Recent studies have suggested that the family history of non-insulin-dependent diabetes mellitus (NIDDM) influences glucose metabolism in subjects with normal glucose tolerance (NGT). However, it is not known whether the family history of NIDDM influences glucose metabolism in impaired glucose tolerance (IGT). We studied in a well-characterized group the impact of family history of NIDDM (diabetes mellitus [DM]-positive) in subjects with IGT on glucose disposal rate (GDR) measured by the euglycemic hyperinsulinemic clamp technique combined with indirect calorimetry. We recruited subjects from our previous population-based studies, and verified their glucose tolerance status twice during the follow-up period of 1 year. Subjects with NGT (n = 10) and IGT (n = 18) were comparable with respect to age, sex distribution, body mass index, smoking habits, and hypertension. As a group, IGT subjects showed lower GDR than the NGT group (28.6 +/- 12.1 v 38.9 +/- 13.6 mumol/kg/min, P < .05). IGT DM-positive subjects showed a 40% lower GDR than the NGT group (P < .05) and a 29% lower GDR than IGT DM-negative subjects (P = NS). IGT DM-positive subjects had lower glucose oxidation (P = NS, P < .01), glucose nonoxidation (P = NS, P = .01), and suppression of lipid oxidation (P = NS, P < .05) during the hyperinsulinemic euglycemic clamp as compared with IGT DM-negative and NGT groups, respectively. In conclusion, in subjects with persistent IGT, the family history of NIDDM is associated with the reduced total whole-body, oxidative, and nonoxidative GDR.