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

• Change in HbA1c, blood glucose, pro-insulin, insulin and C-Peptide (F/ PP) at end of 6 and 12 weeks [ Time Frame: At 6 and 12 weeks ] [ Designated as safety issue: Yes ]
• Change in body weight, serum lipids at 18 weeks [ Time Frame: At 18 weeks ] [ Designated as safety issue: Yes ]
• Assessment of safety profile of sitagliptin [ Time Frame: At 6 ,12 and 18 weeks ] [ Designated as safety issue: Yes ]

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.

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

• Drug: Metformin
  less than 1 gram per day
• Drug: Placebo
  less than 1 gram per day
• Behavioral: Lifestyle Modification
  Lifestyle modification

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