HLA typing and immunological characterization od young-onset diabetes mellitus in a Hong Kong Chinese population

Aims 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 phen otype suggestive of Type 2 diabetes mellitus, although up to 50% subsequent ly need insulin treatment. The aim of this study was to use a combination o f clinical, genetic and immunological markers to characterize the disease p henotype further in such individuals and to determine whether the requireme nt for insulin is the result of autoimmune disease. Methods One hundred and thirty-seven Hong Kong Chinese with young-onset dia betes were studied, irrespective of their mode of presentation. The subject s were typed for alleles of the HLA-DR and -DQ genes and investigated for t he presence of autoantibodies to glutamic acid decarboxylase (GAD). Plasma C-peptide concentration and requirement fur 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 gr oup, 35 patients (34.0%) were insulin-deficient, 16 (15.5%) were insulin-tr eated and seven (6.9%) were positive for GAD autoantibodies. Among the GAD- positive subjects presenting with Type 2 diabetes, the HLA-DRB1*03 allele m ay be a marker of early progression to insulin therapy. Conclusions Seven subjects with Type 2 diabetes at presentation had autoant ibodies to GAD. Causes other than GAD autoimmunity, however, must be sought to explain the high prevalence of insulin deficiency observed in the Chine se patients. This study highlights the heterogeneity of the pathogenic proc esses leading to the diabetic phenotype.