To examine the relationship between non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM), we studied beta-cell function, HLA type, and serologic markers of IDDM and NIDDM in the parents of IDDM patients. Fifty-two parents of 33 IDDM patients were examined in terms of islet-cell antibody (ICA) status, haptoglobin phenotype, HLA type, and insulin responses during an oral glucose tolerance test (OGTT). Twenty-seven parents were prospectively evaluated for up to 113 months. They were divided into the following three groups based on pattern of ICA positivity during the follow-up period: group 1, persistently positive ICA (n = 4); group 2, fluctuating ICA (n = 7); and group 3, persistently negative ICA (n = 16). Twenty-three percent (12 of 52) of the parents of IDDM patients had NIDDM, and 12% (six of 52) of the matched controls did. The prevalence of ICA in the parents (11 of 52, 21%) was greater than in normal controls (one of 112, P < .01). Diabetic parents tended to show a higher prevalence of ICA (six of 12, 50%) than nondiabetic parents (six of 40, 15%; P = .06). ICA-positive parents showed higher glucose levels and lower insulin responses than ICA-negative parents. Three of four parents in group 1 slowly progressed to an insulin-dependent state during 25 +/- 3 months of follow-up evaluation. Parents in group 2 and group 3 did not show any changes in glucose levels or insulin responses during the study.(ABSTRACT TRUNCATED AT 250 WORDS)