A family study of the association between insulin dependent diabetes mellitus, autoantibodies and the HLA system

Abstract

A family study of the patients attending a pediatric diabetic clinic was undertaken. Seventy-three percent of the index patients and their families provided samples for HLA typing and autoantibody analysis. The HLA types were analyzed and correlated with the autoantibody data. Ways of predicting which siblings are at risk of developing insulin dependent diabetes mellitus (IDDM) were sought. The antigen DR4 carries a higher relative risk and .delta. value (viz. 27 and 0.93) than any other antigen. The data did not support the notion of heterogeneity of IDDM on the basis of HLA types or autoantibody status. However, the majority of patients with a younger age of onset were DR4/DR4 homozygotes. The presence of ICA [islet cell autoantibodies] was a good marker for siblings at risk of developing IDDM. Some siblings who developed IDDM had ICA and CF-ICA [complement fixing ICA] for long periods of time before developing diabetes. The data supported an intermediate model of inheritance for IDDM.