Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients Original Research Article

The aim of this study was to determine whether gemfibrozil-mediated decrease in very low density lipoprotein triglyceride (VLDL-TG) concentration is accompanied by an improvement in overall glucose metabolism in hypertriglyceridemic patients. We assessed this hypothesis in 7 hypertriglyceridemic without (HTG) and in 11 hypertriglyceridemic with noninsulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-months treatment either with the drug or with placebo. Placebo VLDL-TG concentrations in both HTG (3.82 ± 0.92 mmol/l (mean ± S.D.) vs. 3.91 ± 1.01 mmol/l) and in NIDDM-HTG (6.62 ± 3.93 mmol/l vs. 6.84 ± 4.16 mmol/l) were not different from baseline values, whereas gemfibrozil decreased VLDL-TG in both groups (1.84 ± 0.56 mmol/l, P < 0.001 for HTG, and 1.93 ± 2.68 mmol/l, P = 0.013 in NIDDM-HTG). In both groups, gemfibrozil treatment was associated with an improvement in fasting plasma glucose levels (from 5.85 ± 0.92 mmol/l to 4.87 ± 0.40 mmol/l in HTG, P = 0.001, and from 11.47 ± 2.92 mmol/l to 9.56 ± 3.41 mmol/l in NIDDM-HTG, P = 0.042). In NIDDM-HTG, gemfibrozil treatment was associated with a significantly lower 2 h-postprandial plasma glucose level (9.87 ± 3.63 vs. 13.09 ± 3.62, P = 0.05). A significant decrease in fasting free fatty acids (FFA) level was observed during gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a significant drop of these substrates was observed in both fasting and postprandial conditions. Insulin action estimated with the insulin tolerance test (Kitt) was significantly higher after gemfibrozil treatment in both HTG (2.71 ± 0.41 %/min vs. 3.96 ± 0.98 %/min, P = 0.016 vs. placebo), and in NIDDM-HTG (1.77 ± 0.76 %/min vs. 2.88 ± 1.34 %/min, P = 0.016). Our data show that gemfibrozil treatment significantly decreased VLDL-TG concentrations in both HTG and NIDDM-HTG and improved both fasting and postprandial glucose metabolism. These improved lipid and glucose profiles appear to be secondary to a significant amelioration in insulin action.