title: Evaluate the effects of long-term valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients: A prospective study.
abstract: OBJECTIVE
  Excessive weight gain associated with sodium valproate (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. We prospectively evaluated the long-term impact of VPA monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. Our primary objective is to understand the underlying mechanism responsible for VPA-induced obesity.
  
  
  METHODS
  Sixty-six female patients with newly diagnosed or untreated epilepsy were included in the study. Thirty-four patients with VPA and thirty-two patients with LTG were treated for a period of one year in our center. Anthropometric and clinical data were collected at 5 time points: before, at 6th week, 3rd month, 6th month, 9th month and 12th month (last visit). Biochemical and hormonal data were collected 2 time points: before and last visit.
  
  
  RESULTS
  Subjects in the VPA group had significantly higher body weight than LTG-treated subjects (64.88±3.25 vs. 58.28±2.43, P<0.001). HOMA-IR level was significantly increased (2.76 vs. 1.35, P<0.05), and adiponectin levels were significantly lower in the VPA group (3.46 vs. 6.22, P<0.05). Triglycerides levels were significantly increased (118 vs. 96, P<0.05), and HDL-C levels were significantly lower in the VPA group. Both the VPA-treated group and the LTG-treated group showed no significant difference in term of total cholesterol, LDL-C, fasting blood glucose and serum leptin levels.
  
  
  CONCLUSIONS
  Based on the findings of this study, we proposed that VPA induced hypoadiponectinemia which correlates significantly with insulin resistance. These two factors may be responsible for weight gain, possible by stimulating appetite. Valproic acid appears to be use cautionally in obese females with epilepsy.
authors.affiliation: Department of Pharmacology, M.M. University, Mullana, Ambala, Haryana 133207, India. Electronic address: drharry5000@hotmail.com.
authors.forename: Harpreet Singh
authors.initials: HS
authors.lastname: Sidhu
authors.affiliation: Department of Neurology, M.S. Ramaiah Memorial Hospital, Bangalore 560054, India. Electronic address: drsrinivasa@yahoo.co.in.
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
authors.affiliation: Department of Pharmacology, M.M. University, Mullana, Ambala, Haryana 133207, India. Electronic address: akshaysadhotra@gmail.com.
authors.forename: Akshay
authors.initials: A
authors.lastname: Sadhotra
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000172:deficiency; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D000077213:Lamotrigine; D008661:Metabolism, Inborn Errors / Q000139:chemically induced; D011446:Prospective Studies; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
chemical_list: D052242:Adiponectin; D000927:Anticonvulsants; D001786:Blood Glucose; D008076:Cholesterol, HDL; D014227:Triazines; D014280:Triglycerides; D014635:Valproic Acid; D002784:Cholesterol; D000077213:Lamotrigine
keywords: Adiponectin; Body mass index; Insulin resistance; Lamotrigine; Sodium valproate