Insulin-related metabolic changes during treatment with valproate in patients with epilepsy.

Weight gain is a known side effect of valproate (VPA) therapy, which is associated with hyperinsulinemia and polycystic ovary-like syndrome and unfavorable lipid changes in women. Hyperinsulinemia has also been observed in male and lean subjects as well. Hyperinsulinemia is associated with several health risks, such as cardiovascular diseases and the metabolic syndrome. The purpose of this study was to evaluate whether VPA-related hyperinsulinemia is associated with other metabolic changes and whether there is any association between weight gain, other adverse effects related to VPA, and the metabolic syndrome. Fifty-one patients under VPA monotherapy and 45 healthy control subjects participated in the study. They were interviewed and clinically examined, and, after an overnight fast, blood samples were taken to evaluate fasting serum insulin, lipid, free fatty acid, and uric acid levels. Incidence of the metabolic syndrome was determined as well. Compared with control subjects, VPA-treated patients had higher circulating insulin concentrations relative to body mass index, higher uric acid and triglyceride levels, and lower high-density lipoprotein cholesterol concentrations. There was no significant difference in the frequency of the metabolic syndrome between the VPA-treated patient group and the control group. In conclusion, valproate therapy, especially if started at a young age, is associated with increased circulating insulin concentrations relative to body mass index, indicating that the high insulin levels are not a consequence of obesity. Although the frequency of the metabolic syndrome did not differ between VPA-treated patients and control subjects, VPA-treated patients had higher concentrations of triglycerides and uric acid and lower levels of high-density lipoprotein cholesterol than control subjects.