Effects of physiological plasma insulin levels on glucose turnover parameters in familial hypercholesterolemia

Eight young, non-obese patients with primary familial hypercholesterolemia (FH) and 8 healthy subjects matched for age, body mass index, lean body mass, plasma triglyceride and HDL-levels and arterial blood pressure were selected from a lipid clinic. Patients with FH had higher plasma LDL-cholesterol (8.3 +/- 0.5 vs. 4.1 +/- 0.2 mmol/l, P < 0.001) than controls but similar plasma triglyceride (1.15 +/- 0.04 vs. 1.10 +/- 0.02 mmol/l P = NS) levels. Both study groups were submitted to a euglycaemic hyperinsulinemic glucose clamp combined with simultaneous infusion of [3H]glucose to measure insulin action on whole-body glucose uptake and on hepatic glucose production. Two insulin infusion rates (0.15 mU/kg per min from 0 to 120 min and 0.30 mU/kg per min from 121 to 240 min) were used resulting in similar plasma insulin levels in both groups studied. Our results demonstrate that both whole-body glucose uptake and hepatic glucose output are similar in the fasting state as well as during insulin administration in both groups of subjects. We conclude that, in the absence of other causes of insulin resistance, isolated hypercholesterolemia is associated with normal sensitivity to insulin in both liver and peripheral tissues.