Abstract

The purpose of this study was to elucidate the background of valproate-related weight gain and hyperinsulinaemia both in men and women by studying markers of insulin resistance and metabolic syndrome. In addition, the role of leptin, a messenger between adipose tissue and the central nervous system was studied.

Valproate has a broad spectrum of antiepileptic activity and is widely used for the treatment of epilepsy. It has been the drug of choice for generalised epilepsy, such as juvenile myoclonic epilepsy, and it is also effective for treatment of partial seizures. In addition, valproate is used to treat other diseases, such as bipolar psychiatric disorders and migraine.

The results show that valproate-treated patients have higher serum insulin levels in relation to body mass index than control subjects. This indicates that the high serum insulin levels are not a consequence of increased body mass, especially, as the body mass index did not differ between the VPA treated patients and the control groups. Valproate therapy started at a young age may more often result in elevated serum insulin levels and associated other untoward metabolic changes. Furthermore, according to the present data, high serum insulin levels are a consequence of compromised metabolism of insulin in the liver, rather than reflecting reduced insulin sensitivity. However, the valproate-treated patients cluster risk factors for cardiovascular diseases, although the occurrence of metabolic syndrome is not more common in valproate-treated patients than in control subjects. Leptin does not play an independent role in valproate-related weight gain.