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The time course of islet cell antibodies (ICA) and serum C-peptides responses (CPRs) to oral glucose tolerance tests (OGTTs) were studied prospectively up to 60 (mean 35) mo in 32 ICA-positive subjects [28 with non-insulin-dependent diabetes (NIDDM) and 4 subjects with impaired glucose tolerance (IGT); mean age 45 yr], 96 matched subjects [56 with NIDDM, 8 with IGT, and 32 normal first-degree relatives of patients with insulin-dependent diabetes (IDDM); mean age 45 yr] who were negative for ICA at the beginning of the study. In addition, the effects of human leukocyte antigens (HLA) on the time course of ICA and beta-cell function were evaluated. In 10 subjects (8 with NIDDM and 2 with IGT) who were ICA positive, ICA became undetectable, even by sensitive ICA assay, 15 +/- 2 mo (mean +/- SE) after initiation of this study. In these subjects, integrated serum CPR values (sigma CPR) and 2-h blood glucose values in response to OGTTs improved significantly (P less than .05-.01). In contrast, the remaining 22 subjects who were ICA positive were persistently positive for ICA. CPR and blood glucose responses deteriorated progressively in these 22 subjects, and 7 subjects in this group progressed to the insulin-dependent state. Serum CPR and blood glucose responses to OGTTs showed no remarkable changes in 64 patients (56 with NIDDM and 8 with IGT) and 32 normal first-degree relatives of patients with IDDM who remained negative for ICA throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

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