HLA typing and immunological characterization of young-onset diabetes mellitus in a Hong Kong Chinese population.
OBJECTIVE
A study of the Hong Kong Chinese showed that the majority of subjects with young-onset diabetes (age of diagnosis < 35 years) present with a phenotype suggestive of Type 2 diabetes mellitus, although up to 50% subsequently need insulin treatment. The aim of this study was to use a combination of clinical, genetic and immunological markers to characterize the disease phenotype further in such individuals and to determine whether the requirement for insulin is the result of autoimmune disease.


METHODS
One hundred and thirty-seven Hong Kong Chinese with young-onset diabetes were studied, irrespective of their mode of presentation. The subjects were typed for alleles of the HLA-DR and -DQ genes and investigated for the presence of autoantibodies to glutamic acid decarboxylase (GAD). Plasma C-peptide concentration and requirement for insulin were also determined.


RESULTS
One hundred and three subjects presented with a syndrome resembling Type 2 diabetes, while 34 presented with Type 1 diabetes. Of the former group, 35 patients (34.0%) were insulin-deficient, 16 (15.5%) were insulin-treated and seven (6.9%) were positive for GAD autoantibodies. Among the GAD-positive subjects presenting with Type 2 diabetes, the HLA-DRB1*03 allele may be a marker of early progression to insulin therapy.


CONCLUSIONS
Seven subjects with Type 2 diabetes at presentation had autoantibodies to GAD. Causes other than GAD autoimmunity, however, must be sought to explain the high prevalence of insulin deficiency observed in the Chinese patients. This study highlights the heterogeneity of the pathogenic processes leading to the diabetic phenotype.
Kelly
M A
MA
Department of Medicine, University of Birmingham, UK. m.a.kelly@bham.ac.uk
Chan
J C
JC
Heward
J
J
Mijovic
C H
CH
Zimmet
P Z
PZ
Yeung
V T
VT
Cockram
C
C
Barnett
A H
AH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People; D001323:Autoantibodies / Q000097:blood; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002681:China / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005006:Ethnicity; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006723:Hong Kong; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D001323:Autoantibodies; D002096:C-Peptide; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D005968:Glutamate Decarboxylase