Impaired Insulin-Stimulated Glucose Oxidation and Free Fatty Acid Suppression in Patients with Familial Combined Hyperlipidemia

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Abstract
Abstract —Familial combined hyperlipidemia (FCHL) is characterized by hyperlipidemia and insulin resistance, but intracellular defect in insulin action is unknown. Therefore, we investigated insulin action by applying the hyperinsulinemic euglycemic clamp technique with indirect calorimetry in 58 FCHL family members (28 with FCHL; 30 without dyslipidemia; aged 49±12 years; body mass index [BMI], 25.2±4.0 kg/m 2 ) and in 72 healthy control subjects (aged 54±6 years; BMI, 26.3±3.1 kg/m 2 ). In the fasting state, FCHL patients had higher levels of total cholesterol, total triglycerides, and apolipoprotein B than control subjects ( P P =0.001) and higher rates of lipid oxidation (0.15±0.13 versus 0.01±0.25 mg/kg/min; P =0.024), as well as higher levels of serum-free fatty acids (FFA) (0.24±0.17 versus 0.06±0.06 mmol/L; P P P =0.408). In FCHL family members without dyslipidemia and in control subjects, FFAs during the clamp correlated positively with levels of total triglycerides ( P P =0.008). We conclude that in patients with FCHL, and also in their first-degree relatives, insulin’s suppressive effect on FFA levels is impaired, which may precede dyslipidemia in FCHL.

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