Etiology of early-onset type 2 diabetes in Indians: islet autoimmunity and mutations in hepatocyte nuclear factor 1alpha and mitochondrial gene.
BACKGROUND
Indians are at high risk of developing type 2 diabetes mellitus (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
The objective was to delineate the clinical features in young Indian patients with T2DM and to determine the role of mutations in the hepatocyte nuclear factor 1alpha (HNF1alpha) gene [MODY3 (maturity-onset diabetes of the young, type 3)], mitochondrial A3243G mutation, and islet autoimmunity in its etiology.


METHODS
This was an observational cohort study.


METHODS
The setting was an outpatient diabetes clinic in a teaching hospital.


METHODS
Ninety-six consecutive young patients with T2DM (onset, <or=30 yr) were included in the study.


METHODS
Glutamic acid decarboxylase and insulinoma antigen 2 antibodies, mitochondrial A3243G mutation, and the common HNF1alpha mutation P291fsinsC were measured in all patients. The entire HNF1alpha gene was studied for mutations in 32 subjects with onset less than 25 yr or with normal weight. The common HNF1alpha A98V polymorphism was studied in 91 patients.


RESULTS
The patients were clinically heterogeneous, with 42% having a normal body mass index. Glutamic acid decarboxylase antibodies were present in three (3%) subjects and mitochondrial A3243G mutation in one (1%) subject. The P291fsinsC mutation was not detected in any patient. A MODY3 mutation (R200W) was detected in one patient (3%). In this family, diabetes cosegregated with the R200W mutation in the proband and his youngest brother but not in three 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 HNF1alpha gene mutations were infrequent.
Sahu
Ravi P
RP
Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India.
Aggarwal
Ajay
A
Zaidi
Ghazala
G
Shah
Ajay
A
Modi
Kirti
K
Kongara
Srikanth
S
Aggarwal
Suraksha
S
Talwar
Sudha
S
Chu
Su
S
Bhatia
Vijayalakshmi
V
Bhatia
Eesh
E
D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000276:immunology; D005192:Family Health; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics*; D005838:Genotype; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007194:India; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic
D001323:Autoantibodies; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha