Phenotypic and Genetic Correlates of Diabetes (Non-Type 1) in Young Non-Obese Asian Indians in North India and A Study to Evaluate the Efficacy of Sitagliptin (DPP-4 Inhibitor) in a Sub-group of the Study Population

Study Overview
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Brief Summary
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This is a phase IV study of 3.5 years duration to evaluate the phenotypic and genetic correlates of diabetes (non-Type 1 in young non-obese Asian Indians in North India and pilot case control study to evaluate the efficacy of sitagliptin (DPP-4 inhibitor) in a sub-group of the study population.

Detailed Description
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A phase IV on T2DM with BMI < 25 kg/m2 and age 14-40 years. Primary Objectives: To investigate phenotype (body composition, anthropometry, pancreatic imaging and endocrine function, insulin resistance, autoantibodies, and other biochemical variables) and genetic (known mutations and polymorphisms) correlates in young (age 14-40 years) diabetic patients (non-type 1). Secondary Objectives: To study anthropometric and body fat distribution including truncal fat, subcutaneous and intra-abdominal fat in non-obese young patients with diabetes (non-type 1). To study whether insulin secretion, insulin resistance or a combination of both is/are the predominant defect(s) in non-obese young diabetics (non-type 1). To study the prevalence of autoimmunity and/or specific genetic abnormalities in this subgroup of diabetics. To estimate approximate prevalence of diagnostic subcategories based on the sample of population, and profile of complications in each category. To propose rational use of specialized investigations (e.g. GAD65, HNF-1α mutations etc) while investigating a newly diagnosed young diabetic. To determine the rational therapeutic option and prognosis in this sub-population of diabetics based on anthropometric, biochemical, and etiological profiles. Sample size: 205 patients to be enrolled and 120 patients to be enrolled for sub group study

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Metformin
* Behavioral: Lifestyle modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Young (18 to 40 years) patients with diabetes (not on insulin therapy) during the past 6 months and having BMI <25 kg/m2. Drug naïve patients Patients on mono-therapy with metformin (< 1g/day). Exclusion Criteria: Type 1 diabetes Type 2 Diabetes on any other oral hypoglycemic agent other than metformin Pregnancy or lactation Insulin or Sulfonylurea treatment within the past 3 months Has received any investigational drug with the past 60 days History of prior allergy or hypersensitivity to any drug (unless approved by investigator) HbA1c < 7.5% or > 8.5%. Unstable glycemic control, requiring addition of 2nd oral agent/insulin or frequent up-titration of dose of metformin. Any patient on insulin. Females of child bearing potential who are not using adequate contraception during the study period. Insulin dependent or history of ketoacidosis requiring hospitalization Acute infections Advanced end-organ damage (CLD, CRF etc.) Diabetes with clinically significant or advanced end-organ damage

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>1 gm metformin per day | Drug: Metformin<br> <br> |
| Other: control<br>lifestyle intervention | Behavioral: Lifestyle modification<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c |  | 18 weeks | 
| HbA1C |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety profile of sitagliptin |  | 18 weeks | 
| insulin |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maturity onset diabetes of the young 3 protein, human