Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia

Abstract

To examine whether lowering of plasma triglyceride concentrations using the fibrate peroxisome proliferator-activated receptor (PPAR)alpha agonist gemfibrozil would influence insulin sensitivity to various aspects of intermediary metabolism among subjects with type 2 diabetes mellitus. A randomized placebo-controlled double-blind study in 12 subjects with type 2 diabetes were treated for 12 weeks after a 12-week dietary run-in. Insulin sensitivity was assessed using a low-dose incremental intravenous insulin infusion. Gemfibrozil significantly reduced fasting serum triglyceride concentrations (p < 0.001) but had no effect on measures of diabetic control. Neither gemfibrozil nor placebo treatment altered insulin sensitivity of glucose or glycerol metabolism during low-dose insulin infusion, but significant falls in both non-esterified fatty acid (NEFA) (p = 0.003) and ketone concentrations (p = 0.002) were observed after treatment with gemfibrozil. Gemfibrozil does not affect insulin sensitivity to glucose or fat metabolism in type 2 diabetes but enhances the lowering of plasma NEFA concentrations by insulin, probably by reducing hepatic fatty acid synthesis.