Context: Indians are at high risk of developing type 2 diabetes (T2DM) at an early age, despite their lower body mass index. Studies on the etiology of patients presenting as early-onset T2DM in this racial group are not available.

Objective: To delineate the clinical features in young Indian patients with T2DM and to determine the role of mutations in the HNF 1 gene (MODY3), mitochondrial A3243G mutation and islet autoimmunity in its etiology.

Design: Observational cohort study

Setting: Out-patient diabetes clinic in a teaching hospital

Patients: 96 consecutive young patients with T2DM (onset 30 years)

Interventions: GAD and IA2 antibodies, mitochondrial A3243G mutation and the common HNF1 mutation P291fsinsC were measured in all patients. The entire HNF-1 gene was studied for mutations in 32 subjects with onset <25 years or with normal weight. The common HNF-1 A98V polymorphism was studied in 91 patients.

Results: The patients were clinically heterogeneous with 42% having a normal body mass index. GAD antibodies were present in 3 (3%) subjects and mitochondrial A3243G mutation in 1 (1%) subject. The P291fsinsC mutation was not detected in any patient. A MODY3 mutation (R200W) was detected in 1 patient (3%). In this family, diabetes co-segregated with the R200W mutation in the proband and his youngest brother but not in 3 paternal uncles. The Val 98 allele was associated with T2DM (allele frequency 0.14 vs. 0.03 in controls, odds ratio 5.2, p<0.001)

Conclusions: Despite a significant proportion of young Indian patients with T2DM having normal weight, islet autoimmunity, A3243G mitochondrial and HNF1 gene mutations were infrequent.