Genetic and immunologic factors in microvascular disease in type I insulin-dependent diabetes.

A detailed study of 133 subjects with insulin-dependent (type I) diabetes with severe microvascular disease has failed to substantiate the hypothesis that HLA factors influence the predisposition to this type of complication. A significant association between proliferative retinopathy and raised levels of circulating immune complexes was found. The distribution of insulin-binding levels in serum was similar to that in patients without complications. There was no correlation between insulin binding and the presence of immune complexes and no evidence was found that these complexes contained anti-insulin, anti-nuclear, or organ-specific antibodies. The distribution of insulin-binding levels in these subjects with diabetes of long duration was similar to that observed in 270 subjects with juvenile-onset short-duration type I diabetes. When the data were combined, significant associations between HLA-B8 and low/absent insulin binding levels were observed. HLA-BW62 was not associated with either high or low insulin-binding capacity. It is concluded that HLA genetic factors, insulin-binding capacity, and autoimmunity are unrelated to the pathogenesis of microvascular disease. Raised levels of circulating immune complexes may well be secondary to widespread tissue damage in diabetes of long duration.