INSULIN ACTION AND GLUCOSE-METABOLISM ARE IMPROVED BY GEMFIBROZIL TREATMENT IN HYPERTRIGLYCERIDEMIC PATIENTS

The aim of this study was to determine whether gemfibrozil-mediated de crease in very low density lipoprotein triglyceride (VLDL-TG) concentr ation is accompanied by an improvement in overall glucose metabolism i n hypertriglyceridemic patients. We assessed this hypothesis in 7 hype rtriglyceridemic without (HTG) and in 11 hypertriglyceridemic with non insulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-mon ths treatment either with the drug or with placebo. Placebo VLDL-TG co ncentrations in both HTG (3.82 +/- 0.92 mmol/l (mean +/- S.D.) vs. 3.9 1 +/- 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 gemfibr ozil 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 g roups, gemfibrozil treatment was associated with an improvement in fas ting 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 treatm ent 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 signific ant decrease in fasting free fatty acids (FFA) level was observed duri ng gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a signi ficant drop of these substrates was observed in both fasting and postp randial conditions, Insulin action estimated with the insulin toleranc e test (Kitt) was significantly higher after gemfibrozil treatment in both HTG (2.71 +/- 0.41 0%/min vs, 3.96 +/- 0.98 %/min, P = 0.016 vs. placebo), and in NIDDM-HTG (1.77 +/- 0.76 0%/min vs. 2.88 +/- 1.34 0%/ min, P = 0.016), Our data show that gemfibrozil treatment significantl y decreased VLDL-TG concentrations in both HTG and NIDDM-HTG and impro ved both fasting and postprandial glucose metabolism, These improved l ipid and glucose profiles appear to be secondary to a significant amel ioration in insulin action.