Summary
Hypertriglyceridaemia and insulin resistance are closely associated but it is unknown whether hypertriglyceridaemia per se contributes to insulin resistance. In the present study we examined whether gemfibrozil, by lowering triglyceride levels, improves the glucoregulatory and antilipolytic action of insulin in Type 2 (non-insulin-dependent) diabetes mellitus. Twenty patients were randomly allocated to receive either placebo or gemfibrozil 1200 mg daily for 12 weeks in a double-blind study. Very low density lipoprotein triglyceride levels decreased in the gemfibrozil group by 42±12% (p<0.01). Gemfibrozil had no effect on the diurnal concentration of non-esterified fatty acids (NEFA). At the randomization HbA1c levels were comparable (7.6±0.3 vs 7.8±0.2%, NS) and increased slightly both in the gemfibrozil (8.2±0.4%, p<0.05) and placebo groups (8.0±0.3%, NS). Pre- and post-treatment diurnal glucose and insulin concentrations remained unchanged. Basal pre- and post-treatment hepatic glucose production rates were comparable in both groups and similarly suppressed by insulin. Rate of whole body glucose disposal during a low-dose insulin infusion (serum insulin ∼90 pmol/l) (pre- vs post-gemfibrozil 11.9±1.1 vs 11.1±0.7, pre- vs post-placebo 9.9±1.1 vs 10.8±0.8 μmol·kg−1·min−1, NS for both) and a high-dose insulin infusion (serum insulin ∼500 pmol/l) (16.2+-1.7 vs 17.7±2.7, 17.1±4.2 vs 17.4±2.9 μmol·kg−1·min−1, respectively, NS for both) remained unchanged. Basal pre- and post-treatment NEFA turnover rates were comparable in both groups and similarly suppressed by insulin. Also rates of total lipid oxidation, plasma NEFA oxidation and non-oxidative NEFA metabolism remained unchanged in both groups. We conclude that gemfibrozil effectively lowers serum triglycerides but has no effect on insulin sensitivity of glucose and NEFA metabolism. The data suggest that hypertriglyceridaemia is a consequence rather than a cause of insulin resistance in Type 2 diabetic patients.
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Vuorinen-Markkola, H., Yki-Järvinen, H. & Taskinen, M.R. Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in Type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 161–169 (1993). https://doi.org/10.1007/BF00400699
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DOI: https://doi.org/10.1007/BF00400699