of CVD setting. See
annotation H for further discussion.

One study of patients without DM type 2 showed that after coronary
artery bypass graft (CABG), atheroma progression in the graft was
reduced by attainment of an LDL-C level of 100 mg/dL. This level is also
widely recommended as a goal for all patients with raised LDL-C by the
National Cholesterol Education Program (NCEP). In the CABG study,
however, there was no improvement in clinical end points. Furthermore,
there are no other data to support the recommendation of a goal of 100
mg/dL. Nevertheless, one might aim for a LDL-C value of 100 mg/dL in
those with DM type 2 who have had CABG or who otherwise have known CVD
until better data are available.

# Is Thyroid Stimulating Hormone (TSH) High?

[OBJECTIVE]{.smallcaps}

To detect and, if needed, treat hypothyroidism as a contributor to a
raised LDL-C level.

[ANNOTATION]{.smallcaps}

Hypothyroidism is a known secondary cause for elevated LDL-C. If the
thyroid-stimulating hormone (TSH) level is clearly high, the patient
should be treated for hypothyroidism.

[DISCUSSION]{.smallcaps}

It is known that hypothyroidism raises serum LDL-C. The common condition
of primary hypothyroidism is adequately ruled out by a normal serum TSH
level. The rare condition of secondary hypothyroidism (hypothalamic or
pituitary insufficiency) cannot be excluded by TSH alone; if there is
any clinical suspicion of this condition, serum thyroxine (T~4~) should
be measured. Normal TSH and normal T~4~ effectively rule out the
possibility of secondary hypothyroidism.

Treatment of severe hypothyroidism (manifested by very high TSH and/or
very low T~4~) with oral L-thyroxine replacement often lowers elevated
LDL-C to the normal range; treatment of mild, or "subclinical,"
hypothyroidism has considerably less impact on serum LDL-C. In either
case, serum lipids should be assayed 6 to 8 weeks after normalization of
the serum TSH (or T~4~, in the case of secondary hypothyroidism) to see
if any additional treatment is needed. (Stone et al., 1997; NCEP-II
1993)

EVIDENCE

Stone et al., 1997. SR = I, LE = C; NCEP-II 1993. SR = I, LE = C

# Is Nephrosis Present?

[OBJECTIVE]{.smallcaps}

To determine whether nephrosis is present as a potential cause of an
elevated LDL-C.

[ANNOTATION]{.smallcaps}

Nephrosis is a secondary cause of dyslipidemia and an assessment is
indicated when searching for secondary causes of abnormal lipid levels
(Stone et al., 1997; NCEP-II 1993). Nephrosis is characterized by
excessive urinary protein excretion, which may be detected by routine
\"dipstick\" urine testing. If the test is positive on two occasions, a
quantitative 24-hour measurement of urine protein needs to be done.

[DISCUSSION]{.smallcaps}

If the quantitative assay shows a value in the nephrotic range (\> 3.5
g/day), referral to a nephrologist for further evaluation and management
is appropriate.

Nephrosis may or may not account for a raised LDL-C level but is a
serious matter in itself that needs careful attention. Nephrosis is a
powerful predictor of end-stage renal disease in DM type 1 and is
probably a predictor of eventual renal failure in some patients with DM
type 2 as well. While nephrosis in a patient with type 2 DM is most
likely due to diabetic nephropathy, an assessment for other causes can
best be done by a nephrologist or internist.

EVIDENCE

Stone et al., 1997; NCEP-II 1993. SR = I, LE = C.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

# References for Module L

Avins AL; Browner WS. Lowering risk without lowering cholesterol:
implications for national cholesterol policy. *Ann Intern Med* 1996;
125:502

American Diabetes Association: Clinical Practice Recommendations 1999.
Management of dyslipidemia in adults with diabetes. *Diab Care* 1999;
22:Supplement 1, S56

American Heart Association. An Active Partnership for the Health of Your
Heart. American Heart Association. Dallas, TX:1990

Behounek BD; McGovern ME; Kassler‑Taub KB; Markowitz JS; Bergman M. A
multinational study of the effects of low‑dose pravastatin in patients
with non‑insulin‑dependent diabetes mellitus and hyper-cholesterolemia.
*Clin Cardiol* 1994; 17:558

Campeau L; Knatterud L; Damanski M; Hunninghake DB; White CW; Geller NL;
Rosenberg Y. The effect of aggressive lowering of low density
lipoprotein cholesterol levels and low-dose anticoagulation of
obstructive changes in saphenous-vein coronary-artery bypass grafts.
*NEJM* 1997; 336:153-62

Danese MD; Powe NR; Sawin CT; Ladenson PW. Screening for mild thyroid
failure at the periodic health examination. A decision and
cost‑effective analysis. *JAMA* July, 1996; 276:285-92

Downs JR; et al. for the AFCAPS/TexCAPS Research Group. Primary
prevention of acute coronary events with lovastatin in men and women
with average cholesterol levels. Results of AFCAPS/TexCAPS. *JAMA* 1998;
279:1615-22

Demacker PNM; Toenhake‑Dijkstra H; de Rijke YB; Stalenhoef AF; Stuyt PM;
Williams HL. On the presumed inaccuracy of the Friedewald formula in
hypertriglyceridemic plasma: a role for imprecise analysis? *Clin Chem*
1996; 42:1491-94

DCCT Effect of intensive diabetes management on macrovascular events and
risk factors in the Diabetes Control and Complications Trial (DCCT). *Am
J Cardiol* 1995 May 1; 75(14):894-903

Friedewald WT, Levy RI; Fredrickson DS. Estimation of the concentration
of low-density lipoprotein cholesterol in plasma, without use of the
preparative ultracentrifuge. Clin Chem. 1972 Jun; 18(6):499-502

Garber AM; Browner WS; & the American College of Physicians. Guidelines
for using serum cholesterol, high‑density lipoprotein cholesterol, and
triglyceride levels as screening tests for preventing coronary heart
disease in adults. *Ann Intern Med* 1996; 124:515

Grundy SM. Statin trials and goals of cholesterol-lowering therapy.
*Circulation* 1998; 97:1436-39

Haffner SM. Mortality from coronary heart disease in subjects with type
2 diabetes and in nondiabetic subjects with and without prior myocardial
infarction. *NEJM* 1998; 339:229-34

Kreisberg RA. Cholesterol‑lowering and coronary atherosclerosis: good
news and bad news. *Am J Med* 1996; 101:455

Krolewski AS; Warram JH; Freire MBS. Epidemiology of late diabetic
complications. A basis for the development and evaluation of preventive
programs. *Endocrinol Metab Clin North Amer* 1996; 25:217

Krumholz HM; Seeman TE; Merrill SS; Mendesde Leon CF; Vaccarino V;
Silverman DI; Tsukahara R; Ostfeld AM; Bekman LF. Lack of association
between cholesterol and coronary heart disease mortality and morbidity
and all‑cause mortality in persons older than 70 years. *JAMA* 1994;
272:1335-40

Laakso M. Lipids and lipoproteins as risk factors for coronary heart
disease in non­insulin‑dependent diabetes mellitus. *Ann Med* 1996;
28:341

Marchioli R; Marfisi RM; Carinci F; Tognoni G. Meta‑analysis, clinical
trials, and transferability of research results into practice. The case
of cholesterol‑lowering interventions in the secondary prevention of
coronary heart disease. *Arch Intern Med* 1996; 156:1158-72

Nauck M; Kramer-Guth A; Bartens W; Marz W; Wieland H; Wanner C. Is the
determination of LDL cholesterol according to Friedewald accurate in
CAPD and HD patients? *Clin Nephrol* 1996; 46:319-25

Pedersen TR & the Scandinavian Simvastatin Survival Study Group.
Randomized trial of cholesterol lowering in 4444 patients with coronary
heart disease: the Scandinavian Simvastatin Survival Study (4S).
*Lancet* 1994; 344:1383

Pedersen TR & the Scandinavian Simvbastatin survival Study Group.
Lipoprotein changes and reduction in the incidence of major coronary
heart disease events in the scandinavian simvastatin survival study(4S).
*Circulation* 1998; 97:1453-60

Pharmacy Benefits Management Medical Advisory Panel. The Pharmacological
Management of Hyperlipidemia. VHA PBM-SHG Publication No. 96-0002.
Hines, IL: Pharmacy Benefits Strategic Health Group, Veterans Health
Administration, Department of Veterans Affairs. December 1996.

Pyoralka A; Pedersen TR; Kjekshus J; Faergeman O; Olsson AG;
Thorgeirsson G; The Scandinavian Simvastatin Survival Study (4S) Group.
Cholesterol lowering with simvastatin improves prognosis of diabetic
patients with coronary heart disease. *Diab Care* 1997; 20(4):614-20

Pyorala K; Steiner G. Will correction of dyslipoproteinaemia reduce
coronary heart disease risk in patients with non‑insulin‑de-pendent
diabetes? Need for trial evidence*. Ann Med* 1996; 28:357

Ramsey LE; Haq IU; Jackson PR. Targeting lipid‑lowering drug therapy for
primary prevention of coronary disease: an updated Sheffield table.
*Lancet* 1996; 348:87

Ramsey LE; Haq IU; Jackson PR. The Sheffield table for primary
prevention of coronary heart disease: corrected. *Lancet* 1996; 348:1251

Sacks FM; Pfeffer MA; Moye LA; Rouleau JL; Rutheford JD; Cole TG; Brown
L; Warnica JW; Arnold JM; Wunce S; Davis BR; Braunwald E. The effect of
pravastatin on coronary events after myocardial infarction in patients
with average cholesterol levels. Cholesterol and Recurrent Events Trial
Investigators. *NEJM* 1996; 335:1001

Sacks FM. Relationship between plasma LDL concentrations during
treatment with pravastatin and recurrent coronary events in the
cholesterol and recurrent events trial. *Circulation* 1998; 97:1446-52

Shepherd J; Cobbe SM; Ford I; Isles CG; Lorime AR; MacFarlane PW;
McKillop JH; Packard CJ. Prevention of coronary heart disease with
pravastatin in men with hypercholesterolemia. *NEJM* 1995; 333:1301-07

> Stone NJ. Management of Lipids in Clinical Practice. 1997 Professional
> Communications, Inc. ISBN 1-884735-22-3

Summary of the second report of the National Cholesterol Education
Program (NCEP-II) Expert Panel on Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults. *JAMA* 1993 Jun 16; 269(23):
3015-23

Sweany AE; Shapiro DR; Tate AC; Goldbeg RB; Stein EA. Effects of
simvastatin versus gemfibrozil on lipids and glucose control in patients
with non‑insulin dependent diabetes mellitus control in patients with
non‑insulin dependent diabetes mellitus. *Clin Ther* 1995; 17:186-203

VA PBM-MAP guideline for the Pharmacological Management of
Hyperlipidemia. [www.dppm.med.va.gov](http://www.dppm.med.va.gov/)

Whiting MJ; Shephard MDS; Tallis GA. Measurement of plasma LDL
cholesterol in patients with diabetes. *Diab Care* 1997; 20:12

VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE R - RENAL DISEASE TREATMENT

ALGORITHM AND ANNOTATIONS

![](media/image15.png){width="6.370138888888889in"
height="8.227083333333333in"}

![](media/image16.png){width="6.370138888888889in" height="8.24375in"}

![](media/image17.png){width="6.248611111111111in"
height="8.07013888888889in"}

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

######## Module R - Renal Disease

# Patient with Diabetes Mellitus

OBJECTIVE

To screen for renal disease in patients with diabetes mellitus (DM).

ANNOTATION

Patients with type 1 DM should be screened for renal disease after
puberty and at a minimum of every five years of duration. Patients with
type 2 DM should be screened for renal disease at the time of DM
diagnosis because the onset of type 2 DM occurs on average 10 years
before clinical diagnosis is made.

REFERENCE

Harris MI. 1995.

# Obtain Routine Urinalysis (for assessing proteinuria)

OBJECTIVE

To screen for macroalbuminuria and microhematuria in patients.

ANNOTATION

If the protein level is 1+ or greater on routine urinalysis, the patient
already has macroalbuminuria and using a more sensitive test to check
for microalbuminuria is unnecessary. If the red blood cells (RBC) are \>
4 to 5 per high field (HPF), evaluate appropriately.

On the typical dipstick for routine urinalysis (e.g., Combistix),
protein readings are as follows:

> 1+ = 30 mg/dL
>
> 2+ = 100 mg/dL
>
> 3+ = 300 mg/dL
>
> 4+ = 1,000 mg/dL

# Obtain Serum Creatinine

[OBJECTIVE]{.smallcaps}

To detect presence of significant renal insufficiency.

ANNOTATION

The serum creatinine distinguishes patients with severe from those with
mild to moderate chronic renal insufficiency.

DISCUSSION

The serum creatinine does not rise above the normal range until the
creatinine clearance rate has already declined to less than half of
normal (50 ml/min).

# Figure 1. Creatinine Clearance Plotted Against Serum Creatinine Concentration Graph (1)

![](media/image18.png){width="2.9430555555555555in"
height="4.769444444444445in"}

(1) From Schrier 1976

This graph plots the creatinine clearance against serum creatinine
concentration. It illustrates the lack of sensitivity of the serum
creatinine level as a test for loss of renal function. For every
50-percent reduction in glomerular filtration rate (GFR) (approximated
by the creatinine clearance rate), the serum creatinine concentration
approximately doubles. Waiting to treat aggressively the condition until
the serum creatinine level rises is not likely to prevent end-stage
renal disease dialysis, just delayed for a few more months (Bennett
1995).

# Is Serum Creatinine ≥ 2.0 mg/dL?

OBJECTIVE

To identify individuals with moderate to severe renal insufficiency in
need of immediate evaluation.

ANNOTATION

Serum creatinine [\>]{.underline} 2.0mg/dL indicates a substantial loss
of remaining functional units in the kidney. These individuals may
already be developing secondary complications and be in need of a
nephrologist\'s assessment or co-management. Waiting to treat
nephropathy until the serum creatinine level rises above normal range is
not likely to prevent end-stage renal disease, but rather just delay the
need for dialysis a few more months (Bennett 1995).

# Consider Referral or Consult with Nephrologist/Dietitian

OBJECTIVE

To decide whether referral is needed for either diagnostic or
co-management reasons.

ANNOTATION

Referral to or consultation by telephone with a nephrologist may be
helpful to the primary care physician to jointly manage:

-   Electrolyte disorders (hyperkalemia, acidosis)

-   Secondary hyperparathyroidism

-   Anemia secondary to erythropoietin deficiency

-   Fluid overload

-   Preparation for dialysis access, including development of forearm
    muscle mass and preservation of vascular access site (no needle
    sticks)

-   Immunizations, including Heptovax.

There also is a need to treat high blood pressure aggressively and to
lower potassium and protein content of the diet to delay the need for
dialysis Without intervention, progression to end-stage renal disease
can occur rapidly. In addition, reversible causes of elevated creatinine
need to be investigated, such as urinary tract obstruction or acute
glomerulonephritis. The nephrologist can be consulted to assist in this
workup. If a telephone consultation is used, it is advisable to document
the conversation in the patient\'s medical record (Bennett 1995).

REFERENCE

Bennett et al., 1995.

# Is Serum Creatinine \> 1.4 but \< 2.0 mg/dL? 

OBJECTIVE

To identify individuals with moderate renal insufficiency in need of
further diagnostic workup.

ANNOTATION

Patients with a serum creatinine level between 1.4 and 2.0 mg/dL also
have significant renal disease but are less likely to have electrolyte
disturbances, anemia, or bone disease than those with a creatinine level
of ≥ 2.0 mg/dL. If diabetic nephropathy is the cause of the elevated
creatinine, the patient is likely to have all of the following:

-   Macroalbuminuria (≥ 300 mg/24 hours)

-   Some evidence of diabetic retinopathy

-   Normal size kidneys.

With regard to the natural history of the disease, even if the patient
was not previously hypertensive, his or her blood pressure is likely to
begin increasing at this stage. If proteinuria is in the nephrotic range
(\> 3g/24 hours), the patient may also develop peripheral edema or
anasarca (Bennett 1995).

REFERENCE

American Diabetes Association 1997. SR = IIa, LE = C; Bennett et al.,
1995. SR = IIa, LE = C

# Identify and Treat Transient Causes of Proteinuria

OBJECTIVE

To identify and treat potential non-diabetic causes of proteinuria.

ANNOTATION

\"Heavy exercise, urinary tract infection, acute febrile illnesses, and
heart failure may transiently increase urinary albumin excretion and
thus, screening should be postponed in these situations.\" (American
Diabetes Association 1997; Bennett et al., 1995). This Panel does not
recommend stopping an ACE (angiotensin-converting enzyme) inhibitor in
screened patients already being treated with this medication. This Panel
recommends instructing patients not to exercise the day before providing
a specimen.

#### Table R1. Factors that Transiently Interfere with Urinary Screening for Albuminuria

+----------------------------------------+-----------------------------+
| **Increases in Albuminuria**           | # Decreases in Albuminuria  |
+----------------------------------------+-----------------------------+
| Blood in urine                         | ACE inhibitors              |
|                                        |                             |
| Congestive heart failure               | Malnutrition                |
|                                        |                             |
| Exercise                               | Nonsteroidal                |
|                                        | anti-inflammatory drugs     |
| Excessive protein intake               | (NSAID)                     |
|                                        |                             |
| Fever                                  |                             |
|                                        |                             |
| Uncontrolled diabetes                  |                             |
|                                        |                             |
| Uncontrolled hypertension              |                             |
|                                        |                             |
| Urinary tract infection                |                             |
|                                        |                             |
| Vaginal fluid contamination of         |                             |
| specimen                               |                             |
|                                        |                             |
| NSAIDs                                 |                             |
+----------------------------------------+-----------------------------+

EVIDENCE

American Diabetes Association 1996. SR = I, LE = C; Bennett et al.,
1995. SR = I, LE = C

# Is Probable Life Expectancy ≥ 5 Years?

OBJECTIVE

To determine if patients with proteinuria are likely to live long enough
to develop renal disease.

ANNOTATION

Diabetic nephropathy develops 5 to 20 years after the diagnosis of DM.
Patients who do not already have proteinuria are not likely to develop
end-stage renal disease in less than 5 years.

DISCUSSION

\"If left untreated (persistent albuminuria of ≥ 300 mg/24 hours), renal
disease eventually leads to uremia and death after approximately 7 to 10
years.\" (ADA 1997) However, this prognosis can be modified through
early intervention. In patients with type 2 DM, microalbuminuria (30-300
mg/24 hours) is a less specific marker or development of overt diabetic
nephropathy, and end-stage renal disease (ESRD), at least in part of the
higher death rate from coronary artery diseases). Twenty to 25 percent
of patients with type 2 DM and microalbuminuria, eventually develop
ESRD, compared with 80 percent of type 1 DM patients. This discrepancy
has been primarily attributed to premature cardiovascular mortality
among type 2 DM patients (Mogensen 1987). Patients who have multiple
comorbidities, e.g., congestive heart failure (CHF), metastatic cancer,
dementia, etc., are likely to have a shortened life expectancy. The
natural history of diabetic nephropathy substantiates the following
outcome: patients with a life expectancy of less than five years without
proteinuria, are likely to die before they develop significant diabetic
renal disease. Therefore, at least once a year the provider should
reevaluate the patient\'s life expectancy. If it has increased
significantly from the previous year (due to improvements in
comorbidities), the appropriateness of screening for nephropathy should
be revisited (Bennet 1995; Mogensen 1987; Gall 1991; Ordonez 1989).

EVIDENCE

Bennet et al., 1995. SR = IIa, LE = C; Mogensen 1987. SR = IIa, LE = C;
Gall 1991. SR = IIa, LE = C; Ordonez 1989. SR = IIa, LE = C

# Measure Spot Urine for Albumin and Creatinine

OBJECTIVE

To screen for early nephropathy.

ANNOTATION

Either random urine testing for albumin-to-creatinine ratio or timed
urine testing can identify the presence of microalbuminuria. For random
urine testing, the optimal collection time is the first urination of the
morning. Strips are available to detect albuminuria as low as 20 mg/L
but are not the recommended method, because they do not take into
account possible errors resulting from alterations in urine
concentration (Kouri 1991). Listed below are cutpoints for the various
specimen types adopted from the American Diabetes Association.

DISCUSSION

##### 

# Table R2. Diagnosis of Proteinuria in Diabetes Mellitus

  ---------------------- ----------------- ----------------- -----------------
  **Condition**          **24-Hour Urine   **Alb/Cr**        **Timed Urine
                         Collection**                        Collection**

  **Normal albuminuria** ≤ 30 mg/24h       \< 30 mg/g        ≤ 20 µg/min
                                           creatinine        

  **Microalbuminuria**   30-300 mg/24h     30-300 mg/g       20-200 µg/min
                                           creatinine        

  **Macroalbuminuria**   ≥ 300 mg/24h      ≥ 300 mg/g        ≥ 200 µg/min
                                           creatinine        
  ---------------------- ----------------- ----------------- -----------------

EVIDENCE

Kouri 1991. SR = III, LE = B

# Is Urine Alb/Cr ≥ 30 mg/g Confirmed?

OBJECTIVE

To establish a diagnosis of early diabetic nephropathy and to ensure
that albuminuria is persistent, not transient, before committing the
patient to treatment.

ANNOTATION

This cutpoint represents microalbuminuria. If the first specimen is ≥ 30
mg/g, repeat the test and be sure to have addressed the factors that may
have transiently elevated the urine\'s albumin (see Annotation G). If
the second specimen is also ≥ 30 mg/g, the patient has persistent
microalbuminuria. If the second test is \< 30 mg/g, repeat the test a
third time. \"Multiple urinary measurements are necessary because as
much as a 30 to 50 percent variability in day-to-day urine microalbumin
measurements may occur.\" (Murray 1996)

EVIDENCE

Murray 1996. SR = I, LE = C

# Check 24-Hour Urine for Creatinine and Protein or Random Urine for Protein/Cr Ratio or Alb/Cr Ratio

OBJECTIVE

To quantify the amount of proteinuria and to estimate the creatinine
clearance rate.

ANNOTATION

The creatinine clearance rate approximates the GFR, but because of
variability in collection, it is no more accurate than the commonly used
Cockroft-Gault formula to assess the efficacy of the treatment (Toto
1997, Cockroft 1976):

(140 *-* age) x wt (kg) /72 x Scr (mg/dL)

DISCUSSION

Although other formulas to estimate GFR from the serum creatinine
clearance rate are available, they are more cumbersome and have not yet
been recognized as the standards of care. Complete 24-hour urine
collection is also difficult. Several studies have demonstrated close
correlation between the ratio of urine protein to creatinine (urine
protein/creatinine) calculated from random urine collections.

This correlation is near unity with a relatively narrow standard
deviation until daily protein excretion exceeds 3.5 g/dL in diabetic
patients, and even then it distinguishes patients with nephrotic
syndrome from those without (Rodby, 1995). The correlation is most
accurate when testing the first voided morning urine, e.g., a urine
protein/creatinine ratio of 1.0 g/g is equivalent to a 24-h urine
protein excretion rate of 1 g; a ratio of 0.3 g/g would be the
equivalent of 300 mg/24hrs, etc.

For the above reason this panel advocates using the first a.m. voided
urine to determine protein and creatinine levels for screening and
follow-up therapy, unless the proteinuria is above 3.5 g/24 hrs (Rodby
1995; Ginsberg 1983) according to the Cockroft-Gault formula.

**Figure 2. Protein-creatining Ratio to Estimated Protein Excretion**

![](media/image19.png)

Close relation between total daily protein excertion and the total
protein-to-creatinine ratio (mg/mg) determined on a random urine
specimen

(Data from Ginsberg, JM,= Et Al., N Engl J Med 1983. Figure reproduced
from **Up To Date in Medicine**. Rose BD (Ed). Wellesley, MA: V7.1,1999)

[]{.mark}

EVIDENCE

Toto et al., 1997. SR = II, LE = A; Cockroft et al., 1976. SR = II, LE =
B; Rodby et al., 1995. SR = II, LE = B; Ginsberg et al., 1983. SR = II,
LE = B

# Is Urine Protein/Creatinine ratio ≥ 300 mg/gm (0.3 gm/gm) or 24-Hour Urine protein ≥ 300 mg/d?

OBJECTIVE

To help distinguish diabetic from nondiabetic kidney disease.

ANNOTATION

If the 24-hour urine protein excretion is \< 300 mg or the
protein/creatinine ratio is \< 0.3g/g , diabetes is not likely to be the
sole responsible cause of the elevation.

Macroalbuminuria is invariably the stage prior to loss of renal function
and elevation of serum creatinine. In the absence of macroalbuminuria,
other causes of renal failure should be investigated (Nelson 1995).

EVIDENCE

Nelson 1995. SR = N/A, LE = B

# Is Retinopathy Present?

OBJECTIVE

To collect additional evidence confirming the diagnosis of diabetic
nephropathy.

ANNOTATION

If the primary care provider finds retinopathy on an undilated eye exam,
retinopathy is established. Findings such as microaneurysm, flame
hemorrhage, soft or hard exudates, all indicate the presence of
retinopathy. However, if none is seen on undilated exam, a dilated exam
is necessary to confirm the presence of retinopathy.

# Refer to Nephrology

OBJECTIVE

To obtain consultation from a nephrologist regarding the need for
further workup, potentially including renal biopsy.

ANNOTATION

See Annotation E.

# Re-Evaluate for Nondiabetic Causes of Elevated Creatinine

OBJECTIVE

To assure that other potential causes of renal failure are investigated.

ANNOTATION

The workup usually will include renal ultrasound to:

-   Rule out urinary tract outflow obstruction

-   Size the kidneys (small represents long-standing hypertension or
    intrinsic renal disease)

-   Rule out anatomic anomalies (congenital, cysts, mass).

A postvoid residual urine can be helpful in identifying urethral
obstruction (prostate, strictures) or cystopathy as a cause of lower
obstruction. If hematuria is also present, visualization of the bladder
may be warranted. The nephrologist can advise regarding the need for
renal biopsy to rule out glomerulonephritis, collagen vascular disease,
or other etiologies.

# Counsel Patient on Reduced Protein Diet

OBJECTIVE

To advise the patient that lowering his or her protein intake may have a
positive effect on the progression of his or her renal disease.

ANNOTATION

\"In people with type 1 DM and overt diabetic nephropathy, restriction
of dietary protein has been shown to retard the progression toward renal
failure. There is some evidence that this may also be true in type 2 DM.
Therefore, a protein intake of approximately the adult recommended
dietary allowance---0.8 g^-1^/kg body wt^-1^/day^-1^ (\~10 percent of
calories)---is recommended for individuals with evidence of
macroalbuminuria." (ADA 1997)

A number of small studies have demonstrated a slowing of the rate of
progression of type 1 diabetic nephropathy with a low-protein diet (0.6
to 0.7 g/kg/day). However most of these studies were relatively small,
11 to 35 patients (Ciavarella 1987; Evanoff 1989; Walker 1989; Zeller
1991). The largest study of the effect of low-protein diet on all renal
disease, the Modification of Diet in Renal Disease study (Coggins 1994),
did not show this effect to be significant. Only around 50 patients with
diabetes were enrolled and insulin-using patients were specifically
excluded. None of the studies cited above have been long enough to look
at the effect of a low protein diet on progression to ESRD.

Although the value of a low-protein diet has not been adequately
established, this Panel recommends offering it as an option in the
treatment of diabetic nephropathy.

#### Table R3. Clinical Trials of the Effect of Dietary Protein Reduction on the Course of Diabetic Nephropathy in Type 1 DM Patients with Clinical Proteinuria (1)

  --------------- ------------ ------------- --------------- ------------------------
  **Reference**   **No. of     **Treatment   **Protein       **Outcome in Treatment
                  Patients**   Duration**    Restriction**   Group**

  Ciavarella,     16           4.5 months    0.7 g/kg/day    Decreased urinary
  1987                                                       albumin excretion

  Evanoff, 1989   11           24 months     0.6 g/kg/day    Decreased urinary
                                                             protein excretion

  Walker, 1989    19           33 months     0.7 g/kg/day    Decreased rate of GFR
                                                             decline; decreased
                                                             urinary albumin
                                                             excretion

  Zeller, 1991    35           34.7 months   0.6 g/kg/day    Decreased rate of GFR
                                                             decline; decreased
                                                             urinary albumin
                                                             excretion
  --------------- ------------ ------------- --------------- ------------------------

\(1\) Adopted from Nelson, 1995

EVIDENCE

ADA 1997. SR = IIa, LE = C; Ciavarella et al., 1987. SR = IIa, LE =A;
Evanoff et al., 1989. SR = II, LE = B; Walker et al., 1989. SR = II, LE
= B; Zeller et al., 1991. SR = IIa, LE = B

# Does Patient Have \< 1 g/~g\ Cr~ with BP \> 140/85 or \> 1 g/~g\ Cr~ with BP [\>]{.underline} 125/75?

OBJECTIVE

To identify hypertensive patients who may benefit from hypertension
control management.

ANNOTATION

Aggressive treatment of hypertension has been shown to slow the
progression of renal disease.

DISCUSSION

Numerous clinical trials have examined the use of various drugs to slow
the progression of diabetic nephropathy in diabetic persons with
hypertension. The goal of controlling the BP in these patients is to
attain the slowest rate of decline in renal function with the fewest
side effects. However, there may be different optimal blood pressures
to: a) protect the kidneys; and b) prevent cardiovascular events.
Diastolic blood pressures below 80 mmHg have been associated with
increased cardiovascular mortality, but it is not clear whether this is
due to lower diastolic blood pressures being associated with
atherosclerotic disease or to treatment actually worsening mortality.
The Hypertension in Diabetes - Study One trial is attempting to address
this issue---patients are randomized to tight control (BP ≤ 150/≤ 85)
vs. normal (≤ 180/≤ 105) (Merlo 1996; Roca-Cusachs 1993; Hasslacher
1997).

EVIDENCE

Merlo et al., 1996. SR = II, LE = B; Roca-Cusachs 1993. SR = II, LE = C;
Hasslacher 1997. SR = II, LE = C

# Are ACE Inhibitors Contraindicated?

OBJECTIVE

To screen the patient for contraindications to ACE inhibitor use.

ANNOTATION

*Absolute contraindications* are:

-   Pregnancy

-   Hyperkalemia (advanced renal insufficiency or hyporeninemic
    hypoaldosteronism)

-   Known allergy to ACE inhibitors.

*Relative contraindications* are:

-   Known bilateral renal artery stenosis

-   Advanced renal disease.

# Start/Adjust Treatment with ACE Inhibitor. Check Serum Potassium Prior to Starting ACE Inhibitor and Repeat in 2 to 4 Weeks

OBJECTIVE

To ensure that ACE inhibitors do not induce or aggravate hyperkalemia.

ANNOTATION

Use of ACE inhibitors in normotensive diabetic patients with micro- or
macroalbuminuria has been shown to reduce albuminuria and slow
progression of renal disease.

-   Evidence for ACE inhibitors being effective in type 2 DM

> At least one long-term (7 years) randomized (Ravid 1993), placebo
> controlled trial and numerous other shorter term (6 months to 4 years)
> trials in normotensive type 2 DM patients have found a decrease in
> proteinuria with ACE inhibitor treatment (Ravid 1993; Marre 1988;
> Romero 1993; O'Donnell 1993). Evidence for efficacy of ACE inhibitors
> in type 1 DM seems to be conclusive.

-   Frequency of monitoring post therapy

> \"After initiation of therapy with an ACE inhibitor, the efficacy of
> this intervention should be monitored by assessing the
> albumin/creatinine ratio every 3 to 6 months. Because the urine
> albumin-excretion rate would be expected to increase by approximately
> 10 percent to 30 percent per year, stabilization of the
> albumin/creatinine ratio or a reduction in this ratio by up to 50
> percent should be expected.\" It is also recommended to \"check serum
> potassium and creatinine one week after initiation of therapy.\"
> (Bennet 1995)
>
> EVIDENCE
>
> Ravid et al., 1993. SR = IIa, LE = B; Marre et al., 1988. SR = I, LE =
> A; Romero et al., 1993. SR = IIa, LE = A; O'Donnell et al., 1993. SR =
> IIa, LE = A; Bennet, 1995

# Stop ACE Inhibitor Treatment

OBJECTIVE

To ascertain whether side effects have occurred that warrant
discontinuation of the ACE inhibitor.

ANNOTATION

Many patients present with a dry, nonproductive cough from ACE inhibitor
use that resolves when this medication is discontinued. To avoid this
side effect, one of the newer angiotensin II receptor agonists, e.g.,
losarten, may be used. Their specific efficacy in diabetic renal disease
(as opposed to hypertension) is currently being studied. Recurrent
hyperkalemia or a rapid rise in serum creatinine, even on small doses of
an ACE inhibitor, is a second side effect concern. Allergic reactions
such as skin rash may also warrant discontinuation.

# Monitor 24-hour Urine or Spot Urine for Alb/Cr Ratio in 6 Months. Adjust Treatment and Follow-Up as Indicated

OBJECTIVE

To decide whether renal disease is progressing on the current dose of
ACE inhibitor.

ANNOTATION

If albuminuria is progressing or the GFR (as represented by creatinine
clearance) is continuing to decline, a more aggressive treatment should
be considered. The ACE inhibitor could be increased to the maximum
recommended dose. If BP is rising, an additional agent could be added.
Low-protein diet and glycemic control need to be reinforced.

# Monitor for Serum Creatinine and 24-Hour Urine Protein and Creatinine or Spot Urine for Alb/Cr Ratio in One Year 

OBJECTIVE

To decide whether renal disease is progressing on the current regimen
that includes ACE inhibitor, blood pressure control, glycemic control,
and a reduced protein diet.

ANNOTATION

If renal disease is progressing, as evidenced by an increasing serum
creatinine level, a decreasing creatinine clearance rate, or an increase
in proteinuria, the treatment regimen needs to be reevaluated, including
BP and glycemic goals (AMA 1994, 1995, 1997; Bennett 1995; Gall 1991;
Mogensen 1987; Murray 1996; Ordonez & Hiatt 1989; Ravid 1993).

EVIDENCE

American Diabetes Association 1994, 1995, 1997. SR = IIa, LE = C;
Bennett 1995. SR = I, LE = C; Gall et al., 1991. SR = IIa, LE = C;
Mogensen 1987. SR = N/A, LE = B; Murray 1996. SR = I, LE = C; Ordonez &
Hiatt 1989. SR = IIa, LE = C; Ravid et al., 1993. SR = IIa, LE = B

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

# References for Module R

American Diabetes Association. Standards of medical care for patients
with diabetes mellitus. *Diab Care* 1995; 18:8-15

American Diabetes Association. Census development conference on the
diagnosis and management of nephropathy in patients with diabetes
mellitus. *Diab Care* 1994; 17:1357-1361

American Diabetes Association. Position Statement: Diabetic Nephropathy.
*Diab Care* 1997; 20(S1):S24-S27

Bennett PH; Haffner S; Kasiske BL; Keane WF; Mogensen CE; Parving H-H;
Steffes MW; Striker GE. Screening and management of microalbuminuria in
patients with diabetes mellitus. Recommendations to the Scientific
Advisory Board of the National Kidney Foundation from an ad hoc
committee of the Council on Diabetes Mellitus of the National Kidney
Foundation. *Am J Kid Dis* 1995; 25:107-12

Ciavarella A; Di Mizio G; Stefoni S; Borgnino LC; Vannini P. Reduced
albuminuria after dietary protein restriction in insulin- dependent
diabetic patients with clinical nephropathy. *Diab Care* 1987 Jul-Aug;
10(4):407-13

Cockcroft DW; Gault MH. Prediction of creatinine clearance from serum
creatinine. *Nephron* 1976; 16(1):31-41

Coggins CH; Dwyer JT; Greene T; Petot G; Snetselaar LG; Van Lente F.
Serum lipid changes associated with modified protein diets: results from
the feasibility phase of the Modification of Diet in Renal Disease
study. *Am J Kidney Dis* 1994 Apr; 23(4):514-23

Evanoff G; Thompson C; Brown J; Weinman E. Prolonged dietary protein
restriction in diabetic nephropathy. *Arch Intern Med* 1989 May;
149(5):1129-33

[]{.mark}

Gall M; Rossing P; Skott P; Damsbo P; Vaag A; Bech K; Dejgaard A;
Lauritzen M; Lauritzen E. Prevalence of micro- and macroalbuminuria,
arterial hypertension, retinopathy and large vessel disease in European
type II diabetic patients. *Diabetologia* 1991; 34:655-61

Ginsberg JM; Chang BS; Matarese RA; Garella S. Use of single voided
urine samples to estimate quantitative proteinuria. *NEJM* 1983 Dec 22;
309(25):1543-46

Harris, MI; Chapter 2 Classification, Diagnostic Criteria and Screening
for Diabetes. In Harris MI, ed. [Diabetes in America, 2^nd^
edition.]{.underline} Bethesda, Maryland. 1995

Hasslacher C. Hypertension as a risk factor in non-insulin-dependent
diabetes mellitus: how far should blood pressure be reduced? *J Diabetes
Complications* 1997 Mar-Apr; 11(2):90-1

[]{.mark}

Kouri TT; Viikari JS; Mattila KS; Irjala KM. Microalbuminuria.
Invalidity of simple concentration-based screening tests for early
nephropathy due to urinary volumes of diabetic patients. *Diab Care*
1991 Jul; 14(7):591-3

[]{.mark}

Marre M; Chatellier G; Leblanc H; Guyenne T-T; Menard J; Passa P.
Prevention of Diabetic Nephropathy with Enalapril in Normo-tensive
Diabetics with Microalbuminuria. *BMJ* 1988; 297:1092-95

Marre M; Hallab M; Billiard A; Le Jeune JJ; Bled F; Girault A;
Fressinaud P. Small Doses of Ramipril to Reduce Microalbuminuria in
Diabetic Patients with Incipient Nephropathy Independently of Blood
Pressure Changes. *J* *Cardiovasc Pharmacol* 1991; 18(S2):S165-68

Merlo J; Ranstam J; Liedholm H; Hedblad B; Lindberg G; Lindblad U;
Isacsson SO; Melander A; Rastam L. Incidence of myocardial infarction in
elderly men being treated with antihypertensive drugs: population based
cohort study. *BMJ* 1996 Aug 24; 313(7055):457-61

Mogensen CE. Microalbuminuria is a predictor of clinical diabetic
nephropathy. *Kidney Int* 1987; 31:673-89

Murray JE. Microalbuminuria in Type II Diabetes. *Endocrine Practice*
1996; 2:211-14

Ordonez JD; Hiatt RA. Comparison of type II and type I diabetics treated
for end-stage renal disease in a large prepaid health plan population.
*Nephron* 1989; 51:524-29

Physicians Desk Reference. Montvale NJ: Medical Economics Co. 1996

Nelson RG; Pettitt DJ; Knowler WC; Bennett PH. Prediabetic blood
pressure and familial predisposition to renal disease in Pima Indians
with non-insulin-dependent diabetes mellitus. *J Diabetes Complications*
1995 Oct-Dec; 9(4):212-14

O\'Donnell MJ; Rowe BR; Lawson N; Horton A; Gyde OH; Barnett AH.
Comparison of the effects of an angiotensin converting enzyme inhibitor
and a calcium antagonist in hypertensive, macroproteinuric diabetic
patients: a randomized double-blind study. *J Hum Hypertens* 1993 Aug;
7(4):333-39

Ravid M; Savin H; Jutrin I; Bental T; Katz B; Lishner M. Long-term
stabilizing effect of angiotensin converting enzyme inhibition on plasma
creatinine and on proteinuria in normotensive type II diabetic patients.
*Ann Intern Med* 1993; 118:577-81

Roca-Cusachs A. Lowering blood pressure. How far, how fast? *Drugs*
1993; 46 Suppl 2:8-14; discussion 14-15

> Romero R; Salinas I; Lucas A; Abad E; Reverter JL; Johnston S;
> Sanmarti A Renal function changes in microalbuminuric normotensive
> type II diabetic patients treated with angiotensin-converting enzyme
> inhibitors. *Diab Care* 1993 Apr; 16(4):597-600
>
> []{.mark}
>
> Rose BD. (ed). Up To Date in Medicine. Wellesley, MA:(7.1)1999

Schrier RW (Ed.). Renal and Electrolyte Disorders. Little, Brown and
Company. Boston, MA:1976

Toto RD, Kirk KA, Coresh J, Jones C, Appel L, Wright J, Campese V,
Olutade B, Agodoa L, Evaluation of serum creatinine for estimating
gomerular filtration rate in African Americans with hypertensive
nephrosclerosis: results from the African-American study of Kidney
Disease and Hypertension (AASK) Pilot Study.UI-97200412 J Am Soc Nephrol
1997 Feb; 8(2): 279-87

Walker JD; Bending JJ; Dodds RA; Mattock MB; Murrells TJ; Keen H;
Viberti GC. Restriction of Dietary Protein and Progression of Renal
Failture in Diabetic Nephropathy. *Lancet* 1989; 2:1411-15

Zeller K; Whittaker E; Sullivan L; Raskin P; Jacobson HR. Effect of
Restricting Dietary Protein on the Progression of Renal Failure in
Patients with Insulin-Dependent Diabetes Mellitus. *NEJM* 1991;
324:78-84

VHA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF **DIABETES
MELLITUS**

IN THE PRIMARY CARE SETTING

MODULE M - SELF-MANAGEMENT AND EDUCATION

ALGORITHM AND ANNOTATIONS

![](media/image20.png){width="6.509722222222222in"
height="8.429166666666667in"}

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

Module M - Self-Management and Education

# Patient with Newly Diagnosed Diabetes Mellitus?

OBJECTIVE

To ensure that patients with newly diagnosed diabetes mellitus (DM) are
provided with core competency education. For an overview of core
competency (survival skills) information. See appendix M1, Core
Competencies (Survival Skills)

# Provide Information and Education on Basic Concepts, Core Competencies. Document Findings

OBJECTIVE

To ensure that core competencies (survival skills) and other basic
information are understood by patients with diabetes and enable them to
safely self-manage their diabetes.

ANNOTATION

Primary care staff has limited time to provide in-depth education;
however, it is critical to provide:

-   Provide basic concepts and information based on core competencies
    for newly diagnosed patients

-   Identify knowledge/skills deficit expressed in previous algorithms

Core competency education (survival skills) is directed at providing
immediate education that will help ensure the safety of the patient
until in-depth self-management education can be obtained.

The core competencies include:

-   Acute complications (hyperglycemia and hypoglycemia)

-   Medication education

-   Basic diet principles

-   Sick day management

-   When to seek further assistance.

Appendix M1, Core Competencies (Survival Skills) for patient's with
Diabetes, details the core competency content.

The core competencies are not substitutes for an in-depth
self-management education program. Appendices M3, Suggested points of
Contact for Patient Education/Nutrition/Self-management Programs; M4,
Primary Care Staff Office Diabetes Education Resources and Tools; M7,
List of Patient References: Diabetes Resources, lists resources for
diabetes education. Patient education materials from these resources, as
well as other patient education materials, can be made available to the
patient in the office setting to assist the provider in addressing
additional concepts and information not included in core competencies.

Results from the assessment of the patient's learning needs, abilities,
preferences, and readiness to learn, should be documented. Cultural and
religious practices should be included as well as emotional barriers,
desire and motivation to learn, physical and cognitive limitations,
language barriers, and the financial implications of care choices. The
patient's understanding of the newly acquired education should also be
assessed.

# Refer for Comprehensive Self-management and Diet Education 

OBJECTIVE

To provide or refer for comprehensive self-management (SME).and diet
education

ANNOTATION

Diabetes self-management has been deemed necessary by most healthcare
organizations to assist persons with diabetes a) in their day to day
self-management demands; and b) with making informed self-care choices.
This includes the provision of behavioral strategies that establish and
maintain a healthy lifestyle. Since the diabetes clinical state
fluctuates within individuals over their life span, education programs
need to be comprehensive enough to provide clinically relevant knowledge
and skills to facilitate implementation of the changing treatment plans.

Self-management education (SME), including medical nutrition therapy, is
an interactive, collaborative, ongoing process involving people with
diabetes and educators. As opposed to didactic education, SME is skill
based learning. The four-step process comprises:

1.  Assessment of the individual's educational needs

2.  Development of an educational plan to meet the individual's
    identified needs

3.  Educational intervention directed toward helping the person achieve
    identified self-management goals

4.  Evaluation of the individual's level of attainment of the identified
    self-management goals.

Leading experts in diabetes care and education revised the original
National Diabetes Advisory Board (NDAB) Standards (1988). The revised
standards identify the following as essential curricula components for
SME:

-   Diabetes overview

-   Stress and psychological adjustment

-   Family involvement and social support

-   Nutrition

-   Exercise and activity

-   Medication

-   Monitoring and use of results

-   Relationships among nutrition, exercise, medication, and blood
    glucose level

-   Prevention, detection, and treatment of acute complications

-   Prevention, detection, and treatment of chronic complications

-   Foot, skin, and dental care

-   Behavioral strategies, goal setting, and problem solving

-   Benefits, risks, and management options for improving glucose
    control

-   Preconception, pregnancy, and gestational diabetes

-   Use of health care systems and community resources.

Referral for in-depth SME and diet consultation (if separate from the
diabetes self-management program) is recommended for all patients newly
diagnosed with diabetes. Selection of the educational components must be
tailored to patient needs.

The following three ways provide comprehensive education on
self-management and diet:

1.  Refer for in-house comprehensive diet consultation---Medical
    Nutrition Therapy (MNT)---and self-management education program

2.  Refer to a comprehensive SME program in the community. An ADA
    recognized program is recommended, if available (see Appendix M3,
    Suggested Points of Contact for Patient
    Education/Nutrition/Self-management Programs)

3.  Conduct education in your clinical setting in the absence of an
    available comprehensive self-management program. Topics should be
    covered by the most qualified healthcare professionals with special
    knowledge in the topic area. A team approach is highly desirable and
    could include, but is not limited to, referrals to a dietician,
    certified diabetes educator, registered nurse, pharmacist, exercise
    physiologist, physical therapist, social worker, endocrinologist, or
    other specialized physician based on the individual patients' needs.

DISCUSSION

Several retrospective, non-randomized studies, have shown that
comprehensive education results in fewer hospitalizations, better
glycemic control, and imputed economic savings.

The rationale for inclusion of the selected program components was based
on expert opinion and research (Funnel & Haas 1995). Not all the
recommended program components are evidenced based. Because research on
educational interventions is complex, expensive, and time consuming,
little work has been done that addressed the effectiveness of the
program as a whole (Jacobsen 1983; Rubin 1998; Miller 1972; Merrit
1983).

In a randomized, controlled trial, Franz et al., (1995) reported that
patients in the intervention group (n = 94) receiving ongoing MNT (3
visits) from registered dietitians had mean 10.5 percent lower FPG
level; while an intervention group (n = 85) with a single RD
intervention, showed 5.3 percent lower fasting plasma sugar (FPG) level;
and the control group (n = 62) not receiving any medical nutrition
therapy (MNT) from a registered dietitian (RD), showed no improvement in
glycemic control at end of 6 month period.

EVIDENCE

Davidson 1979. Strength of Recommendation (SR) = IIa, Level of Evidence
(LE) = B; Franz 1995. SR = IIa, LE = B; Jacobsen 1983. SR = IIa, LE = B;
Miller 1972. SR = IIa, LE = B; Rubin 1998. SR = IIa, LE = B

# Determine Patient's Extent of Knowledge and Self-management Skill Deficit Based on Treatment Goals 

OBJECTIVE

To determine the education and skills enhancement needed to enable the
patient to self-manage.

ANNOTATION

Assess the patient's knowledge of the diabetes disease process,
treatment goals, management skills, cultural influences, health
beliefs/behavior, attitudes, socioeconomic factors and barriers as each
relates to the patient's ability to self-management and to determine the
extent of his or her education and skills deficit. Choose the questions
that relate to the clinical treatment goals/issues identified pertinent
to the individual patient grouped according to treatment goals:

-   Nutrition and meal planning

-   Goal setting

-   Home monitoring

-   Foot care

-   Exercise

-   Medication

-   Acute complications

-   Psychosocial

-   Preventive screening

-   Treatment adherence

-   Lifestyle.

A panel of certified diabetes educators has compiled a list of initial
questions to assist the provider (see Appendix M5, Questionnaire on
Patient's Knowledge and Compliance). These questions are not to be
interpreted as a validated instrument and may need to be adjusted to fit
the patient's level of education and/or ability to comprehend what he or
she is being asked.

Appendix M6, Patient Self-management and Knowledge Needs Assessment,
includes the desired patient response to the questions in appendix M5,
and suggested actions to take when the patient is unable to demonstrate
knowledge/skills.

# Does Patient Need Referral for Further Education or Intervention?

OBJECTIVE

To identify patients who are at high risk for diabetes complications or
need further educational intervention.

ANNOTATION

Because primary care appointments are frequently too short to provide
adequate time to address background and educational issues, a referral
or separate visit(s) to address the patient\'s needs may be required.
This may involve sending the patient to the comprehensive
self-management program, possibly for a second time. However it may be
necessary to send the patient to another clinician/specialist for
individual visit(s) to evaluate and address, an often complex
combination of educational issues, treatment issues, coordination of
care issues, psychosocial issues or financial issues. High risk patients
may benefit from these types of referrals. Decisions for referral are
based on level of risk and extent of educational deficits.

Examples of conditions that may warrant risk-focused intervention are:

-   Elevated HbA~1~c (3 percent above the upper limit of normal or \>
    9.5 percent)

-   Uncontrolled hypertension

-   Serum creatinine level \> 2 mg/dL

-   High risk feet

-   Pregnancy; or planned pregnancy; or woman of child bearing age

-   Poor eyesight

-   Severe psycho-social or economic barriers

-   Advanced age

-   Intensive insulin therapy

-   Recurrent hypoglycemia or hypoglycemia unawareness

-   Recent hospitalization for diabetic ketoacidosis (DKA) or severe
    hyperglycemia.

The need for risk-focused interventions may also have been identified
through algorithms G, F, L, H, and E.

Deficiencies in any of the critical areas from the history section of
Algorithm D Core may indicate patient knowledge needs in multiple areas
and should trigger referral for comprehensive diabetes SME.

# Refer for Risk-Focused Intervention or to Case Manager or to Appropriate Specialist

OBJECTIVE

To determine which referrals are appropriate based on patient\'s needs
and availability of providers, programs, and benefit coverage.

ANNOTATION

After explaining the basic concepts, if the primary care team determines
that the patient does not yet understand concepts or would benefit from
a more in-depth, risk-focused education or intervention, a consultation
should be requested.

In some cases, more than an educational intervention is required.
Patients at high risk may have needs beyond educational deficits and
referral for focused attention from other services is indicated.
Possible referrals could include, but are not limited to:

-   Dietitian

-   Certified diabetes educator or comprehensive Diabetes
    Self-management Education Program

-   Case Manager

-   Registered nurse

-   Pharmacist

-   Psychologist

-   Exercise physiologist

-   Physical therapist

-   Social worker

-   Endocrinologist.

... or other specialist based on the individual patient's needs, e.g.,
family counseling or social work. Case managers are a valuable resource
for providing ongoing, detailed coordination of care for high-risk
patients.

DISCUSSION

Aubert et al. (1999) reported that in a health maintenance organization
(HMO), patients who were case managed and prospectively studied, had
improved glycemic control, increased quantitative protein and
microalbuminuria testing and follow-up testing, when compared
retrospectively to those who were not case managed.

Franz (1995) reported that patients with type 2 diabetes who were
randomly selected to receive (Medical Nutrition Therapy) from dietitians
were more likely to have lowered HbA~1~c than those who continued to
receive care from physicians alone during the 6-month trial.

EVIDENCE

Aubert et al., 1998. SR = IIa, LE = B; Franz 1995 SR = IIb, LE = C;
Sikka et al., 1999. SR = IIb, LE = B

# Reassess and Follow-Up as Indicated

OBJECTIVE

Identify the frequency of patient appointments needed to evaluate
educational effectiveness or reinforce education/self-management skills.

ANNOTATION

When knowledge deficits still exist or a large number of lifestyle
changes are necessary, frequent follow-up may be indicated. Panel
experts recommend that recently learned diabetes skills or information
be re-evaluated no longer than 3 months after initial instruction.

Single behavioral goals should be identified and prioritized to increase
the likelihood of the patient adopting lifestyle changes necessary to
achieve treatment goals.

DISCUSSION

Definitive evidence is not available to support specific frequencies of
follow-up. Therefore, frequency of re-assessment should be
individualized based patient's and provider's perception of need. Panel
experts recommend that re-assessment of recently learned diabetes skills
or information be re-evaluated within 3 months of initial instruction.
Garcia (1996) documented the benefit of interactive and ongoing
education and the need to provide individualized follow-up. Glasgow
(1992) compared the immediate and delayed intervention and concluded
that both could achieve positive results. Frequency of appointments has
been reported from weekly to annually (Pascale 1995; Conget, 1995). The
importance of individualization and tailoring sessions to participants
needs has been amply documented (Schlundt 1994; Ellison 1998; Travis
1997; Monk 1995; Conget 1995; Arseneau 1994).

# Does the Patient Want More Information? 

OBJECTIVE

To address patient's desire (motivation) for additional information.

ANNOTATION

Patients often hear of developments, or may have specific questions,
about newer treatment modalities. They may also decide they want to
improve their glycemic control or their life style.

# Provide Materials or Patient Reference List or Refer as Needed

OBJECTIVE

# 

To provide additional information in response to patients' questions
about new treatments or advanced self-management skills that have been
communicated from other persons with diabetes or the media.

ANNOTATION

When patients request additional information and it may not be essential
for the caregiver to intervene professionally or refer to a specialist,
Appendix M7, List of Patient References: Diabetes Resources, provides
the patient with adequate references.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

Appendix M1. Core Competencies (Survival Skills) for Patients with
Diabetes

The following core competencies are not substitutes for self-management
education or medical nutrition therapy.

It is preferable for patients to participate in a comprehensive
interdisciplinary diabetes self-management education program. If such a
program is not available, if patient is unwilling to attend, or if newly
diagnosed and awaiting enrollment in such a program, core competency
(survival skills) education should be given. Such education should cover
at least the following topics:

-   Hyperglycemia

-   Hypoglycemia (if applicable)

-   Medication education (including insulin administration if
    applicable)

-   Basic dietary guidelines

-   Sick day management

-   When to seek further treatment and/or medical advice.

HYPERGLYCEMIA

• *Definition*: Blood glucose ≥ 250 mg/dL

• *Causes:* Forgetting to take diabetes medication

Overeating

Infection/Illness

Stress

Not exercising

Not taking enough diabetes medication

• *Symptoms:* Fatigue

Polydipsia

Polyuria, especially nocturnal

Blurry vision

• *Intervention/Treatment:*

Drink plenty of non-caloric fluids

> Increase self-monitoring of blood glucose (SMBG) before meals and
> bedtime while awake until blood glucose is ≤ 200. If DM is type 1,
> urine ketones should also be tested

Continue to take prescribed diabetes medication

> Follow meal plan.

HYPOGLYCEMIA

• *Definition:* Blood glucose \< 70 mg/dL

• *Causes:* Delaying meals

Not eating enough food

Too much diabetes medication

Too much exercise

• *Symptoms:* Weakness

Rapid heart beat

Sweating

Shakiness

Light-headedness or confusion

######## Intervention/Treatment*: If patient unconscious, spouse or friend should call 911*

-   If conscious, treat immediately by eating a food or glucose
    replacement with 15 to 20 g of fast-acting carbohydrates (CHO) (see
    Appendix M2)

-   If on acarbose, treat with a glucose product (tabs or gel equal to
    15-20 g CHO)

-   Check blood glucose in 15 minutes. If less than 70 mg/dl or symptoms
    have not subsided, take an additional 15g CHO

-   Eat a meal or combination CHO/protein snack within 30 minutes

-   If blood glucose is less than 70 and does not increase after eating,
    seek further medical help.

Medication Education (if appropriate)

Education regarding diabetes medications should include:

-   Name of medication(s)

-   Action & duration of medication(s)

-   Times & mode of administration

-   Possible side effects

-   Drug/food interactions.

Education for patients receiving insulin should also include the
following:

-   Preparation of equipment

-   Filling of the syringe

-   Administration

-   Insulin action(s), e.g., onset(s), peak(s), and duration(s)

-   Insulin storage

-   Needle/syringe disposal

-   Rotation within selected anatomical sites

-   Demonstration with return demonstration by the patient.

BASIC DIET GUIDELINES

Meal plans can be initiated with use of the "FIRST STEP in Diabetes Meal
Planning." This basic, self-contained nutrition pamphlet can be reviewed
and provided to clients to use until an individualized meal plan can be
developed.

General principles to be reviewed are:

-   Eat at regular times---distribute CHO food intake throughout the day

-   Define CHO, protein, and fat

-   Describe which foods affect blood sugar the most (e.g., CHO)

-   Emphasize importance of eating a variety of foods, increasing fiber,
    and a hypocaloric diet---if overweight, e.g., decreasing fat intake
    and controlling portion sizes.

SICK DAY MANAGEMENT

The main sick day management rules are:

-   Take diabetes medication

-   Self-monitor blood glucose more frequently

-   Test urine ketones if DM type 1

-   Eat the usual amount of CHO divided into smaller meals and snacks if
    necessary---if blood glucose is [\>]{.underline} 250 mg/dL, the
    usual CHO may be unnecessary

-   Drink fluids frequently, 8 oz per hour while awake

-   Refer to example of sick day guide (see Appendix 2).

When to seek further medical ASSISTANCE

-   Blood glucose \> 250 or double the range set with the primary care
    provider

-   If blood sugar is less than 70 and does not get better when you eat
    food call the doctor

-   Urine test revealing moderate to high ketones

-   Fever of 101 degrees Fahrenheit or greater

-   Nausea and vomiting, especially if no food or fluid intake for more
    than 5 hours

-   Symptoms of shakiness or nervous feeling, lightheadedness, sweating,
    rapid heart rate or confusion that does not improve after eating

-   Any of the following problems on the feet: burns, splinters, stubbed
    toe, foot trauma, blister, swelling, black or blue discoloration,
    bleeding, or oozing of fluid.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**Appendix M2**. **Food for Sick Days and Hypoglycemia**

HYPOGLYCEMIA TREATMENT

Items in this table can be used for immediate treatment of
hypoglycemia/low blood sugar. The items in the fruit and other
carbohydrate list will relieve the symptoms of hypoglycemia the fastest.
In addition to the food items listed, commercial glucose products
containing 15 to 20 g carbohydrates (CHO) may be used (glucose tablets
or gels).

  --------------------- ---------------------- ------------- --------------
  **Fruit List**        **Other                **Milk**      **Starches**
                        Carbohydrates**                      

  1/2 cup orange juice  4 oz regular cola (1/2 1 cup         3 Graham
                        cup)                   **skim** milk crackers

  1/2 cup grapefruit,   6 oz regular ginger    1/2 cup       8 animal
  pineapple, or apple   ale                    pudding       crackers
  juice                                                      

  1/3 cup cranberry,    1 tablespoon honey ,                 6 Saltine
  grape or prune juice  brown sugar, or corn                 crackers
                        syrup                                

                        1/2 cup sherbet                      
  --------------------- ---------------------- ------------- --------------

FOODS FOR SICK DAYS

1.  Take your pills or insulin. You may need to take more insulin than
    normal.

2.  Check your blood sugar every 4 hours. If it above 250 mg, also check
    the urine for ketones.

3.  If you are sick and your blood sugar is above 250 mg and urine
    ketones are positive on 2 consecutive checks, call your doctor or
    clinic nurse.

4.  If blood sugar is consistently very high after 2 to 3 checks (above
    300 mg) call your doctor even if the urine does not show ketones.

5.  Drink fluids; at least 1/2 - 1 cup every hour.

6.  Eat frequent small meals of whatever foods you can tolerate and
    replace carbohydrate containing foods that would have normally been
    in your daily plan.

> 1 Starch = 15g CHO
>
> 1 Fruit = 15g CHO
>
> 1 Milk = 12g CHO

If the person with diabetes is nauseated and can not keep down solid
food, replace food items on meal plan with other items from same food
group if possible, e.g., replace a slice of bread with saltine crackers,
or cream soup, or vegetables with tomato juice.

Each portion on the following table contains 15g of carbohydrate:

+----------------------------+----------+--------------------+--------+
| # Soli                     |          | Beverages          |        |
| d Foods Containing 15g CHO |          | Containing 15g CHO |        |
+----------------------------+----------+--------------------+--------+
| ######### **Food**         | **       | **Food**           | **Am   |
|                            | Amount** |                    | ount** |
+----------------------------+----------+--------------------+--------+
| **Milk List**              |          |                    |        |
+----------------------------+----------+--------------------+--------+
| > Yogurt (artificially     | 1 cup    | Skim or low fat    | 1 1/4  |
| > sweetened)               |          | milk               | cup    |
+----------------------------+----------+--------------------+--------+
| Yogurt (with fruit)        | 1/3 cup  |                    |        |
+----------------------------+----------+--------------------+--------+
| > Vanilla pudding          | 1/4 cup  |                    |        |
+----------------------------+----------+--------------------+--------+
| > Ice cream (no sugar      | 1/2 cup  |                    |        |
| > added)                   |          |                    |        |
+----------------------------+----------+--------------------+--------+
| > Ice milk (no sugar       | 1/2 cup  |                    |        |
| > added)                   |          |                    |        |
+----------------------------+----------+--------------------+--------+
| **Starch List**            |          |                    |        |
+----------------------------+----------+--------------------+--------+
| > Cooked cereal            | 1/2 cup  | Chicken noodle     | 1 cup  |
|                            |          | soup               |        |
+----------------------------+----------+--------------------+--------+
| > Toast (bread)            | 1 slice  | Cream soup         | 1 cup  |
+----------------------------+----------+--------------------+--------+
| > Graham crackers (2 ½     | 3        |                    |        |
| > inch)                    |          |                    |        |
+----------------------------+----------+--------------------+--------+
| > Animal crackers          | 8        |                    |        |
+----------------------------+----------+--------------------+--------+
| > Saltine crackers (2      | 6        |                    |        |
| > inch)                    |          |                    |        |
+----------------------------+----------+--------------------+--------+

+----------------------------+----------+--------------------+--------+
| **Fruit List**             |          |                    |        |
+----------------------------+----------+--------------------+--------+
|                            |          | Grapefruit,        | 1/2    |
|                            |          | orange, or         | cup    |
|                            |          | pineapple juice    |        |
+----------------------------+----------+--------------------+--------+
| > 2 T raisins              |          | Grape or cranberry | 1/3    |
|                            |          | juice              | cup    |
+----------------------------+----------+--------------------+--------+
| **Vegetable List**         |          |                    |        |
+----------------------------+----------+--------------------+--------+
|                            |          | Tomato juice       | 1 1/2  |
|                            |          |                    | cup    |
+----------------------------+----------+--------------------+--------+
| **Other**                  |          |                    |        |
+----------------------------+----------+--------------------+--------+
| > Regular gelatin          | 1/3 cup  | Ginger ale,        | 6 oz   |
|                            |          | regular            |        |
+----------------------------+----------+--------------------+--------+
| > Twin popsicle            | 3/4      | Cola, regular      | 4 oz   |
|                            | popsicle |                    |        |
+----------------------------+----------+--------------------+--------+
| > Sherbet                  | 1/4 cup  | Corn syrup         | 1 T    |
+----------------------------+----------+--------------------+--------+
| > Honey                    | 1 T      |                    |        |
+----------------------------+----------+--------------------+--------+
| > Brown Sugar              | 1 T      |                    |        |
+----------------------------+----------+--------------------+--------+

# References for Appendix M2

American Diabetes Association, American Dietetics Association: The First
Step in Diabetes Meal Planning, 1995

Bectron Dickinson Consumer Products: Getting Started-Controlling Low
Blood Sugar Reactions, n/d.

Holler H; Pastors J. Diabetes Medical Nutrition Therapy. American
Dietetic Association, American Diabetes Association, 1997

Mitchell-Funnel, M. A Core Curriculum for Diabetes Education.
"Hypoglycemia" Chapter 14, pp. 441-473; "Management of Illness and
Surgery" Chapter 15 pp. 477-499; "Special Topics in Meal Planning:
Chapter 10 pp. 83-92. Third edition. American Association of Diabetes
Educators, 1998.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

#### Appendix M3. Suggested Points of Contact for Patient Education/Nutrition/Self-Management Programs

National or Regional affiliates of The American Diabetes Association
maintain lists of local programs that have received recognition that
they meet the national Standards for Diabetes Self-Management Education
Program. The national office is (1-800-diabetes \[342-2383\]). The web
site address is [http://www.diabetes.org]{.underline}

The national office of The Center for Disease Control (CDC) can also
provide the name of each State Diabetes Control Program and identify any
programs endorsed through the state programs. State certification is
usually based on the national standards for Diabetes Self-Management
Education Programs. The telephone number for the CDC is
(1-877-232-3422); the web site address is
[http://www.cdc.gov/diabetes/]{.underline}

Lists of registered dietitians that provide nutrition counseling are
available from The American Dietetic Association by calling
1-800-877-1600 or checking the web site:
[http://www.eatright.org/journal/]{.underline}

The American Dietetic Association\'s Nationwide Nutrition Network is a
national referral service that links consumers, physicians, food
manufacturers, distributors or restaurant owners or managers with
registered dietitians. All participants in The American Dietetic
Association\'s Nationwide Nutrition Network (dietitian referral service)
are registered dietitians---professionals who provide reliable,
objective nutrition information, separate facts from fads and translate
the latest scientific findings into easy-to-understand nutrition
information. The web site address is http://www.eatright.org/find.html
or go to the http://www.eatright.org and select *Find a* *Dietitian*
from the bottom menu.

Lists of certified diabetes educators (CDE) are available. These
professionals have passed the certification examination administered by
the National Certification Board for Diabetes Education (NCBDE) (Klein
1984). A guide of CDEs is available by calling 1-800-338-DMED.

# References for Appendix M3

Klein R; Klein BEK; Moss SE; Davis MD; et al: The Wisconsin Study of
Diabetic Retinopathy II. Prevalence and risk of diabetic retinopathy
when age at diagnosis is less than 30 years. *Arch Ophthalmol* 1984a;
102:520-26

Klein R; Klein BEK; Moss SE; Davis MD; et al: The Wisconsin Study of
Diabetic Retinopathy III. Prevalence and risk of diabetic retinopathy
when age at diagnosis is 30 or more years. *Arch Ophthalmol* 1984b; 102:
527-32.

**MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING**

# 

#### Appendix M4. Primary Care Staff Office Diabetes Education Resources and Tools

SUGGESTED REFERENCES FOR OFFICE

Life with Diabetes. A Series of Teaching Outlines, The American Diabetes
Association, University of Michigan. Diabetes Research and Training
Center. 1997 (Has teaching plans)

Ordering information: Web site:
http://merchant.diabetes.org[/adabooks]{.underline}

Take Charge of your Diabetes. Second edition. Can be downloaded from CDC
web site: http://www.cdc.gov/nccdphp/ddt/ddthome

Managing your Diabetes: A Comprehensive Guide for Patients and
Professionals

Phone number 1-800-545-5979 or

Web site: [www.lilly.com/diabetes]{.underline}

Series of three booklets:

I have Diabetes: How Much Should I eat

I have Diabetes: What Should I Eat

I have Diabetes: When Should I Eat

These booklets can be obtained free from National Diabetes Clearing
House (301) 654-3327 or at
h[ttp://www.ndic@info.niddk.nih.gov]{.underline}

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

#### Appendix M5. Questionnaire on Patient's Knowledge and Compliance

  --------------- -------------------------------------------------- -------------
  **Treatment     **Question** (a)                                   **Response
  Goals**                                                            Accurate?**

  Nutrition &     What times of the day do you eat your meals and    
  Meal Planning   snacks? What is the relationship of your meals to  
                  when you take your medication?                     

                  When should you eat in relationship to the time    
                  when you take insulin/medication?                  

                  Which food affects your blood sugar the            
                  most---chicken breast, salad, or a potato?         

  Goal Setting    Do you remember your target goals? (HbA~1~c, LDL,  
                  weight, exercise, blood sugar, blood pressure)     

                  What are your target goals? (HbA~1~c, LDL, weight, 
                  exercise, blood sugar, blood pressure)             

  Home Monitoring When do you test your blood sugar?                 

                  What are your blood sugar results and how do you   
                  use them to manage your diabetes?                  

  Foot Care       How often do you look at your feet?                

                  When would you contact a health care provider when 
                  you have a foot problem?                           

                  What are the symptoms of food disease and when     
                  would you contact your provider?                   

  Exercise        What effect does exercise have on your blood       
                  sugar?                                             

  Medication      What diabetes medicine do you take and how often?  

                  Do you take your diabetic medication when you are  
                  sick and unable to keep food down?                 

  Acute           Do you know what to do when your sugars are too    
  Complications   low, too high, and when to call your provider?     

  Psychosocial    Are there any problems in your life that make it   
                  difficult for you to take care of your diabetes?   

                  Are you overwhelmed by your diabetes?              

                  Do you worry about developing complications of     
                  diabetes?                                          

  Preventive      Do you know why you have to have periodic eye      
  Screening       examinations?                                      

                  Have you scheduled your annual eye and foot        
                  examinations?                                      

  Treatment       Is there anything that has been recommended that   
  Adherence       you do for your diabetes that you think you will   
                  have difficulty with, or will be unable to do?     

                  What part of diabetes treatment do you have        
                  difficulty with?                                   

  Lifestyle       How do alcohol and cigarettes affect your          
                  diabetes?                                          

                  Do you want to get pregnant---either now or in the 
                  near future?                                       

                  If you are sexually active, what contraception     
                  methods are you using?                             

                  Have there been any major changes in your life     
                  (family crisis, job loss)?                         
  --------------- -------------------------------------------------- -------------

# See Appendix 6 for desired responses and proposed actions to be taken.

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

**Appendix M6. Questionnaire on Patient's Knowledge and Compliance**

+---------+-------------------+-------------------+-------------------+
| **Tr    | **Questions to    | **Patient         | **Suggested       |
| eatment | Ask\              | Response**        | Actions**         |
| Plan &  | **                |                   |                   |
| Goals** |                   |                   | **to be Taken**   |
+---------+-------------------+-------------------+-------------------+
| **Nu    | 1.  What times of | If patient        | Take complete     |
| trition |     the day do    | indicates         | nutrition history |
| & Meal  |     you eat your  | irregular eating  | to determine      |
| Pla     |     meals and     | schedule then     | extent to which   |
| nning** |     snacks and    | nutrition/diet    | self-management   |
|         |     what is the   | behavior is       | skills have been  |
|         |     relationship  | problematic.      | incorporated into |
|         |     of taking     |                   | lifestyle,        |
|         |     your          | If patient unable | identify          |
|         |     medication to | to explain        | barriers, and     |
|         |     your meals?   | relationship      | create self       |
|         |                   | between time of   | management        |
|         | 2\. When should   | eating and        | plan---or refer   |
|         | you eat in        | medication, then  | for nutrition     |
|         | relationship to   | consider it a     | counseling or     |
|         | the time when you | nutrition         | comprehensive     |
|         | take insulin?     | knowledge deficit | diabetes self     |
|         |                   |                   | management        |
|         | 3\. Which food    | If patient can't  | program.          |
|         | affects you blood | answer that       |                   |
|         | sugar the most,   | potatoes will     | Refer to          |
|         | chicken breast,   | have most effect, | dietitian or take |
|         | salad, or a       | then consider it  | nutrition         |
|         | potato?           | a knowledge       | history,          |
|         |                   | deficit about     | determine calorie |
|         |                   | nutrition.        | needs, identify   |
|         |                   |                   | normal eating     |
|         |                   |                   | habits, identify  |
|         |                   |                   | foods and meal    |
|         |                   |                   | planning          |
|         |                   |                   | principles that   |
|         |                   |                   | will match        |
|         |                   |                   | patient's needs,  |
|         |                   |                   | identify goals    |
|         |                   |                   | for diet changes  |
|         |                   |                   | to be made, and   |
|         |                   |                   | establish         |
|         |                   |                   | follow-up         |
|         |                   |                   | appointment.      |
+---------+-------------------+-------------------+-------------------+
| # Goal  | 1.  Do you        | If patient can    | Explain target    |
| Setting |     remember your | not verbalize     | goals and assess  |
|         |     target goals  | target goals      | if patient knows  |
|         |     (HbA~1~c,     | consider it a     | what behaviors    |
|         |     LDL, weight,  | knowledge         | are linked to     |
|         |     exercise,     | deficit.          | those goals. And  |
|         |     blood sugar,  |                   | explore to see if |
|         |     BP)?          |                   | other knowledge   |
|         |                   |                   | deficits exist    |
|         | *or*              |                   |                   |
|         |                   |                   |                   |
|         | 2.  What are your |                   |                   |
|         |     target goals  |                   |                   |
|         |     (HbA~1~c,     |                   |                   |
|         |     LDL, weight,  |                   |                   |
|         |     exercise,     |                   |                   |
|         |     blood sugar,  |                   |                   |
|         |     BP)?          |                   |                   |
+---------+-------------------+-------------------+-------------------+
| **Home  | 1.  When do you   | Consider it a     | Educate the       |
| Monit   |     test your     | knowledge deficit | patient on the    |
| oring** |     blood sugar?  | if patient is     | importance of     |
|         |                   | unable to         | SMBG to their     |
|         | 2\. What are your | verbalize that    | diabetes          |
|         | blood sugar       | self-monitoring   | self-management   |
|         | results and how   | of blood glucose  | and recommend     |
|         | do you use them   | (SMBG) schedules  | schedule for      |
|         | to manage your    | is based on the   | SMBG. Timing of   |
|         | diabetes?         | individual's      | glucose           |
|         |                   | needs, desires    | monitoring is     |
|         |                   | and use of the    | variable          |
|         |                   | results, e.g.,    | depending on the  |
|         |                   | more frequent     | medication and    |
|         |                   | monitoring during | glucose goals.    |
|         |                   | insulin           |                   |
|         |                   | adjustment versus | Recommend         |
|         |                   | periodic          | referral to CDE   |
|         |                   | postprandial      | on SMBG when      |
|         |                   | glucose on        | individual is     |
|         |                   | individual with   | deficient in      |
|         |                   | type 2 diabetes.  | testing skills    |
|         |                   |                   | and/or utilizing  |
|         |                   | If patient is     | results of SMBG   |
|         |                   | unable to         | to manage         |
|         |                   | verbalize that    | diabetes.         |
|         |                   | SMBG may be used  |                   |
|         |                   | for: identifying  | Recommend         |
|         |                   | and treating low  | referral to CDE   |
|         |                   | blood sugar;      | if individual     |
|         |                   | making decisions  | having frequent   |
|         |                   | about food        | low/high blood    |
|         |                   | choices,          | sugar results.    |
|         |                   | medication        |                   |
|         |                   | adjustment and    | Base treatment    |
|         |                   | exercise;         | recommendations   |
|         |                   | determining       | (meal             |
|         |                   | effect of certain | plan/exe          |
|         |                   | foods/portions on | rcise/medication) |
|         |                   | blood sugars;     | on individual's   |
|         |                   | pattern           | SMBG results.     |
|         |                   | management;       |                   |
|         |                   | managing illness; |                   |
|         |                   | and managing      |                   |
|         |                   | hypoglycemia      |                   |
|         |                   | unawareness       |                   |
|         |                   | consider it a     |                   |
|         |                   | knowledge deficit |                   |
|         |                   |                   |                   |
|         |                   | If SMBG results   |                   |
|         |                   | are not within    |                   |
|         |                   | goals consider    |                   |
|         |                   | that it could be  |                   |
|         |                   | a knowledge       |                   |
|         |                   | deficit or        |                   |
|         |                   | behavior issue.   |                   |
+---------+-------------------+-------------------+-------------------+

\(a\) See Appendix 6 for desired responses and proposed actions to be
taken.

#### Appendix M6. Patient Self-management and Knowledge Needs Assessment (continued)

+---------+-------------------+-------------------+-------------------+
| **Tr    | > **Questions to  | > **Patient       | > **Suggested     |
| eatment | > Ask\            | > Response**      | > Actions**       |
| Plan &  | > **              |                   | >                 |
| Goals** |                   |                   | > **to be Taken** |
+---------+-------------------+-------------------+-------------------+
| >       | > 1\. How often   | > Consider it a   | > Instruct in     |
|  **Foot | > do you look at  | > knowledge       | > importance of   |
| >       | > your feet?      | > deficit if      | > foot care and   |
|  care** |                   | > patient can not | > shoe selection. |
|         | 2.  When do you   | > verbalize       | > Then ask        |
|         |     contact a     | > appropriate     | > several more    |
|         |     health care   | > behavior:       | > unrelated       |
|         |     provider      | >                 | > questions to    |
|         |     about a foot  | > Examine feet    | > determine if    |
|         |     problem?      | > daily including | > general         |
|         |                   | > between the     | > knowledge of    |
|         | > or              | > toes;           | > diabetes        |
|         | >                 | >                 | > self-management |
|         | > 3\. What are    | > Washing feet    | > is missing.     |
|         | > the symptoms of | > daily; and      | >                 |
|         | > foot disease    | >                 | > If more areas   |
|         | > and when would  | > Proper          | > are deficient   |
|         | > you contact     | > selection of    | > begin           |
|         | > your provider?  | > footwear        | > scheduling a    |
|         |                   | >                 | > series of       |
|         |                   | > ... then        | > appointments    |
|         |                   | > determine if    | > for education   |
|         |                   | > knowledge or    | > and provide     |
|         |                   | > behavior is the | > written         |
|         |                   | > issue.          | > material to     |
|         |                   | >                 | > review prior to |
|         |                   | > Consider it a   | > discussion (see |
|         |                   | > knowledge       | > Appendix 3) or  |
|         |                   | > deficit if      | > refer for an    |
|         |                   | > patient does    | > educational     |
|         |                   | > not indicate    | > needs           |
|         |                   | > that any time   | > assessment from |
|         |                   | > there is heat,  | > CDE,            |
|         |                   | > redness,        | > podiatrist, or  |
|         |                   | > swelling, or    | > diabetes        |
|         |                   | > infection, the  | > program         |
|         |                   | > provider should | > manager.        |
|         |                   | > be contacted.   |                   |
|         |                   | >                 |                   |
|         |                   | > Consider it a   |                   |
|         |                   | > knowledge       |                   |
|         |                   | > deficit if      |                   |
|         |                   | > patient can not |                   |
|         |                   | > verbalize signs |                   |
|         |                   | > and symptoms of |                   |
|         |                   | > foot disease,   |                   |
|         |                   | > and to contact  |                   |
|         |                   | > the provider if |                   |
|         |                   | > there are       |                   |
|         |                   | > burns,          |                   |
|         |                   | > splinters,      |                   |
|         |                   | > blisters,       |                   |
|         |                   | > stubbed toe,    |                   |
|         |                   | > trauma, black & |                   |
|         |                   | > blue            |                   |
|         |                   | > discoloration,  |                   |
|         |                   | > bleeding or     |                   |
|         |                   | > oozing of       |                   |
|         |                   | > fluid, heat,    |                   |
|         |                   | > redness,        |                   |
|         |                   | > swelling, or    |                   |
|         |                   | > infection,      |                   |
+---------+-------------------+-------------------+-------------------+
| # E     | > 1\. What effect | > If patient      | > Instruct on     |
| xercise | > does exercise   | > cannot          | > planning for    |
|         | > have on your    | > verbalize that  | > exercise,       |
|         | > blood sugar?    | > exercise in     | > including       |
|         |                   | > most situations | > adjustments of  |
|         |                   | > will lower      | > medication and  |
|         |                   | > blood sugars,   | > food, and       |
|         |                   | > consider it a   | >                 |
|         |                   | > knowledge       | contraindications |
|         |                   | > deficit         | > for exercise.   |
|         |                   |                   | >                 |
|         |                   |                   | > Referral        |
|         |                   |                   | > indicated if    |
|         |                   |                   | > other knowledge |
|         |                   |                   | > deficits exist. |
+---------+-------------------+-------------------+-------------------+

+---------+-------------------+-------------------+-------------------+
| **Tr    | > **Questions to  | > **Patient       | > **Suggested     |
| eatment | > Ask\            | > Response**      | > Actions**       |
| Plan &  | > **              |                   | >                 |
| Goals** |                   |                   | > **to be Taken** |
+---------+-------------------+-------------------+-------------------+
| # Medi  | > 1\. What        | > Consider it a   | > Educate patient |
| cations | > diabetes        | > knowledge       | > on:             |
|         | > medicine do you | > deficit if the  | >                 |
|         | > take and how    | > patient does    | > a\) Importance  |
|         | > often?          | > not recall what | > of knowing the  |
|         | >                 | > medication(s)   | > medications for |
|         | > 2\. Do you take | > he/she is       | > the treatment   |
|         | > your diabetes   | > taking, it is   | > of diabetes;    |
|         | > medication when | > unlikely that   | >                 |
|         | > you are sick    | > he or she knows | > b\) Its         |
|         | > and unable to   | > its potential   | > potential side  |
|         | > keep food down? | > side effects    | > effects; and    |
|         |                   | > and how to take | >                 |
|         |                   | > it              | > c\) When they   |
|         |                   | > appropriately   | > should be taken |
|         |                   | > (e.g., acarbose | > to obtain the   |
|         |                   | > needs to be     | > best results.   |
|         |                   | > taken at the    | >                 |
|         |                   | > time of the     | > Sick-day        |
|         |                   | > meal).          | > guidelines      |
|         |                   | >                 | > keeping in mind |
|         |                   | > Consider it a   | > the particular  |
|         |                   | > knowledge       | > agent they are  |
|         |                   | > deficit if      | > on (see         |
|         |                   | > patient is      | > Appendix 2).    |
|         |                   | > unable to       | >                 |
|         |                   | > identify what   | > Address         |
|         |                   | > to do in this   | > barriers        |
|         |                   | > situation (see  | > limiting        |
|         |                   | > Appendix 2 for  | > treatment       |
|         |                   | > desired         | > adherence       |
|         |                   | > responses).     | >                 |
|         |                   | >                 | > Deficiency in   |
|         |                   | > If patient      | > either one of   |
|         |                   | > verbalizes what | > this questions  |
|         |                   | > is supposed to  | > in addition to  |
|         |                   | > happen, but     | > another major   |
|         |                   | > indicates       | > category or of  |
|         |                   | > inability to    | > this is not the |
|         |                   | > follow regimen, | > first time the  |
|         |                   | > then consider   | > patient has had |
|         |                   | > it a knowledge  | > difficulty with |
|         |                   | > deficit.        | > this category   |
|         |                   | >                 | > should trigger  |
|         |                   | > If patient is   | > a referral for  |
|         |                   | > unable to       | > either          |
|         |                   | > verbalize the   | > comprehensive   |
|         |                   | > importance of   | > diabetes self   |
|         |                   | > frequent home   | > management      |
|         |                   | > monitoring and  | > education       |
|         |                   | > to increase     | > program or      |
|         |                   | > medication      | > individual      |
|         |                   | > dosage if BS    | > appointment     |
|         |                   | > (if applicable) | > with            |
|         |                   | > is high and     | > appropriate     |
|         |                   | > that they       | > prov            |
|         |                   | > should call     | ider\--dietitian, |
|         |                   | > provider if     | > CDE,            |
|         |                   | > food or fluids  | > pharmacist, or  |
|         |                   | > cannot be keep  | > nurse educator. |
|         |                   | > down for more   |                   |
|         |                   | > than 6 hours    |                   |
|         |                   | > consider it a   |                   |
|         |                   | > knowledge       |                   |
|         |                   | > deficit.        |                   |
+---------+-------------------+-------------------+-------------------+

+---------+-------------------+-------------------+-------------------+
| **Tr    | **Questions to    | **Patient         | **Suggested       |
| eatment | Ask\              | Response**        | Actions**         |
| Plan &  | **                |                   |                   |
| Goals** |                   |                   | **to be Taken**   |
+---------+-------------------+-------------------+-------------------+
| **Acute | 1.  Do you know   | Consider it a     | Educate patient   |
| C       |     what to do    | knowledge deficit | on:               |
| omplica |     when your     | if the patient is |                   |
| tions** |     sugars are    | unable to         | 1.  Signs and     |
|         |     low or high,  | verbalize:        |     symptoms of   |
|         |     and when to   |                   |     hyper/        |
|         |     call your     | 1.  When the      |     hypoglycemia; |
|         |     health care   |     blood sugar   |                   |
|         |     provider?     |     is low he/she | 2.  Calling their |
|         |                   |     should eat or |     health care   |
|         |                   |     drink 15-20 g |     provider when |
|         |                   |     of fast       |     they have     |
|         |                   |     acting        |     repeated      |
|         |                   |     carbohydrate  |     episodes of   |
|         |                   |     (CHO) food or |     unexplainable |
|         |                   |     fluid.        |     hy            |
|         |                   |                   | per/hypoglycemia. |
|         |                   | 2.  If BS is high |                   |
|         |                   |     he or she     | Assess for        |
|         |                   |     should know   | barriers to care/ |
|         |                   |     when or if to | self management:  |
|         |                   |     increase      |                   |
|         |                   |     medication,   | 1.  Financial;    |
|         |                   |     to increase   |                   |
|         |                   |     the frequency | 2.  Social;       |
|         |                   |     of SMG, to    |                   |
|         |                   |     call primary  | 3.  Psychiatric;  |
|         |                   |     care provider |                   |
|         |                   |     with results, | 4.  Nutritional;  |
|         |                   |     and to drink  |                   |
|         |                   |     large amounts | 5.  Health        |
|         |                   |     of sugar free |     beliefs;      |
|         |                   |     fluids.       |                   |
|         |                   |                   | 6.  Cultural      |
|         |                   |                   |     differences;  |
|         |                   |                   |                   |
|         |                   |                   | 7.  Language      |
|         |                   |                   |     difficulties. |
|         |                   |                   |                   |
|         |                   |                   | Refer if:         |
|         |                   |                   |                   |
|         |                   |                   | 1.  Specific      |
|         |                   |                   |     need/ barrier |
|         |                   |                   |     to learning   |
|         |                   |                   |     has been      |
|         |                   |                   |     identified    |
|         |                   |                   |     which does    |
|         |                   |                   |     not allow the |
|         |                   |                   |     patient to    |
|         |                   |                   |     perform       |
|         |                   |                   |                   |
|         |                   |                   |  self-management. |
|         |                   |                   |     This need may |
|         |                   |                   |     be addressed  |
|         |                   |                   |     with an       |
|         |                   |                   |     individual    |
|         |                   |                   |     consultation; |
|         |                   |                   |                   |
|         |                   |                   | 2.  If a specific |
|         |                   |                   |     barrier has   |
|         |                   |                   |     not been      |
|         |                   |                   |     identified or |
|         |                   |                   |     more than one |
|         |                   |                   |     need/barrier  |
|         |                   |                   |     is            |
|         |                   |                   |     identified,   |
|         |                   |                   |     referral to a |
|         |                   |                   |     comprehensive |
|         |                   |                   |     diabetes      |
|         |                   |                   |     education     |
|         |                   |                   |     program is    |
|         |                   |                   |     recommended.  |
+---------+-------------------+-------------------+-------------------+
| **      | 1.  Are there any | If patient        | Address this      |
| Psychos |     problems in   | responds with     | issue in Primary  |
| ocial** |     your life     | symptoms of       | Care setting and  |
|         |     that make it  | depression,       | educate if        |
|         |     difficult for | denial, or anger  | appropriate.      |
|         |     you to take   | that interferes   |                   |
|         |     care of your  | with              | Otherwise, refer  |
|         |     diabetes?     | self-management,  | to Behavioral     |
|         |                   | consider those    | Medicine for      |
|         | 2.  Are you       | indicative of     | evaluation and    |
|         |     overwhelmed   | psychosocial      | counseling.       |
|         |     with your     | issues.           |                   |
|         |     diabetes?     |                   |                   |
|         |                   | .                 |                   |
|         | 3.  3\. Do you    |                   |                   |
|         |     worry about   |                   |                   |
|         |     developing    |                   |                   |
|         |     complications |                   |                   |
|         |     of diabetes?  |                   |                   |
+---------+-------------------+-------------------+-------------------+
| **Pre   | 1.  Do you know   | Consider it a     | Educate on        |
| ventive |     why you have  | knowledge deficit | importance of     |
| Scre    |     to have a     | if patient is     | annual eye exam   |
| ening** |     periodic eye  | unable to         | to identify       |
|         |     exam?         | verbalize         | changes early so  |
|         |                   | importance of eye | treatment can be  |
|         | 2.  Have you      | examinations to   | initiated before  |
|         |     scheduled     | prevent blindness | irreversible      |
|         |     your annual   | and identify      | damage occurs.    |
|         |     eye and foot  | changes in        |                   |
|         |     examinations? | vision.           | Facilitate        |
|         |                   |                   | scheduling of     |
|         |                   | Consider it a     | appropriate exam. |
|         |                   | knowledge deficit |                   |
|         |                   | if patient does   |                   |
|         |                   | not verbalize     |                   |
|         |                   | need and/or       |                   |
|         |                   | intent to         |                   |
|         |                   | schedule visit.   |                   |
+---------+-------------------+-------------------+-------------------+

+---------+-------------------+-------------------+-------------------+
| **Tr    | **Questions to    | **Patient         | **Suggested       |
| eatment | Ask\              | Response**        | Actions**         |
| Plan &  | **                |                   |                   |
| Goals** |                   |                   | **to be Taken**   |
+---------+-------------------+-------------------+-------------------+
| **Tr    | 1.  Is there      | If patient        | If primary care   |
| eatment |     anything that | identifies a      | staff has         |
| Adhe    |     has been      | specific area of  | adequate time to  |
| rence** |     recommended   | concern (e.g.,    | address areas of  |
|         |     that you do   | diet, blood sugar | concern then      |
|         |     for your      | testing), select  | identify          |
|         |     diabetes that | appropriate       | barriers,         |
|         |     you think you | questions to      | potential         |
|         |     will have     | determine if      | solutions, and    |
|         |     difficulty    | patient has       | develop plan.     |
|         |     with, or are  | knowledge of how  |                   |
|         |     unable to do? | to self-manage    | Evaluate barriers |
|         |                   | diabetes.         | and engage        |
|         | *Or*              | Consider the      | patient in        |
|         |                   | possibility of    | identifying       |
|         | 2.  What part of  | knowledge deficit | potential         |
|         |     diabetes      | or psychosocial   | self-management   |
|         |     treatment do  | of issues.        | goals to overcome |
|         |     you have      |                   | barriers.         |
|         |     difficulty    |                   |                   |
|         |     with?         |                   | If time does not  |
|         |                   |                   | permit, schedule  |
|         |                   |                   | another           |
|         |                   |                   | appointment,      |
|         |                   |                   | refer to CDE or   |
|         |                   |                   | specialist in     |
|         |                   |                   | area of concern   |
|         |                   |                   | to address        |
|         |                   |                   | barriers or refer |
|         |                   |                   | to comprehensive  |
|         |                   |                   | self-management   |
|         |                   |                   | program (see      |
|         |                   |                   | Appendix 1).      |
+---------+-------------------+-------------------+-------------------+
| # Li    | 1.  How do        | If patient is     | Address areas of  |
| festyle |     alcohol and   | unable to         | concern, and      |
|         |     cigarettes    | verbalize that    | provide           |
|         |     affect your   | alcohol increases | prevention        |
|         |     diabetes?     | weight, can cause | education. Refer  |
|         |                   | severe            | if indicated. If  |
|         | 2.  Do you want   | hypoglycemia; and | time does not     |
|         |     to get        | smoking           | permit, schedule  |
|         |     pregnant-     | cigarettes causes | another           |
|         |     either now or | poor circulation  | appointment,      |
|         |     in the near   | and contributes   | refer to CDE, or  |
|         |     future?       | to HTN and        | specialist in     |
|         |                   | macrovascular     | area of concern.  |
|         | 3.  If you are    | disease, then     |                   |
|         |     sexually      | knowledge deficit | Refer to Ob-Gyn   |
|         |     active, what  | exists.           | or appropriate    |
|         |     contraception |                   | clinician that    |
|         |     methods are   | If patient        | specializes in    |
|         |     you using?    | response Yes then | reproductive      |
|         |                   | additional        | counselling for   |
|         | 4.  Have there    | knowledge is      | persons with      |
|         |     been any      | required---refer. | diabetes.         |
|         |     major changes |                   |                   |
|         |     in your life? | If patient is     | (See above)       |
|         |                   | unable to         |                   |
|         |                   | verbalize         | Refer to          |
|         |                   | adequate          | appropriate       |
|         |                   | contraceptive     | person to address |
|         |                   | methods then      | these issues or   |
|         |                   | consider as       | determine effect  |
|         |                   | indication for    | of changes on     |
|         |                   | additional        | ability to meet   |
|         |                   | interventions/    | diabetes          |
|         |                   | counselling.      | treatment goals   |
|         |                   |                   | (e.g., shift      |
|         |                   | If patient        | changes and       |
|         |                   | indicates yes,    | medication/diet   |
|         |                   | consider as       | adjustments,      |
|         |                   | indication that   | spouse no longer  |
|         |                   | psychosocial      | doing cooking and |
|         |                   | issues are of     | patient has not   |
|         |                   | concern.          | done this in the  |
|         |                   |                   | past).            |
+---------+-------------------+-------------------+-------------------+

EVIDENCE

DCCT 1997. LE = I, SR = A; UKPDS 1998. LE = I, SR = A

Resource: A Core Curriculum for Diabetes Education, third edition,
American Association of Diabetes Educators, 1998

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

#### Appendix M7. List of Patient References: Diabetes Resources

ORGANIZATIONS

**American Diabetes Association**

> 1660 Duke Street
>
> Alexandria, VA 22314
>
> \(703\) 549-1500 National Center
>
> \(800\) 232-6733 Publications
>
> \(800\) DIABETES (342-2383) for information about diabetes

**The American Dietetic Association**

> 216 West Jackson Blvd., Suite 800
>
> Chicago, IL 60606-6995
>
> Call (800) 366-1655 to speak with a dietitian, find a dietitian, or
> order free information.

**American Association of Diabetes Educators**

> 100 West Monroe, Suite 400
>
> Chicago, IL 60603
>
> \(800\) 338-3633 Association number
>
> Call (800) TEAM-UP4 for a 24-hour opportunity to speak with a diabetes
> educator.

EDUCATIONAL MATERIAL

**National Diabetes Information Clearinghouse (NDIC)**

> 1 Information Way
>
> Bethesda, MD 20892
>
> \(301\) 654-3327
>
> (3010 907-8906 (FAX)

PRINTED INFORMATION

**American Diabetes Association**

> Publication Orders
>
> \(800\) 232-6733

JOURNALS FOR PEOPLE WITH DIABETES

**Diabetes Advisor** (bimonthly newsletter)

> American Diabetes Association
>
> \(800\) 806-7802

**Diabetes Forecast** (monthly magazine)

> Subscription included with American Diabetes Association membership.
>
> \(800\) 806-7801

**Diabetes Self-Management (monthly subscription magazine)**

> \(800\) 234-0923

DIABETES NEWSLETTERS

**Diabetes Control Network**

> \(800\) DCN-5554

**Diabetes Wellness Letter**

> P.O. Box 3837
>
> Merrifield, VA 22116

INTERNET RESOURCES

**American Diabetes Association (ADA):**
[http://www.diabetes.org]{.underline}

> Lists association events, daily menu, publication ordering, and
> selected articles from ADA publications.

**National Institute of Diabetes and Digestive and Kidney Disease
(NIDDK):** [p://www.niddk.nih.gov/]{.underline}h[tt]{.underline}

> Information about research, statistics, questions to ask your doctor,
> and directory of diabetes organizations.

**Juvenile Diabetes Foundation International (JDF):**
[http://www.jdfcure.com]{.underline}

**Division of Diabetes Translation at Centers for Disease Control and
Prevention (CDC)**

> National Diabetes Education Program at
> <http://www.cdc.gov/nccdphp/ddt/ddthome.htm>

**Department of Veterans Health Affairs:** http://www.va.gov/

# MANAGEMENT OF DIABETES MELLITUS IN THE PRIMARY CARE SETTING

# 

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