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Effects of gemfibrozil therapy on glucose tolerance, insulin sensitivity and plasma plasminogen activator inhibitor
1King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden.
Insights
Gemfibrozil effectively lowers triglycerides in patients with hypertriglyceridaemia (HTG). However, it does not improve glucose intolerance, insulin resistance, or plasminogen activator inhibitor-1 (PAI-1) activity associated with HTG.
Area of Science:
- Cardiology
- Endocrinology
- Metabolic Syndrome
Background:
- Hypertriglyceridaemia (HTG) is linked to increased risk of ischaemic heart disease.
- Associated risk factors include glucose intolerance, insulin resistance, and elevated plasminogen activator inhibitor-1 (PAI-1) activity.
- These metabolic abnormalities often coexist in individuals with HTG.
Purpose of the Study:
- To investigate the effects of gemfibrozil on multiple cardiovascular risk factors in patients with primary HTG.
- To assess gemfibrozil's impact on serum lipids, glucose metabolism, insulin sensitivity, and PAI-1 activity.
Main Methods:
- A 12-month randomized, placebo-controlled trial involving middle-aged men with moderate HTG.
- Gemfibrozil (600 mg twice daily) was administered after a 2-month placebo phase.
- Measurements included serum lipids (triglycerides, HDL, LDL), glucose tolerance (WHO criteria), insulin sensitivity (minimal model method), and plasma PAI-1 activity.
Main Results:
- Gemfibrozil significantly reduced serum triglyceride levels by 49%.
- HDL cholesterol increased by 11%, with a shift towards the HDL3c subfraction; LDL cholesterol remained unchanged.
- No significant alterations were observed in glucose intolerance, insulin sensitivity, or plasma PAI-1 activity. Gamma-glutamyltranspeptidase activity decreased.
Conclusions:
- Gemfibrozil demonstrates significant efficacy in lowering serum triglycerides in patients with HTG.
- The drug does not normalize glucose intolerance, insulin resistance, or elevated PAI-1 activity often observed in HTG patients.
- Gemfibrozil is considered safe and effective for triglyceride reduction, but not for addressing associated metabolic dysfunctions.
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 HDL3c 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 gamma-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.