Altering Triglyceride Concentrations Changes Insulin-Glucose Relationships in Hypertriglyceridemic Patients: Double-Blind Study With Gemfibrozil With Implications for Atherosclerosis

OBJECTIVE: To determine whether reducing triglyceride concentrations in humans reduces serum insulin levels and consider the implications of this for the insulin resistance of hypertriglyceridemia. RESEARCH DESIGN AND METHODS: Insulin and glucose levels were determined during an oral glucose tolerance test (OGTT) in 14 volunteers who had a range of basal triglyceride levels. A double-blind crossover design was used to study active and placebo gemfibrozil and relate triglyceride changes to insulin and glucose levels. Diet and weight were kept constant. RESULTS: Glucose concentrations during OGTT were the same in both treatment periods. Insulin concentrations were reduced in proportion to reductions in triglyceride. CONCLUSIONS: Triglyceride reduction in hypertriglyceridemic patients is associated with a decrease in serum insulin. This does not appear to be a direct effect of gemfibrozil, because it does not occur without a sufficient fall in triglyceride levels. Because glucose concentration remains the same despite the reduced insulin, the triglyceride reduction may result in greater sensitivity to insulin. Treatment of hypertriglyceridemia may break a vicious and potentially atherogenic cycle of hypertriglyceridemia and hyperinsulinemia.