Plasma glucose and insulin responses to oral glucose and mixed meals and the ability of insulin to stimulate glucose disposal were quantified in normal volunteer subjects and patients with types IIA, IIB, and IV hyperlipoproteinemia (HLP). The results indicated that patients with either type IIB or IV HLP had higher plasma glucose (p < 0.05-< 0.001) and insulin (p < 0.001) responses to both oral glucose and mixed meals compared with the normal subjects and patients with type IIA HLP. Steady-state plasma glucose concentrations (mmol/L) were also higher (p < 0.001) in patients with types IIB (13.3 +/- 0.6) and IV (12.8 +/- 1.2) HLP during a continuous infusion of somatostatin, glucose, and insulin than either the control group (volunteer subjects) (6.2 +/- 0.9) or patients with type IIA HLP (5.6 +/- 1.0). Because the steady-state plasma insulin concentrations were similar in all four groups, patients with either type IIB or IV HLP were resistant to insulin-mediated glucose uptake. These data indicate that patients with hypertriglyceridemia are insulin resistant, glucose intolerant, and hyperinsulinemic, irrespective of the plasma cholesterol concentration. The results further demonstrate that hypercholesterolemic patients with normal triglyceride concentrations do not have any abnormalities of glucose and insulin metabolism.