Role of islet autoimmunity in the aetiology of different clinical subtypes of diabetes mellitus in young north Indians.
OBJECTIVE
To determine the role of islet autoimmunity in the aetiology of different clinical subtypes of diabetes mellitus in young north Indian patients by 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 fibro-calculous pancreatic diabetes (FCPD, n = 31). MMDM subjects presented with emaciation and severe insulin-requiring but ketosis-resistant diabetes, while FCPD was associated with idiopathic chronic calcific pancreatitis. Antibodies to glutamic acid decarboxylase (GADA) and IA-2 (IA-2 A) were detected by immunoprecipitation of 35S-labelled recombinant antigens and cytoplasmic islet cell antibody (ICA) by indirect immunofluorescence.


RESULTS
GADA were present in a significant proportion (23%) of patients with MMDM. In contrast, IA-2 A was increased only among patients with Type 1 diabetes (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 diabetic and 37% of MMDM patients (P < 0.01). MMDM patients who were positive for 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 frequency of thyroid microsomal and parietal cell antibodies. FCPD subjects had the 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 proportion of patients with the MMDM variant of diabetes, suggesting that islet autoimmunity may play a role in its pathogenesis. In contrast, none of the islet antibodies was increased in subjects with FCPD, making it likely that it is a secondary type of diabetes.
Singh
A K
AK
Department of Endocrinology, Sanjay Gandhi Postgraduate Institute, Lucknow, India.
Bhatia
E
E
Dabadghao
P
P
Bhatia
V
V
Gellert
S A
SA
Colman
P G
PG
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D002114:Calcinosis / Q000150:complications / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007194:India / Q000453:epidemiology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D009748:Nutrition Disorders / Q000150:complications / Q000453:epidemiology; D010195:Pancreatitis / Q000150:complications / Q000453:epidemiology
D001323:Autoantibodies; D002096:C-Peptide; C024211:islet cell antibody; D005968:Glutamate Decarboxylase