HLA gene and clinical study of insulin dependent diabetes mellitus (IDDM) in Chinese individuals.

The prevalence rate of diabetes in China was 0.67% in 1980. For the last ten years, the prevalence rate has increased 0.1% every year. The total number of diabetics in China is enormous, in the range of 12-15 million people; 10% have insulin dependent diabetes (IDDM) and 90% have non insulin dependent diabetes (NIDDM). 1) HLA Typing DR3 was statistically increased in Chinese IDDM patients; relative risk 7.89, Fisher's p 5.91 x 10-6 corrected p 4.14 x 10-6. DR3 is increased in most Caucasians and American Blacks, but not in Japanese individuals. 2) HLA-DQA1 and B1 alleles contribute to susceptibility to IDDM IDDM is strongly associated with the presence of arginine in position 52 of the DQ α chain and absence of aspartic acid in position 57 of the DQ β chain in Caucasians. To confirm this association in Chinese, extensive oligonucleotide dot blot hybridisation of PCR-amplified DQA1 and DQB1 genes were studied using samples from 48 IDDM patients and 46 healthy non diabetic control subjects. DQ α 52-Arg and DQ β 57-non-Asp are strongly associated with IDDM susceptibility as compared with controls (p < 0.001 and 0.006, respectively). DQ β 57-non-Asp homozygosity is associated with increased susceptibility to IDDM. DQ β 57-Asp homozygosity is associated with protection against IDDM; 14.6% of IDDM patients were homozygous for DQ β -Asp, compared with 0% of American patients; 22.9% of IDDM patients were homozygous for DQ β 57-nonAsp, compared with 96% of American diabetic subjects in a previous study. These results suggest that the effect of the DQ b 57-Asp variation on Chinese IDDM susceptibility is not as remarkable as in Caucasians, and there may be other alleles which contribute to IDDM susceptibility in Chinese individuals. 3) Familial Aggregation and HLA Typing of Pedigrees in IDDM In 280 cases with IDDM 1000 positive family histories of diabetes have been found to be present in 26.8% of IDDM probands. The prevalence of diabetes in relatives has been shown to be 68% in first degree relatives, 28% in second degree relatives and 4% in the third degree relatives. HLA data support the hypothesis that IDDM is a multigenic hereditary disorder. 4). Clinical Features of Microvascular Complications in Long Term IDDM One hundred sixty three individuals with IDDM of more than 10 years in duration were followed. Most complications were microvascular, such as proliferative retinopathy (39/163, 23.9%) and nephropathy (19/163, 11.7%). We have found that the development and degree of microvascular complications depend on the age of onset, diabetes duration and the long term glycaemic control. Especially, microvascular complications were found to be significantly influenced by glycaemic control in the first ten years after onset.