Background and objectives: Weight gain is an adverse metabolic effect in some children with epilepsy. The studies done to detect the effect of antiepileptic drugs and weight homeostatic hormones, insulin and leptin, were limited and controversial.

Materials and methods: We evaluated the serum leptin and insulin as predictors of weight gain in children receiving long-term treatment with valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG). This study included 90 patients (treated: 70; untreated: 20). Serum lipid profile, insulin and leptin were measured.

Results: BMI, serum leptin and insulin were significantly elevated in VPA compared with controls, untreated patients and those treated with CBZ, LTG and combined therapy with LTG. Girls on VPA had higher BMI and leptin levels than boys. With VPA, serum insulin was correlated with BMI (r=0.625, p<0.01), leptin (r=0.823, p<0.001), treatment duration (r=0.775, p<0.01) and VPA dose (r=0.975, p<0.0001). Serum leptin was correlated with age (r=0.980, p<0.0001), BMI (r=0.704, p<0.01), serum insulin (r=0.823, p<0.001), LDL-c (r=0.630, p<0.01), HDL-c (r=-0.880, p<0.001), treatment duration (r=0.770, p<0.01) and VPA dose (r=0.970, p<0.001). BMI is correlated with serum insulin, leptin, LDL-c (r=0.835, p<0.001) and HDL-c (r=-0.955, p<0.0001).

Conclusion: Hyperinsulinemia and hyperleptinemia are common with VPA and marked among epileptic children who gained weight suggesting states of insulin and leptin resistances. These alterations were not demonstrated with CBZ or LTG. The relationship between VPA, leptin and weight seems to be gender specific. Serum leptin may serve as a sensitive parameter for weight gain and reduction with intervention programs during follow-up of girls with epilepsy.