title: Serum insulin and leptin levels in valproate-associated obesity.
abstract: OBJECTIVE
  Weight gain is an important adverse effect of valproate (VPA) therapy, and it is associated with hyperinsulinemia and hyperandrogenism in women with epilepsy. Leptin is considered a signaling factor regulating body weight and energy metabolism. In human subjects, obesity is in general associated with elevated serum leptin levels, suggesting decreased sensitivity to leptin. The present study aimed at evaluating the role of insulin and leptin in VPA-related obesity.
  
  
  METHODS
  Body mass index (BMI) was calculated, and serum insulin and leptin levels were measured in 81 patients with epilepsy taking VPA and in 51 healthy control subjects.
  
  
  RESULTS
  Forty (49%) of the patients taking VPA and 25 (49%) of the control subjects were obese. The mean insulin levels were higher in VPA-treated patients than in the control subjects despite similar BMI values, when all subjects were included in the comparison. Both obese male and female patients taking VPA had higher serum insulin levels than the respective control subjects with similar BMI values. Serum insulin levels also were higher in lean male and lean female patients compared with the lean control subjects of same sex. Serum leptin levels did not differ between the VPA-treated patients and the control subjects.
  
  
  CONCLUSIONS
  Both obese and lean patients taking VPA for epilepsy have hyperinsulinemia, suggesting development of insulin resistance. This may be one of the factors leading to weight gain during VPA treatment. However, the results of the present study do not suggest an independent role for leptin in the pathogenesis of VPA-related obesity.
authors.affiliation: Department of Neurology, University of Oulu, Oulu, Finland. virpi.plyvanen@oulu.fi
authors.forename: Virpi
authors.initials: V
authors.lastname: Pylvänen
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Arto
authors.initials: A
authors.lastname: Pakarinen
authors.forename: Mervi
authors.initials: M
authors.lastname: Kotila
authors.forename: Jukka
authors.initials: J
authors.lastname: Turkka
authors.forename: Jouko I T
authors.initials: JI
authors.lastname: Isojärvi
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood* / Q000502:physiology; D008297:Male; D009765:Obesity / Q000097:blood* / Q000139:chemically induced* / Q000503:physiopathology; D012737:Sex Factors; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D007328:Insulin; D020738:Leptin; D014635:Valproic Acid