Please select the eligibility criteria that correspond to the clinical trial below.
Title: Subcutaneous Insulin Glargine Versus NPH Insulin in Patients With Chronic Kidney Disease Stages III and IV: Randomized Controlled Trial.
Brief Summary: Chronic kidney disease (CKD) is one of the most common microvascular complications of diabetes mellitus, and it is the leading cause of end stage renal disease on developed countries. The CKD diagnosis and its progression require re-evaluation of hypoglycemic therapy and constant dosing adjustments, in order to optimize glycemic control and minimize its side effects. Long acting insulin analogs and its pharmacokinetics have not been studied through different stages of kidney disease and there is no consensus defining the appropriate dosing adjustment based on the glomerular filtration rate (GFR). This research project will compare the glycemic response to intensive insulin treatment with NPH insulin and basal insulin analog (insulin glargine) in type 2 diabetes (DM 2) patients with CKD stages 3 and 4. Patients and methods - Inclusion Criteria: DM 2 patients with CKD secondary to diabetic nephropathy and GFR of 15-59 ml/min/1.73m². Exclusion Criteria: Patients with systemic neoplasia, HIV, CKD or nephropathy from other etiologies, severe psychiatric disorders and pregnant women. Study design: This study consists of a randomized, cross-over, open-label controlled clinical trial. Patients will be randomly divided into two groups: GROUP 1 - insulin analog glargine once a day and GROUP 2 - NPH human insulin, three applications per day, both group will be treated with insulin lispro at mealtime. The laboratory tests will be performed at baseline and 12, 24, 36 and 48 weeks after the study start. During routine medical appointments will be analyzed self- monitoring of capillary blood glucose (SMBG) and the hypoglycemia score. After 24 weeks the basal insulin will be changed, i.e. patients using NPH insulin will receive insulin glargine and patients on insulin glargine will be changed to NPH insulin. A CGMS will be carried out at 24 and 48 weeks. Methodology: The metabolic profile will be evaluated throughout SMBG; biochemical, hormonal and hematological measurements; hypoglycemia score and CGMS. Statistical analysis will be performed using comparative descriptive analyzes, such as chi-square distribution, t-test and non-parametric tests. Analyze of data CGMS will include the area under the curve and the related statistic. Finally, logistic regression models will be adopted to evaluate the effect of the treatment on the several variables in question.


Options:
A: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
* Female or male, 18 years≤age≤70years
* Subjects with insulin naïve type 2 diabetes who have been treated with metformin（\>1g/d）alone for at least 3 months prior to screening
* 11%≥HbA1c≥7.5% based on analysis from a central laboratory
* 24kg/m2≤BMI≤40kg/m2
* Weight fluctuation\<2kg in one month prior to screening
* Able and willing to perform self-monitoring of blood glucose.
* Willing to accept basal insulin therapy
* Able to self-inject all required doses of insulin

Exclusion Criteria:

* Treatment with any OADs (Oral Antidiabetic Drugs) in the last 6 months, except metformin (subjects currently treated with metformin within the interval of 1000-2000 mg daily may be included in the trial. The dose should have remained unchanged for a period of one month prior to randomisation and should be expected to remain unchanged throughout the trial period).
* Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramine, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, NSAIDs, tricyclic anti-depressants, atypical anti-psychotics).
* Participation in a clinical study of weight control within the last 3 months prior to screening.
* Previous or planned surgical treatment of obesity.
* Any disease or condition (such as renal, hepatic or cardiac) according to the judgment of the Investigator makes the subject unsuitable for participation in the trial.
* Anticipated change in concomitant medication known to interfere with glucose metabolism, such as systemic steroids, non-selective beta-blockers or mono amine oxidase (MAO) inhibitors.
* Anticipated change in concomitant medication known to interfere with lipid metabolism, such as lipid-lowering drugs.
* Proliferative retinopathy or maculopathy that has required acute treatment within the last six months.
* Uncontrolled hypertension (treated or untreated) as judged by the Investigator
* Known or suspected allergy to trial product(s) or related products.
* Previous participation in this trial. Participation is defined as screened.
* Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or consistent use of barrier methods.
* Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
* Any condition that the Investigator feels would interfere with trial participation or evaluation of results.
* Receipt of any investigational drug (NPH or insulin detemir) within 1 month prior to this trial.
* Cardiac disease defined according to NYHA class III or IV, unstable angina pectoris and/or myocardial infarction within the last 6 months previous to the selection.
* History of hypoglycaemic unawareness.
* With mental implant (such as cardiac pacemaker, insulin pump) in vivo.
B: Inclusion Criteria:

* Type 2 diabetic suboptimally controlled on their previous antidiabetic treatment

  * 18 ≤ age ≤ 75
  * Stable dose of oral antidiabetic treatment for \> 8 weeks
  * The number of OADs that the patients used should be "3" or less
  * HbA1c level \> 7.0% and \< 10%
  * Fasting plasma glucose \> 8mmol/L and \<15mmol
  * BMI \< 40 kg/m2
  * Patient who is capable and willing to perform regular SMBG
  * Patient who is capable and willing for insulin injection
  * Confirmed written consent
  * Insulin naïve

Exclusion Criteria:

* Participation in a clinical trial with any investigational drug used with curative intent and within 30 days prior to study entry
* Patient known to have hypoglycaemia unawareness or recurrent major hypoglycaemia
* Any product containing prandial insulin
* Concomitant medication known to interface with glucose metabolism (such as systematic steroids)
* Change in dose of non-insulin anti-diabetic treatment or initiation of new anti-diabetic medications in the last 8 weeks prior to screening
* Patients treated with steroid or nonsteroidal anti-inflammatory drugs
* Patient who had experienced an acute concurrent illness during the 3-month period before the investigation
* Patient with hepatic disease and end-stage renal disease
* Patients unable to comply with follow-up visits
* Pregnant or breastfeeding women
C: Inclusion Criteria:

* Type 2 diabetes
* Insulin naive
* Treatment with oral anti-diabetic drugs (OADs) for at least 3 months and not achieving therapeutic targets
* HbA1c between 8% - 10.5%

Exclusion Criteria:

* Secondary diabetes, MODY (Maturity Onset Diabetes of the Young)
* Previous treatment with insulin (except for short-term treatment with insulin for intercurrent illness as judged by the Investigator)
* Proliferative retinopathy, maculopathy requiring treatment,
* Hypoglycaemia unawareness as judged by the Investigator, recurrent major hypoglycaemia
* End stage liver disease (increased liver enzymes 4 fold), end stage renal disease assessed by MDRD (Modification of Diet in Renal Disease) less than 30 ml/min or dialysed patient, acute heart failure, any acute cardiovascular event or cerebrovascular event less than 6 months
* Acute disease with poor prognosis
* History of alcoholism, drug abuse, or psychiatric disease or personality disorders likely to invalidate voluntary consent or to prevent good compliance with the trial protocol
* Mental incapacity, unwillingness or language barrier precluding adequate understanding or co-operation (patients having a score of less than 15 in a previous MMSE (Mini-Mental State Examination) in the last six months) and any conditions as judged by the investigator
* Legal incapacity or limited legal capacity (patients under guardianship or curatorship)
* Concomitant medication for Alzheimers treatment (Memantine, Anticholinesterasique treatment)
* Participation in another clinical trial less than one month before inclusion in this trial
* Illness requiring repeated hospitalisation
* Known or suspected allergy to the insulin or any compositional component
* Anticipated change or new use in concomitant medication known to interfere with glucose metabolism, such as systemic corticotherapy more than 5 mg/day (prednisone)
* Any other condition that the Investigator feels would interfere with trial participation or evaluation of results
* Terminal illness
D: Inclusion Criteria:

* Patients with type 2 diabetes mellitus and chronic kidney disease secondary to diabetic nephropathy in stages 3 and 4 (moderate and severe nephropathy, corresponding to glomerular filtration rate of 15-59 ml/min/1.73m²) will be included in the study.

Exclusion Criteria:

* Patients with systemic neoplasias,
* HIV, chronic kidney disease or nephropathy from other etiologies,
* severe psychiatric disorders
* pregnant women.

Answer: D