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

A family study of the patients attending a paediatric 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 analysed and correlated with the auto-antibody 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 was a good marker for siblings at risk of developing IDDM. Some siblings who developed IDDM had ICA and CF-ICA for long periods of time before developing diabetes. The data supported an intermediate model of inheritance for IDDM.