Effects of Gemfibrozil Therapy on Glucose Tolerance,Insulin Sensitivity and Plasma Plasminogen Activator Inhibitor Activity in Hypertriglyceridaemia

Abstract

Background Hypertriglyceridaemia (HTG), glucose intolerance, insulin resistance and elevated plasma activity of plasminogen activator inhibitor (PAI)-1 are risk factors for ischaemic heart disease. Because these conditions tend to cluster in the same individuals, the concerted action of gemfibrozil on all these parameters were investigated in a patient group with primary HTG.

Methods Gemfibrozil was given as 600 mg tablets twice a day for 12 months to a group of middle-aged non-diabetic men with moderate HTG. Patients served as their own controls, because the treatment period was preceded by a single-blinded 2-month placebo phase. Gradient gel electrophoresis subfractionation of HDL was performed and glucose tolerance was defined according to World Health Organization criteria. The insulin sensitivity was assessed by the insulin-modified minimal model method. Plasma PAI-1 was assayed as activity.

Results Serum triglyceride concentration was lowered by 49%. Serum high density lipoprotein (HDL) cholesterol concentration was raised by 11 % with percentage shift towards the smaller HDL_3c subfraction. The low-density lipoprotein cholesterol concentration remained unchanged. The proportion of glucose-intolerant subjects and insulin sensitivity were not altered by gemfibrozil. Plasma PAI-1 activity and fibrinogen levels were unaffected by gemfibrozil. The serum activity of γ-glutamyltranspeptidase was lowered in all patients.

Conclusion Gemfibrozil is safe and effective with regard to its serum triglyceride-lowering potential. However, glucose intolerance, insulin resistance and elevated plasma PAI-1 activity, frequently seen in HTG patients, are not to be expected to be normalized by this drug.