Abstracts

Rationale: Valproic acid (VPA) is an extensively used broad-spectrum antiepileptic drug. One of the most common side effects of the treatment with VPA is weight gain which occurs in about half of the patients and is associated with important metabolic and endocrine abnormalities. VPA treatment has been reported to be associated with high fasting serum insulin concentrations, insulin resistance in parallel with an unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in woman. Nevertheless, there are no studies that explored the prevalence of metabolic syndrome (MS) in patients treated with VPA, compared to the general population. The aim of our study was to compare the prevalence of MS and its components in VPA-treated patients to the general population. Methods: 75 adult patients (40 male and 35 female) from Southern Estonia receiving VPA monotherapy for at least 3 months were included in this study. These participants were interviewed, clinically examined, and blood samples for VPA, fasting plasma glucose, serum insulin, C-peptide concentrations were taken after an overnight fast. The homeostasis model assessment (HOMA) index was calculated. MS was diagnosed according to Adult Treatment Panel III criteria. Data was compared to the results of a population-based cross-sectional multicentric study on the prevalence of metabolic disorders (n=495) conducted in Southern Estonia two years earlier. Results: The occurence of MS in VPA-treated patients was not increased comparing to the general population IR=0.99 (95% CI 0.52-1.63). The weighted prevalence of MS in Estonian population was 25.9%. The body mass index (BMI) also did not significantly differed between both groups: 26.6±5.7 in VPA-treated patients, 28.2±6.2 in controls. Nevertheless, the VPA-treated patients had significantly lower fasting plasma glucose concentrations 5.09±0.56 mmol/l (p=0.002) and higher fasting serum insulin levels 10.10±8.30 mU/l (p<0.0001) comparing to the controls: 5.43±0,82 mmol/l and 6.34±5.5 mU/l, respectively. In addition, the HOMA index (p=0,004) was higher in patients than in control subjects. Interestingly, the normal-weight VPA-treated patients (BMI<25kg/m2) had also higher serum insulin (p<0.0001) concentrations than the normal-weight control subjects. HOMA index was also higher (p<0.0001) in the VPA-treated normal-weight patients than in normal-weight controls. Conclusions: Metabolic syndrome is not more common in VPA-treated adult epilepsy patients than in the general population. However, VPA-treated patients have lower serum glucose, higher insulin concentration in the peripherial circulation and increased insulin resistance independently of the presence of obesity.