The presence of insulin resistance in 20 male nondiabetic patients with familial combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index (BMI) was investigated using the minimal model method modified by the administration of insulin and an oral glucose tolerance test. The peripheral sensitivity of insulin, expressed as the insulin sensitivity index (Si), was 1.91+/-1.05 and 2.86+/-1.19 x 10(-4) x min(-1) x mU/L in FCH patients and controls, respectively (P < .01), and the corresponding value for the peripheral utilization of glucose independently of insulin (Sg) was 1.70+/-1.13 in FCH patients and 2.35+/-0.60 x 10(-2) x min(-1) in controls (P < .02). In the FCH group, the Si value correlated significantly (P < .05) with the waist to hip ratio (WHR), plasma triglycerides (TG), free fatty acids (FFA), and the area under the curve of glucose (AUCg) and insulin (AUCi). In the control group, the correlation also reached statistical significance (P < .05) with age, BMI, WHR, blood pressure, TG, AUCg, and AUCi. Subgrouping the subjects with respect to central obesity defined as a WHR of 0.95 or greater, we observed lower Si values in obese and non-obese FCH subjects relative to controls (P < .02). The mean Si value in obese subjects was significantly lower than in non-obese FCH subgroups (1.40+/-0.79 v 2.68+/-0.95 x 10(-4) x min(-1) x mU/L, respectively, P < .01). In conclusion, a higher degree of insulin resistance relative to control values appears to be an integral part of the metabolic derangements observed in FCH, and central-trunk obesity exacerbates the insulin resistance syndrome.