Islet cell autoimmunity in youth onset diabetes mellitus in Northern India


      We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5±6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD65 and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. Five types of diabetes were delineated: Type 1 (37%), ketosis resistant (32%), Type 2 (13%), fibrocalculous pancreatopathy (11%) and autoimmune polyglandular syndrome (7%). C-peptide response to glucagon was assessed in a representative subset of 50 patients with Type 1, ketosis resistant, and autoimmune polyglandular syndrome. A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD65 plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. However, GAD65 antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. The fibrocalculous pancreatopathy group showed GAD65 plus IA-2 autoantibody positivity in 14.2% and GAD65 autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. Type 1 showed significantly less C-peptide response to glucagon when compared to the ketosis resistant and autoimmune polyglandular syndrome groups. The controls and Type 2 diabetic individuals tested negative for islet cell autoimmunity markers. These findings demonstrate a role of islet cell autoimmunity in the pathogenesis of four out of the five clinical types of youth onset diabetes seen in North India.


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