bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Sensitivity in the Offspring of Women With Type 1 and Type 2 Diabetes
Authors: Hunter Wendy A. , Cundy Tim , Rabone Diana , Hofman Paul L. , Harris Mark , Regan Fiona , Robinson Elizabeth , Cutfield Wayne S.
Published: March 2007

OBJECTIVE—To determine if insulin sensitivity is altered in prepubertal offspring exposed to a diabetic intrauterine environment.

RESEARCH DESIGN AND METHODS—Fifteen control children, 17 offspring of type 1 diabetic women, and 10 offspring of type 2 diabetic women, aged between 5 and 10 years, underwent a frequently sampled intravenous glucose tolerance test (FSIGTT). Weight and height were measured, and body composition was calculated using bioelectrical impedance. Bergman’s minimal model was applied to the glucose and insulin measurements to obtain values for insulin sensitivity (Si), acute insulin response (AIR), and glucose effectiveness (Sg).

RESULTS—Si was lowest in the offspring of type 2 diabetic mothers, and AIR was highest in this group, although neither of these changes reached significance (Si, P = 0.2, and AIR, P = 0.3). Offspring of type 2 diabetic mothers had higher BMI SD scores (P = 0.004) and percentage fat mass (P = 0.002) than the children in the other two groups. The BMI SD score and percentage fat mass in the subjects, as well as maternal insulin dose, were negatively correlated with offspring insulin sensitivity.

CONCLUSIONS—Intrauterine exposure to hyperglycemia by itself was not associated with alterations in glucose regulation in prepubertal offspring. Children of mothers with type 2 diabetes, however, were overweight, and they had a tendency for a reduced Si. The combined effect of genetic and postnatal environmental factors, rather than prenatal exposure to hyperglycemia, may place this group at risk for developing impaired glucose tolerance in later life.
Younger Age at Onset and Sex Predict Celiac Disease in Children and Adolescents With Type 1 Diabetes
Authors: Cerutti Franco , Bruno Graziella , Chiarelli Francesco , Lorini Renata , Meschi Franco , Sacchetti Carla ,   the Diabetes Study Group of Italian Society of Pediatric Endocrinology and Diabetology
Published: March 2007

OBJECTIVE—To estimate the prevalence of biopsy-confirmed celiac disease in Italian children and adolescents with type 1 diabetes and to assess whether age at onset of type 1 diabetes is independently associated with diagnosis of celiac disease.

RESEARCH DESIGN AND METHODS—The study group was a clinic-based cohort of children and adolescents with type 1 diabetes cared for in 25 Italian centers for childhood diabetes. Yearly screening for celiac disease was performed using IgA/IgG anti-gliadin and IgA anti-endomysium antibodies.

RESULTS—Of the 4,322 children and adolescents (age 11.8 ± 4.2 years) identified with type 1 diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%, 95% confidence interval [CI] 6.0–7.6), with a higher risk seen in girls than in boys (odds ratio [OR] 1.93, 1.51–2.47). In 89% of these, diabetes was diagnosed before celiac disease. In logistic regression analyses, being younger at onset of diabetes, being female, and having a diagnosis of a thyroid disorder were independently associated with the risk of having diabetes and celiac disease. In comparison with subjects who were older than 9 years at onset of diabetes, subjects who were younger than 4 years at onset had an OR of 3.27 (2.20–4.85).

CONCLUSIONS—We have provided evidence that 1) the prevalence of biopsy-confirmed celiac disease in children and adolescents with type 1 diabetes is high (6.8%); 2) the risk of having both diseases is threefold higher in children diagnosed with type 1 diabetes at age <4 years than in those age >9 years; and 3) girls have a higher risk of having both diseases than boys.
Clinical Characteristics of Children Diagnosed With Type 1 Diabetes Through Intensive Screening and Follow-Up
Authors: Barker Jennifer M. , Goehrig Stephanie H. , Barriga Katherine , Hoffman Michelle , Slover Robert , Eisenbarth George S. , Norris Jill M. , Klingensmith Georgeanna J. , Rewers Marian
Published: March 2007

OBJECTIVE—The objective of this study was to determine whether earlier diagnosis of diabetes in prospectively followed autoantibody-positive children lowered onset morbidity and improved the clinical course after diagnosis.

RESEARCH DESIGN AND METHODS—The Diabetes Autoimmunity Study in the Young (DAISY) follows genetically at-risk children for the development of diabetes. Increased genetic risk is identified by family history of type 1 diabetes or expression of diabetes-associated HLA genotypes. Of the 2,140 prospectively followed children, 112 have developed islet autoantibodies and 30 have progressed to diabetes. Diabetes onset characteristics and early clinical course of these 30 children followed to diabetes were compared with those of 101 age- and sex-matched children concurrently diagnosed with diabetes in the community.

RESULTS—Pre-diabetic children followed to diabetes were less often hospitalized than the community cases (3.3 vs. 44%; P < 0.0001). They had a lower mean HbA1c at onset (7.2 vs. 10.9%; P < 0.0001) and 1 month after diagnosis (6.9 vs. 8.6%; P < 0.0001) but not after 6 months of diabetes. The mean insulin dose was lower in the DAISY group at 1 (0.30 vs. 0.51 U · kg−1 · day−1; P = 0.003), 6 (0.37 vs. 0.58; P = 0.001), and 12 months (0.57 vs. 0.72; P = 0.03). There was no difference in growth parameters between the two groups. Comparisons limited to children with a family history of type 1 diabetes in both groups showed a similar pattern.

CONCLUSIONS—Childhood type 1 diabetes diagnosed through a screening and follow-up program has a less severe onset and a milder clinical course in the first year after diagnosis.
Lipids and Lipoproteins in Patients With Type 2 Diabetes
Authors: Krauss Ronald M.
Published: March 2007

Insulin resistance and type 2 diabetes are associated with a clustering of interrelated plasma lipid and lipoprotein abnormalities, which include reduced HDL cholesterol, a predominance of small dense LDL particles, and elevated triglyceride levels. Each of these dyslipidemic features is associated with an increased risk of cardiovascular disease. Increased hepatic secretion of large triglyceride-rich VLDL and impaired clearance of VLDL appears to be of central importance in the pathophysiology of this dyslipidemia. Small dense LDL particles arise from the intravascular processing of specific larger VLDL precursors. Typically, reduced plasma HDL levels in type 2 diabetes are manifest as reductions in the HDL2b subspecies and relative or absolute increases in smaller denser HDL3b and HDL3c. Although behavioral interventions such as diet and exercise can improve diabetic dyslipidemia, for most patients, pharmacological therapy is needed to reach treatment goals. There are several classes of medications that can be used to treat lipid and lipoprotein abnormalities associated with insulin resistance and type 2 diabetes, including statins, fibrates, niacin, and thiazolidinediones. Clinical trials have shown significant improvement in coronary artery disease after diabetic dyslipidemia treatment.
Managed Care Organization and the Quality of Diabetes Care
Authors: Kim Catherine , Williamson David F. , Mangione Carol M. , Safford Monika M. , Selby Joseph V. , Marrero David G. , Curb J. David , Thompson Theodore J. , Venkat Narayan K.M. , Herman William H. ,   the TRIAD Study Group
Published: March 2007

OBJECTIVE—To examine the association between the organizational model and diabetes processes of care.

RESEARCH DESIGN AND METHODS—We used data from the Translating Research into Action for Diabetes (TRIAD), a multicenter study of diabetes care in managed care, including 8,354 patients with diabetes. We identified five model types: for-profit group/network, for-profit independent practice association (IPA), nonprofit group/network, nonprofit IPA, and nonprofit group/staff. Process measures included retinal, renal, foot, lipid, and HbA1c testing; aspirin recommendations; influenza vaccination; and a sum of these seven processes of care over 1 year. Hierarchical regression models were constructed for each process measure and accounted for clustering at the health plan and provider group levels and adjusted for participant age, sex, race, ethnicity, diabetes treatment and duration, education, income, health status, and survey language.

RESULTS—Participant membership in the model types ranged from 9% in nonprofit IPA models to 38% in nonprofit group/staff models. Over 75% of participants received most of the processes of care, regardless of model type. However, among for-profit plans, group/network models provided on average more processes of care than IPA models (5.5 vs. 4.7, P < 0.0001), and group/network models generally increased the probability of receiving a process by ≥10 percentage points. Among nonprofit plans, no effect of model type was found.

CONCLUSIONS—Among for-profit plans, group/network models provided better diabetes processes of care than IPA models. Although reasons are speculative, this may be due to the clinical infrastructure available in group models that is not available in IPA models.
Cerebral Edema in Childhood Diabetic Ketoacidosis
Authors: Muir Andrew B. , Quisling Ronald G. , Yang Mark C.K. , Rosenbloom Arlan L.
Published: March 2007

OBJECTIVE—Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA.

RESEARCH DESIGN AND METHODS—A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed. Signs of neurological disease were incorporated into a bedside evaluation protocol that was applied to an independent test sample of 17 patients previously reported to have developed symptomatic CE during treatment for DKA. Head computed tomograms and their reports were reviewed.

RESULTS—The protocol allowed 92% sensitivity and 96% specificity for the recognition of CE sufficiently early for intervention. The diagnostic criteria were fulfilled in two temporal patterns, defining early- and late-onset CE. Although initial computed tomograms were often normal, the findings also included diffuse CE and focal brain injury, the latter only in patients with an early onset of abnormal neurological signs.

CONCLUSIONS—CE may occur in the absence of acute changes on head computed tomograms. Early detection of CE at the bedside using an evidence-based protocol permits intervention in time to prevent permanent brain damage.
A Randomized, Prospective Trial Comparing the Efficacy of Continuous Subcutaneous Insulin Infusion With Multiple Daily Injections Using Insulin Glargine
Authors: Doyle (Boland) Elizabeth A. , Weinzimer Stuart A. , Steffen Amy T. , Ahern Jo Ann H. , Vincent Miranda , Tamborlane William V.
Published: March 2007

OBJECTIVE—The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA1c levels in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Thirty-two youth with type 1 diabetes (age 8–21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA1c. HbA1c, total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy.

RESULTS—While there was no significant change in the glargine group (HbA1c 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA1c levels, from 8.1 to 7.2% after 16 weeks of therapy (P < 0.02 vs. baseline and <0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P < 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P < 0.01).

CONCLUSIONS—Lower HbA1c and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes.
Effectiveness of Diabetic Therapeutic Footwear in Preventing Reulceration
Authors: Maciejewski Matthew L. , Reiber Gayle E. , Smith Douglas G. , Wallace Carolyn , Hayes Shane , Boyko Edward J.
Published: March 2007

OBJECTIVE—To review the evidence for the effectiveness of therapeutic footwear in preventing foot reulceration in individuals with diabetes and foot risk factors.

RESEARCH DESIGN AND METHODS—We conducted a structured literature review based on a Medline search for studies of therapeutic footwear that examined prevention of reulceration. Nine published articles were identified. Characteristics of the study population, components of the intervention, and level of adherence were evaluated. U.S. Preventive Services Task Force criteria for evaluating research were applied to rate each study on study design and internal validity.

RESULTS—Risk ratios in all studies assessing the association between therapeutic footwear and reulceration were below 1.0, suggesting some protective footwear benefit. However, in the most rigorous experimental study, no statistically significant benefit was observed between control patients wearing their own footwear and intervention patients wearing study footwear. Annual reulceration in these studies’ control groups ranged from 8.4 to 59.3%. In patients with severe foot deformity or prior toe or ray amputation, observational studies suggested a significant protective benefit from therapeutic footwear.

CONCLUSIONS—Therapeutic footwear has been used for decades as one of many strategies to prevent reulceration in patients with diabetes and foot risk factors. The findings of several studies reporting statistically significant protective effects from therapeutic footwear may have been influenced by several design issues. When considering the appropriateness of therapeutic footwear recommendations for moderate-risk patients, clinicians and patients should jointly explore individual strategies to decrease events that lead to foot ulcers.
Circulating 1,5-Anhydroglucitol Levels in Adult Patients With Diabetes Reflect Longitudinal Changes of Glycemia
Authors: McGill Janet B. , Cole Thomas G. , Nowatzke William , Houghton Shannon , Ammirati Erika B. , Gautille Theresa , Sarno Mark J.
Published: March 2007

OBJECTIVE—1,5-Anhydroglucitol (1,5AG) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose. Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies. In this first U.S. study, we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes (22 with type 1 diabetes, 55 with type 2 diabetes) who presented with suboptimal glycemic control at baseline (defined as HbA1c ≥7%).

RESEARCH DESIGN AND METHODS—Each patient received therapies consisting of combinations of diabetes education, nutritional counseling, and addition or dose adjustment of various insulins or oral antihyperglycemic medications. Therapy was targeted to reduce mean HbA1c by ≥1.0% over the monitoring period. 1,5AG, HbA1c, fructosamine, and random glucose measurements were performed at baseline and at 2, 4, and 8 weeks after the initiation of therapy.

RESULTS—1,5AG, fructosamine, and glucose values progressed significantly toward euglycemia by week 2 of monitoring (Wilcoxon’s signed-rank test, P < 0.05), with median changes of 93, −7, and −13% for 1,5AG, fructosamine, and glucose, respectively. In contrast, HbA1c values did not respond significantly to therapy until week 4. On an individual patient basis, 89.6% of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA1c. 1,5AG was also highly correlated with HbA1c and fructosamine (Spearman ρ = −0.6459 and −0.6751, respectively; both P < 0.0001).

CONCLUSIONS—We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers.
Improved Plasma Glucose Control, Whole-Body Glucose Utilization, and Lipid Profile on a Low-Glycemic Index Diet in Type 2 Diabetic Men
Authors: Rizkalla Salwa W. , Taghrid Laika , Laromiguiere Muriel , Huet Dorothée , Boillot Josette , Rigoir Aude , Elgrably Fabienne , Slama Gerard
Published: March 2007

OBJECTIVE—To determine whether a chronic low-glycemic index (LGI) diet, compared with a high-glycemic index (HGI) diet, has beneficial effects on plasma glucose control, lipid metabolism, total fat mass, and insulin resistance in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Twelve type 2 diabetic men were randomly allocated to two periods of 4 weeks of an LGI or HGI carbohydrate diet separated by a 4-week washout interval, in a crossover design.

RESULTS—The LGI diet induced lower postprandial plasma glucose and insulin profiles and areas under the curve than after the HGI diet. At the end of the two dietary periods, the 7-day dietary records demonstrated equal daily total energy and macronutrient intake. Body weight and total fat mass were comparable. Four-week LGI versus HGI diet induced improvement of fasting plasma glucose (P < 0.01, Δ changes during LGI vs. HGI), HbA1c (P < 0.01), and whole-body glucose utilization measured by the euglycemic-hyperinsulinemic clamp (P < 0.05). LGI diet induced a decrease in fasting plasma total and LDL cholesterol (Δ changes LGI vs. HGI, P < 0.01), free fatty acids (P < 0.01), apolipoprotein B, and plasminogen activator inhibitor 1 activity.

CONCLUSIONS—Only 4 weeks of an LGI diet was able to improve glycemic control, glucose utilization, some lipid profiles, and the capacity for fibrinolysis in type 2 diabetes. Even if changes in glycemic control were modest during the 4-week period, the use of an LGI diet in a longer-term manner might play an important role in the treatment and prevention of diabetes and related disorders.
Additive Effects of Glucagon-Like Peptide 1 and Pioglitazone in Patients With Type 2 Diabetes
Authors: Zander Mette , Christiansen Allan , Madsbad Sten , Juul Holst Jens
Published: March 2007

OBJECTIVE—To evaluate the effect of combination therapy with pioglitazone and glucagon-like peptide (GLP)-1 in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Eight patients with type 2 diabetes (BMI 32.7 ± 1.3 kg/m2 and fasting plasma glucose 13.5 ± 1.2 mmol/l) underwent four different treatment regimens in random order: saline therapy, monotherapy with continuous subcutaneous infusion of GLP-1 (4.8 pmol · kg−1 · min−1), monotherapy with pioglitazone (30-mg tablet of Actos), and combination therapy with GLP-1 and pioglitazone. The observation period was 48 h. End points were plasma levels of glucose, insulin, glucagon, free fatty acids (FFAs), and sensation of appetite.

RESULTS—Fasting plasma glucose decreased from 13.5 ± 1.2 mmol/l (saline) to 11.7 ± 1.2 (GLP-1) and 11.5 ± 1.2 (pioglitazone) and further decreased to 9.9 ± 1.0 (combination) (P < 0.001). Eight-hour mean plasma glucose levels were reduced from 13.7 ± 1.1 mmol/l (saline) to 10.6 ± 1.0 (GLP-1) and 12.0 ± 1.2 (pioglitazone) and were further reduced to 9.5 ± 0.8 (combination) (P < 0.0001). Insulin levels increased during monotherapy with GLP-1 compared with monotherapy with pioglitazone (P < 0.01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P < 0.01). FFAs during breakfast (area under the curve, 0–3 h) were reduced in combination therapy compared with saline (P = 0.03). Sensation of appetite was reduced during monotherapy with GLP-1 and combination therapy (P < 0.05).

CONCLUSIONS—GLP-1 and pioglitazone show an additive glucose-lowering effect. A combination of the two agents may, therefore, be a valuable therapeutic approach for the treatment of type 2 diabetes.
Evaluating the Accuracy of Continuous Glucose-Monitoring Sensors
Authors: Kovatchev Boris P. , Gonder-Frederick Linda A. , Cox Daniel J. , Clarke William L.
Published: March 2007

OBJECTIVE—The objective of this study was to introduce continuous glucose–error grid analysis (CG-EGA) as a method of evaluating the accuracy of continuous glucose-monitoring sensors in terms of both accurate blood glucose (BG) values and accurate direction and rate of BG fluctuations and to illustrate the application of CG-EGA with data from the TheraSense Freestyle Navigator.

RESEARCH DESIGN AND METHODS—We approach the design of CG-EGA from the understanding that continuous glucose sensors (CGSs) allow the observation of BG fluctuations as a process in time. We account for specifics of process characterization (location, speed, and direction) and for biological limitations of the observed processes (time lags associated with interstitial sensors). CG-EGA includes two interacting components: 1) point–error grid analysis (P-EGA) evaluates the sensor’s accuracy in terms of correct presentation of BG values and 2) rate–error grid analysis (R-EGA) assesses the sensor’s ability to capture the direction and rate of BG fluctuations.

RESULTS—CG-EGA revealed that the accuracy of the Navigator, measured as a percentage of accurate readings plus benign errors, was significantly different at hypoglycemia (73.5%), euglycemia (99%), and hyperglycemia (95.4%). Failure to detect hypoglycemia was the most common error. The point accuracy of the Navigator was relatively stable over a wide range of BG rates of change, and its rate accuracy decreased significantly at high BG levels.

CONCLUSIONS—Traditional self-monitoring of BG device evaluation methods fail to capture the important temporal characteristics of the continuous glucose-monitoring process. CG-EGA addresses this problem, thus providing a comprehensive assessment of sensor accuracy that appears to be a useful adjunct to other CGS performance measures.
Female Children and Adolescents With Type 1 Diabetes Have More Pronounced Early Echocardiographic Signs of Diabetic Cardiomyopathy
Authors: Suys Bert E. , Katier Nienke , Rooman Raoul P.A. , Matthys Dirk , Op De Beeck Lieve , Du Caju Mark V.L. , De Wolf Daniel
Published: March 2007

OBJECTIVE—This study was designed to assess whether children and adolescents with type 1 diabetes have early echocardiographic signs of subclinical cardiac dysfunction and whether sex, state of metabolic control, and diabetes duration are of influence.

RESEARCH DESIGN AND METHODS—Systolic and diastolic blood pressure in supine and upright positions and echocardiographic parameters, including tissue Doppler measurements of the septal mitral annulus, were evaluated in 80 children and adolescents with stable type 1 diabetes and 52 age- and sex-matched control subjects. A possible correlation was examined for age, sex, HbA1c, and diabetes duration with univariate and multivariate regression analysis.

RESULTS—Female diabetic patients showed significantly larger left ventricular wall dimensions (left ventricular posterior wall in diastole 0.54 ± 0.08 vs. 0.48 ± 0.11 cm) and signs of significant diastolic filling abnormalities on conventional and tissue Doppler echocardiography (mitral valve-atrial contraction velocity 0.47 ± 0.12 vs. 0.40 ± 0.09 m/s; tricuspid valve-atrial contraction velocity 0.35 ± 0.09 vs. 0.30 ± 0.07 m/s; early filling velocity/myocardial velocity during early filling 7.15 ± 1.47 vs. 6.17 ± 1.07; isovolumetric relaxation time [IVRT] 66 ± 8 vs. 58 ± 8 ms) compared with female control subjects, suggesting delayed myocardial relaxation. Male diabetic patients only differed significantly from their control subjects for IVRT (66 ± 9 vs. 59 ± 8 ms). The measured parameters showed an expected correlation with age and BMI standard deviation scores in the control group. This correlation was significantly weaker in the diabetic population; only a weak influence was found for diabetes duration and glycosylated hemoglobin levels.

CONCLUSIONS—Young diabetic patients already have significant changes in left ventricular dimensions and myocardial relaxation, with the girls clearly being more affected. Tissue Doppler proved to have additional value in the evaluation of ventricular filling in this population. Almost no correlation was found for diabetes duration and HbA1c with the cardiovascular changes.
Intraepidermal Nerve Fibers Are Indicators of Small-Fiber Neuropathy in Both Diabetic and Nondiabetic Patients
Authors: Pittenger Gary L. , Ray Madhumita , Burcus Niculina I. , McNulty Patricia , Basta Baher , Vinik Aaron I.
Published: March 2007

OBJECTIVE—Small-fiber neuropathies may be symptomatic yet escape detection by standard tests. We hypothesized that morphologic changes in intraepidermal nerves would correlate with clinical measures of small-fiber neuropathy.

RESEARCH DESIGN AND METHODS—We studied 25 diabetic and 23 nondiabetic patients with neuropathy defined by signs, symptoms, and quantitative testing and 20 control subjects. Skin biopsies were obtained from forearm, thigh, proximal leg, and distal leg, and nerves identified using immunofluorescence with antibody to protein gene product (PGP) 9.5.

RESULTS—Mean dendritic length (MDL) (P < 0.01) and intraepidermal nerve fiber density (IENF) (P < 0.001) progressively decreased from proximal to distal sites only in patients with neuropathy. There was a significant reduction in IENF when comparing control subjects and patient groups in the distal leg (P < 0.001). MDL was significantly decreased in the thigh (P < 0.005) and in the proximal (P < 0.01) and distal (P < 0.002) leg in patients compared with control subjects. IENF was not significantly altered in diabetic patients of <5 years’ duration, but significantly decreased in patients with >5 years’ duration. MDL showed a linear decrease with increasing duration of diabetes. Distal leg IENF showed significant negative correlations with warm (P < 0.02) and cold (P < 0.05) thermal threshold, heat pain (P < 0.05), pressure sense (P < 0.05), and neurological disability score total sensory (P < 0.03) and total neuropathy (P < 0.03) values.

CONCLUSIONS—IENF was not significantly altered in these patients at <5 years’ duration of diabetes, but fell significantly after 5 years of diabetes. MDL exhibited a linear loss with time, suggesting a different mechanism of change. MDL and IENF together may prove a useful end point in therapeutic trials for neuropathy.
Inflammation, Insulin Resistance, and Adiposity
Authors: Kriketos Adamandia D. , Greenfield Jerry R. , Peake Phil W. , Furler Stuart M. , Denyer Gareth S. , Charlesworth John A. , Campbell Lesley V.
Published: March 2007

OBJECTIVE—Inflammatory markers such as C-reactive protein (CRP) are associated with insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity.

RESEARCH DESIGN AND METHODS—We studied 19 young normoglycemic nonobese first-degree relatives of type 2 diabetic subjects and 22 control subjects who were similar for age, sex, and BMI. Insulin sensitivity (glucose infusion rate [GIR]) was measured by the euglycemic-hyperinsulinemic clamp. Dual-energy X-ray absorptiometry determined total and abdominal adiposity. Magnetic resonance imaging measured abdominal adipose tissue volumes.

RESULTS—First-degree relatives of type 2 diabetic subjects had a 20% lower GIR than the control group (51.8 ± 3.9 vs. 64.9 ± 4.6 μmol · min−1 · kg fat-free mass−1, P = 0.04). However, first-degree relatives of subjects with type 2 diabetes and those without a family history of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins. When the cohort was examined as a whole, CRP was inversely related to GIR (r = −0.33, P = 0.04) and adiponectin (r = −0.34, P = 0.03) and positively related to adiposity (P < 0.04). However, CRP was not related to GIR independently of fat mass. In contrast to C3 (r = 0.41, P = 0.009) and factor B (r = 0.43, P = 0.005), CRP was unrelated to factor D.

CONCLUSIONS—The insulin-resistant state is not associated with changes in inflammatory markers or complement proteins in subjects at high risk of type 2 diabetes. Our study confirms a strong relationship between CRP and fat mass. Increasing adiposity and insulin resistance may interact to raise CRP levels.
Haptoglobin Phenotype and Gestational Diabetes
Authors: Mustafa Stefan , Vukovich Thomas , Prikoszovich Thomas , Winzer Christine , Schneider Barbara , Esterbauer Harald , Wagner Oswald , Kautzky-Willer Alexandra
Published: March 2007

OBJECTIVE—Haptoglobin (Hp), an Hb-binding plasma protein, exists in two major allelic variants. Hp1 has higher Hb binding and antioxidant capacity compared with Hp2. Individuals with Hp1 exhibit a lower incidence of angiopathies. Gestational diabetes mellitus (GDM) is an early manifestation of type 2 diabetes in pregnant women. It is usually confined to the time of gestation, but carries an increased risk to develop type 2 diabetes later in life.

RESEARCH DESIGN AND METHODS—From consecutive Caucasian pregnant women (n = 250) referred for oral glucose tolerance testing, the Hp phenotype was determined. Significance of distribution and odds ratios (ORs) associated with Hp phenotype were calculated for women with GDM (n = 110) and women with normal glucose tolerance (n = 140).

RESULTS—Frequency of GDM in Hp phenotype classes increased with the number of Hp2 alleles (P < 0.001). ORs for GDM in women heterozygous and homozygous for Hp2 were 2.7 (95% CI 1.06–6.84) and 4.2 (1.67–10.55), respectively.

CONCLUSIONS—Hp phenotype is an apparent risk factor for the development of GDM in our study population. This might be due to the low antioxidative potential of Hp2 compared with Hp1.
Hepatitis C Infection and Type 2 Diabetes in American-Indian Women
Authors: Wilson Charlton
Published: March 2007

OBJECTIVE—The aim of this study was to describe the association between hepatitis C virus (HCV) infection and type 2 diabetes among a group of American-Indian women who were screened for both conditions.

RESEARCH DESIGN AND METHODS—The study population was a convenience sample of women who were receiving prenatal care. All women were systematically screened for both HCV and diabetes.

RESULTS—A total of 426 women were included in the sample. HCV infection was detected in 13 (3.1% [95% CI 1.7–5.0]) and type 2 diabetes in 22 (5.2%, [3.3–7.6]) women. Women diagnosed with type 2 diabetes were more obese and had higher serum alanine aminotransferase activity compared with women without diabetes. Four of 13 (30.8% [10.6–58.7]) HCV-infected women and 18 of 413 (4.4% [2.7–6.7]) women without evidence of HCV infection had type 2 diabetes. (odds ratio 9.8 [95% CI 2.4–34.0], Fisher’s exact test P = 0.003). In a logistic regression model, increasing age (10-year increments), obesity (by standard deviations from the mean BMI), and positive HCV status were each independently related to the diagnosis of diabetes.

CONCLUSIONS—Among American-Indian women, type 2 diabetes is more common in those with than in those without HCV infection. This association and its potential mechanisms may have clinical implications. Investigation into the mechanisms linking HCV infection to the expression of type 2 diabetes may also help to define processes that promote the development of type 2 diabetes in susceptible individuals.
Prevalence of the Metabolic Syndrome and Its Components
Authors: Ilanne-Parikka Pirjo , Eriksson Johan G. , Lindström Jaana , Hämäläinen Helena , Keinänen-Kiukaanniemi Sirkka , Laakso Mauri , Louheranta Anne , Mannelin Marjo , Rastas Merja , Salminen Virpi , Aunola Sirkka , Sundvall Jouko , Valle Timo , Lahtela Jorma , Uusitupa Matti , Tuomilehto Jaakko ,   the Finnish Diabetes Prevention Study Group
Published: March 2007

OBJECTIVE—To assess the prevalence of the metabolic syndrome (MetS) in two independent Finnish study cohorts.

RESEARCH DESIGN AND METHODS—The prevalence of the MetS by modified World Health Organization criteria was analyzed in different categories of glucose tolerance in a cross-sectional, population-based sample of 2,049 individuals (FINRISK) aged 45–64 years and in 522 participants of the Finnish Diabetes Prevention Study (DPS) with impaired glucose tolerance (IGT).

RESULTS—In the FINRISK cohort, the MetS was present in 38.8% of the men and 22.2% of the women. The prevalence was 14.4 and 10.1% in subjects with normal glucose tolerance, 74.0 and 52.2% in subjects with impaired fasting glucose, 84.8 and 65.4% in subjects with IGT, and 91.5 and 82.7% in subjects with type 2 diabetes in men and women, respectively. Among women, the prevalence of the MetS increased with increasing age. In the DPS cohort, the MetS was present in 78.4% of the men and 72.2% of the women with IGT.

CONCLUSIONS—The MetS was extremely common in middle-aged subjects The high prevalence in men was mostly due to their high waist-to-hip ratio. The prevalence of the MetS increased in both sexes with deterioration in glucose regulation. Approximately 75% of the subjects with IGT had the MetS. Because the syndrome includes the major risk factors for atherosclerotic vascular diseases and is the major antecedent for type 2 diabetes, concerted preventive action should be targeted to control all the features of the MetS.
Relationship of Depression and Diabetes Self-Care, Medication Adherence, and Preventive Care
Authors: Lin Elizabeth H.B. , Katon Wayne , Von Korff Michael , Rutter Carolyn , Simon Greg E. , Oliver Malia , Ciechanowski Paul , Ludman Evette J. , Bush Terry , Young Bessie
Published: March 2007

OBJECTIVE—We assessed whether diabetes self-care, medication adherence, and use of preventive services were associated with depressive illness.

RESEARCH DESIGN AND METHODS—In a large health maintenance organization, 4,463 patients with diabetes completed a questionnaire assessing self-care, diabetes monitoring, and depression. Automated diagnostic, laboratory, and pharmacy data were used to assess glycemic control, medication adherence, and preventive services.

RESULTS—This predominantly type 2 diabetic population had a mean HbA1c level of 7.8 ± 1.6%. Three-quarters of the patients received hypoglycemic agents (oral or insulin) and reported at least weekly self-monitoring of glucose and foot checks. The mean number of HbA1c tests was 2.2 ± 1.3 per year and was only slightly higher among patients with poorly controlled diabetes. Almost one-half (48.9%) had a BMI >30 kg/m2, and 47.8% of patients exercised once a week or less. Pharmacy refill data showed a 19.5% nonadherence rate to oral hypoglycemic medicines (mean 67.4 ± 74.1 days) in the prior year. Major depression was associated with less physical activity, unhealthy diet, and lower adherence to oral hypoglycemic, antihypertensive, and lipid-lowering medications. In contrast, preventive care of diabetes, including home-glucose tests, foot checks, screening for microalbuminuria, and retinopathy was similar among depressed and nondepressed patients.

CONCLUSIONS—In a primary care population, diabetes self-care was suboptimal across a continuum from home-based activities, such as healthy eating, exercise, and medication adherence, to use of preventive care. Major depression was mainly associated with patient-initiated behaviors that are difficult to maintain (e.g., exercise, diet, medication adherence) but not with preventive services for diabetes.
Oxidative Stress and Antioxidant Defense in Relation to the Severity of Diabetic Polyneuropathy and Cardiovascular Autonomic Neuropathy
Authors: Ziegler Dan , Sohr Christoph G.H. , Nourooz-Zadeh Jaffar
Published: March 2007

OBJECTIVE—Oxidative stress resulting from enhanced free-radical formation and/or a defect in antioxidant defenses has been implicated in the pathogenesis of experimental diabetic neuropathy. The objective of this study was to evaluate plasma levels of various biomarkers of oxidative stress in diabetic subjects in relation to the presence or absence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN).

RESEARCH DESIGN AND METHODS—Plasma 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide anion (O2·−) generation, lag phase to peroxidation by peroxynitrite (ONOO−), vitamin E-to-lipid ratio, and vitamin C were measured in nonsmoking diabetic patients without PN and CAN (PN−/CAN− group; n = 62), in a group with PN but without CAN (PN+/CAN− group; n = 105), in those with both PN and CAN (PN+/CAN+ group; n = 22), and in healthy control subjects (n = 85).

RESULTS—All three markers of oxidative stress were significantly increased, and both markers of antioxidant defense were decreased in the PN+/CAN− group compared with the control group (all P < 0.05). PN−/CAN− subjects showed a significant increase compared with control subjects for 8-iso-PGF2α, O2·−, and ONOO− and a decrease for the vitamin E-to-lipid ratio (all P < 0.05). In the PN+/CAN− group, a significant increase compared with the PN−/CAN− group was noted for O2·−, whereas the vitamin E-to-lipid ratio and vitamin C were reduced (all P < 0.05). No significant differences were noted between the PN+/CAN− and PN+/CAN+ groups for each of the five markers of oxidative stress. In multivariate models, O2·− and ONOO− were independently associated with neuropathic deficits, but diabetes duration and triglyceride levels were also independent determinants.

CONCLUSIONS—Oxidative stress is enhanced in diabetic patients before the development of PN but to an even higher degree in those with PN, without further significant increase in relation to superimposed autonomic neuropathy. However, apart from oxidative stress, diabetes duration and triglyceride levels are also related to the severity of PN.
Diabetes in Nonveterans, Veterans, and Veterans Receiving Department of Veterans Affairs Health Care
Authors: Reiber Gayle E. , Koepsell Thomas D. , Maynard Charles , Haas Linda B. , Boyko Edward J.
Published: March 2007

OBJECTIVE—To compare behavioral risk factors and health and disease characteristics among three groups of adults with diabetes: nonveterans, veterans not receiving Department of Veterans Affairs (VA) health care, and veterans using VA services.

RESEARCH DESIGN AND METHODS—Two data sources were used to describe the veteran population. First, the 2000 Behavioral Risk Factor Surveillance System (BRFSS) characterized the U.S. adult population by preventive health practices and risk behaviors linked to chronic and preventable diseases. New to the 2000 survey were questions on veteran status, which were administered in all states. Second, VA administrative and veterans benefits data were analyzed to describe comorbidity, education services, and veterans benefits.

RESULTS—The estimated prevalence of diabetes in male veterans receiving VA care was 16%. Male veterans with diabetes using VA care were more likely to be nonwhite, not employed, have lower income, lower health status, and more activity limitations than male veterans not using these services. Computerized records indicate VA users with diabetes also had high concurrent comorbidity. Frequency of VA diabetes and preventive care services, as measured by selected quality indicators, was equivalent to or higher than the levels reported by veterans not receiving VA care and nonveterans. In addition to health care, nearly one-fourth of veterans with diabetes also received monthly awards for compensation and pension.

CONCLUSIONS—Males receiving VA care with self-reported diabetes indicated receiving preventive care services at equivalent or higher levels than their counterparts receiving care outside the VA and nonveterans.
The Epidemiology of Lower-Extremity Disease in Veterans With Diabetes
Authors: Mayfield Jennifer A. , Reiber Gayle E. , Maynard Charles , Czerniecki Joseph , Sangeorzan Bruce
Published: March 2007

OBJECTIVE—To describe the epidemiology of lower-extremity complications of diabetes in veterans who are users of the Department of Veterans Affairs (VA).

RESEARCH DESIGN AND METHODS—Hospital discharge records for care provided in all VA hospitals in 1998 were obtained. All hospitalizations for lower-extremity ulceration, peripheral vascular procedures, and amputation were analyzed using frequency tables. A diabetes denominator was defined as a veteran with at least three ambulatory care visits with at least one diabetes diagnosis code. Age-specific and total age-adjusted rates of discharge with ulceration, vascular procedures, and amputation were calculated.

RESULTS—Veterans with diabetes comprised over half of all hospitalizations for lower-extremity ulceration, one-third of all hospitalizations for peripheral vascular procedures, and two-thirds of all hospitalizations for amputation. The age-specific discharge rate per 1,000 diabetic persons for age 0–64 years, 65–74 years, and 75 years and older for ulceration were 28.4, 31.0, and 37.9; for vascular procedures, the rates were 3.5, 4.4, and 4.4; and for amputation, the rates were 7.3, 9.0, and 10.0, respectively.

CONCLUSIONS—Veterans with diabetes comprise a significant proportion of hospitalizations for lower-extremity ulceration, peripheral vascular bypass, and amputation. Age-specific rates of diabetic amputation in veterans are lower than U.S. rates.
Eye Disease in Veterans With Diabetes
Authors: Orcutt James , Avakian Arpenik , Koepsell Thomas D. , Maynard Charles
Published: March 2007

OBJECTIVE—To describe the screening, prevalence, and management of eye disease in veterans cared for by the Veterans Affairs (VA) System.

RESEARCH DESIGN AND METHODS—Eye examinations, treatments, and diseases were identified in veterans with diabetes who received care in inpatient and outpatient VA settings during FY1998. Analysis was conducted to characterize the patient population and screened population and to compare them to the total VA patient population with diabetes. Logistic regression was performed to predict eye screening.

RESULTS—Overall 48% of veterans with diabetes had an eye examination in FY1998. One-third of all veterans had an eye condition and 8.6% of veterans had ophthalmic manifestations of diabetes. In addition 11% reported glaucoma and 17.8% reported cataract surgery. Approximately 11,500 (2.7%) veterans were blind.

CONCLUSIONS—Visual impairment is a common complication of diabetes. Half of this population of veterans had a visual examination recorded in VA. The VA is testing a more targeted screening and treatment approach for diabetic eye disease in order to prevent the serious eye complications.
Diabetes-Related Utilization and Costs for Inpatient and Outpatient Services in the Veterans Administration
Authors: Maciejewski Matthew L. , Maynard Charles
Published: March 2007

OBJECTIVE—The purpose of this study was to calculate the total number of inpatient hospitalizations, outpatient clinic visits, and total direct health care costs associated with veterans with diabetes receiving care in Veterans Administration (VA) facilities.

RESEARCH DESIGN AND METHODS—The number of inpatient hospitalizations is tracked for years 1994–1998, and outpatient clinic visits are tracked for years 1997 and 1998. Trends in utilization across different age and racial groups, as well as total direct inpatient and outpatient costs for 1998, are presented.

RESULTS—Between 1994 and 1998, hospitalization rates decreased from 1.68 to 1.61. The average number of outpatient visits was 4.5 in 1997 and 4.6 in 1998. VA incurred $214.8 million in outpatient expenditures and $1.45 billion in inpatient expenditures for veterans with diabetes receiving VA care.

CONCLUSIONS—Health care delivery systems and payors track the cost and utilization of services by specific patient groups to support disease management, quality improvement, external reporting, and cost containment. Tracking the utilization and cost of diabetes care is necessary to understand the financial impact of diabetes on health care systems and the overall burden of diabetes on individuals.
Validity and Reliability of an Instrument for Assessing Health-Related Quality of Life and Treatment Preferences
Authors: Peyrot Mark , Rubin Richard R.
Published: March 2007

OBJECTIVE—To provide a preliminary assessment of the validity and reliability of a new measure of health-related quality of life (HRQOL) and treatment preference for insulin delivery systems.

RESEARCH DESIGN AND METHODS—Study participants were 197 adults with type 1 or type 2 diabetes who completed the Insulin Delivery System Rating Questionnaire (IDSRQ), a self-administered questionnaire developed for this study. The IDSRQ assessed patient perceptions of treatment satisfaction, impact of treatment on daily activities, clinical efficacy, diabetes-related worries and social burdens, psychological well-being, and overall treatment system preference of patients using continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI).

RESULTS—The IDSRQ subscales had acceptable reliability (α = 0.67–0.92, median 0.82) and test-retest correlations (intraclass correlation coefficient 0.67–0.94, median 0.88). Floor effects (0–10%, median 0%) and ceiling effects (0–18%, median 4%) were minimal. There were statistically significant differences (P < 0.05) between patients using CSII and MDI on all IDSRQ subscales except psychological well-being (P = 0.096); differences in means were 0.3–1.4 SD units (median 0.9). Multiple regression analysis (controlling for age, sex, and type of diabetes) showed that treatment satisfaction, perceived clinical efficacy, and psychological well-being were independently associated with overall treatment preference and accounted for half of the difference in preference between CSII and MDI patients.

CONCLUSIONS—Preliminary findings suggest that the IDSRQ is a valid and reliable measure of HRQOL and treatment preferences for insulin delivery systems. The subscales are comprehensive, sensitive to differences in user populations, and account for most of the preference for a particular insulin delivery system.