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The disease association of autoantibodies to proinsulin and insulin was compared in patients with Type 1 (insulin-dependent) diabetes mellitus and first-degree relatives. Following the recommendation of the Fourth International Workshop on the Standardization of insulin autoantibodies, autoantibodies were determined by fluid-phase radioimmunoassay using equimolar concentrations of mono-125I-A14-insulin or -proinsulin to detect insulin or proinsulin autoantibodies, respectively. A higher prevalence of proinsulin autoantibodies vs insulin autoantibodies was found in 97 patients with Type 1 diabetes prior to insulin treatment (34.0% vs 22.7%, p less than 0.05) and in 16 islet cell antibody-positive relatives (43.8% vs 31.3%, NS). There was only one serum positive for insulin and proinsulin autoantibodies in 110 islet cell antibody-negative first degree relatives (0.9%). None of 88 normal sera contained proinsulin autoantibodies or insulin autoantibodies. There was a close correlation of proinsulin autoantibody and insulin autoantibody titres in individual sera (r = 0.95, p less than 0.01) due to crossreaction of all insulin autoantibodies with proinsulin. However, some proinsulin autoantibodies did not crossreact with insulin. Background binding in normal sera was lower for proinsulin autoantibodies. We conclude that proinsulin autoantibodies have a higher association to acute Type 1 diabetes than insulin autoantibodies.

Proinsulin autoantibodies are more closely associated with Type 1 (insulin-dependent) diabetes mellitus than insulin autoantibodies