Role of islet autoimmunity in the aetiology of different clinical subtypesof diabetes mellitus in young north Indians

Aims To determine the role of islet autoimmunity in the aetiology of differ ent clinical subtypes of diabetes mellitus in young north Indian patients b y measuring islet autoantibodies. Methods In a cross-sectional study, 145 young patients with diabetes (onset < 30 years) were subdivided into the following categories: Type 1 diabetes (n = 83), malnutrition-modulated diabetes mellitus (MMDM, n = 31) and fibr o-calculous pancreatic diabetes (FCPD, n = 31). MMDM subjects presented wit h emaciation and severe insulin-requiring but ketosis-resistant diabetes, w hile FCPD was associated with idiopathic chronic calcific pancreatitis. Ant ibodies to glutamic acid decarboxylase (GADA) and IA-2 (IA-2 A) were detect ed by immunoprecipitation of S-35-labelled recombinant antigens and cytopla smic islet cell antibody (ICA) by indirect immunofluorescence. Results GADA were present in a significant proportion (23%) of patients wit h MMDM. In contrast, IA-2 A was increased only among patients with Type 1 d iabetes (22%), but not MMDM (3%, P < 0.05). Among patients with a duration of diabetes < 2 years, GADA and/or IA-2 A were found in 61% of Type 1 diabe tic and 37% of MMDM patients (P < 0.01). MMDM patients who were positive fo r GADA had a shorter duration of diabetes, but did not differ in their age at onset of diabetes, body mass index, fasting plasma C-peptide, or frequen cy of thyroid microsomal and parietal cell antibodies. FCPD subjects had th e lowest prevalence of autoantibodies: IA-2 and ICA were absent, while GADA were present in 7% (P < 0.05 vs. Type 1 diabetes). Conclusions GADA, though not IA-2 A, were present in a substantial proporti on of patients with the MMDM variant of diabetes, suggesting that islet aut oimmunity map play a role in its pathogenesis. In contrast, none of the isl et antibodies was increased in subjects with FCPD, making it likely that it is a secondary type of diabetes.