DECREASING TRIGLYCERIDE BY GEMFIBROZIL THERAPY DOES NOT AFFECT THE GLUCOREGULATORY OR ANTILIPOLYTIC EFFECT OF INSULIN IN NONDIABETIC SUBJECTS WITH MILD HYPERTRIGLYCERIDEMIA

We studied the effects of gemfibrozil on glucose and fatty acid metabo lism in subjects with mild endogenous hypertriglyceridemia. Twenty sub jects (serum triglycerides, 3.2 +/- 1.4 mmol/L; age, 52 +/- 7 years; b ody mass index, 27.8 +/- 1.8 kg/m(2)) were randomly allocated to recei ve either placebo or gemfibrozil 1,200 mg daily for 12 weeks in a doub le-blind study. Gemfibrozil decreased serum total and very-low-density lipoprotein (VLDL) triglycerides by 53% and 57%, respectively, and se rum apolipoprotein (ape) B concentration by 21%. Gemfibrozil had no ef fect on the diurnal concentration of free fatty acids (FFA). Neither d id gemfibrozil change diurnal blood glucose or serum insulin concentra tions. The endogenous glucose production rate remained unchanged in bo th groups during the treatment period, and was similarly suppressed by hyperinsulinemia. The rate of insulin-induced whole-body glucose disp osal increased similarly both before (basal 10.8 +/- 1.8, low dose ins ulin 10.5 +/- 2.1, and high-dose insulin 20.9 +/- 11.9 mu mol . kg(-1) . min(-1)) and after (11.1 +/- 1.7, 10.7 +/- 1.2, and 18.6 +/- 7.9, r espectively) gemfibrozil treatment. Rates of oxidative and nonoxidativ e glucose metabolism remained unchanged during gemfibrozil treatment. Basal pretreatment and posttreatment FFA turnover rates were similar i n both study groups, as were the rates of substrate oxidation. In summ ary, gemfibrozil proved to be an effective serum triglyceride-lowering agent in patients with mild hypertriglyceridemia, but had no effect o n the insulin sensitivity of glucose metabolism or of antilipolysis. T hese data support the idea that triglycerides per se do not cause insu lin resistance, and that the triglyceride-lowering effect of gemfibroz il is not mediated via antilipolytic action. Copyright (C) 1951 by W.B . Saunders Company