Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults

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Abstract
In a cross-sectional study, sera of 81 adult diabetic in-patients were tested for the presence of pancreatic islet cell antibodies (ICA), both IgG and complement-fixing. All patients had been well controlled initially with oral hypoglycaemic agents and therefore had been classified as having Type 2 (non-insulin-dependent) diabetes. However, 14 were subsequently classified as Type 1 (insulin-dependent) because they became insulin-dependent within 2 months of diagnosis. Ten of these patients (71%) were ICA-positive. Sixty-seven patients had been non-insulin-dependent for at least 1 year after diagnosis. Circulating ICA were present in 18 patients and 16 of these (89%) required insulin therapy. Secondary oral hypoglycaemic agent failure developed within a mean period of 3.7 years after diagnosis. In contrast, in the ICA-negative sub-group (n = 49) insulin treatment became necessary in 29 patients. Secondary oral hypoglycaemic agent failure of these patients had developed after a mean period of 8.4 years, which was significantly longer than in the ICA-positive patients (p< 0.01). Complement-fixing-ICA were detected only in sera with an ICA-IgG titre of at least 8, and its prevalence was similar in the sub-groups tested, i. e., the Type 1 diabetic patients and the patients with secondary oral hypoglycaemic agent failure. With HLA-DR typing, a significant excess of the DR3 antigen and heterozygous DR3/DR4 phenotypes was found in ICA-positive patients with secondary oral hypoglycaemic agent failure and in the Type 1 diabetic patients, which was comparable with the frequencies reported in juvenile-onset Type 1 diabetes. The heterozygous DR3/W6 phenotype was significantly increased in the ICA-positive patients when compared with 13 ICA-negative patients. Thus, the presence of ICA and an excess of certain HLA-DR phenotypes identify a sub-group within the adult diabetic population with secondary oral hypoglycaemic agent failure which can be regarded as a retarded form of Type 1 diabetes.