Insulin resistance in epileptic girls who gain weight after therapy with valproic acid.

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 +/- 25.3 versus 28.2 +/- 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid.