title: Weight and fat distribution in patients taking valproate: a valproate-discordant gender-matched twin and sibling pair study.
abstract: OBJECTIVE
  Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA-discordant same-sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed.
  
  
  METHODS
  Height, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%.
  
  
  RESULTS
  We studied 19 pairs of VPA-discordant, gender-matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within-pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA-user was treated for >11 years there were statistically significant mean within-pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%.
  
  
  CONCLUSIONS
  This study demonstrated a relationship between long-term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA.
authors.affiliation: Department of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia; Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia; Ormond College, Parkville, Victoria, Australia.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Petty
authors.forename: Susan
authors.initials: S
authors.lastname: Kantor
authors.forename: Kate M
authors.initials: KM
authors.lastname: Lawrence
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Marnie
authors.initials: M
authors.lastname: Collins
authors.forename: Keith D
authors.initials: KD
authors.lastname: Hill
authors.forename: Joanna
authors.initials: J
authors.lastname: Makovey
authors.forename: Philip N
authors.initials: PN
authors.lastname: Sambrook
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: John D
authors.initials: JD
authors.lastname: Wark
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects; D015502:Absorptiometry, Photon; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D050218:Body Fat Distribution; D004200:Diseases in Twins / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D012737:Sex Factors; D035781:Siblings; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D020738:Leptin; D014635:Valproic Acid
keywords: Antiepileptic medication; Comorbidities of epilepsy; Medication side effects; Obesity