title: Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism.
abstract: OBJECTIVE
  Our objective was to measure insulin sensitivity and body composition in antipsychotic-naive patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls.
  
  
  METHODS
  Seven antipsychotic medication-naive patients fulfilling the DSM IV A criteria for schizophrenia/schizoaffective disorder were matched for body mass index, age, and sex with seven control subjects. We measured endogenous glucose production and peripheral glucose disposal using a hyperinsulinemic euglycemic clamp (plasma insulin concentration approximately 200 pmol/liter) in combination with stable isotopes. Fat content and fat distribution were determined with a standardized single-slice computed tomography scan and whole body dual-energy x-ray absorptiometry.
  
  
  RESULTS
  Endogenous glucose production during the clamp was 6.7 micromol/kg x min (sd 2.7) in patients vs. 4.1 micromol/kg x min (sd 1.6) in controls (P = 0.02) (95% confidence interval -5.2 to 0.006). Insulin-mediated peripheral glucose uptake was not different between patients and controls. The amount of sc abdominal fat in patients was 104.6 +/- 28.6 cm(3) and 63.7 +/- 28.0 cm(3) in controls (P = 0.04) (95% confidence interval 4.4-77.2). Intraabdominal fat and total fat mass were not significantly different.
  
  
  CONCLUSIONS
  Antipsychotic medication-naive patients with schizophrenia or schizoaffective disorder display hepatic insulin resistance compared with matched controls. This finding cannot be attributed to differences in intraabdominal fat mass or other known factors associated with hepatic insulin resistance and suggests a direct link between schizophrenia and hepatic insulin resistance.
authors.affiliation: Department of Psychiatry, Adolescent Clinic, Laboratory of Endocrinology and Radiochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Lonneke J M
authors.initials: LJ
authors.lastname: van Nimwegen
authors.forename: Jitschak G
authors.initials: JG
authors.lastname: Storosum
authors.forename: Regje M E
authors.initials: RM
authors.lastname: Blumer
authors.forename: Gideon
authors.initials: G
authors.lastname: Allick
authors.forename: Henk W
authors.initials: HW
authors.lastname: Venema
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.forename: Hiske
authors.initials: H
authors.lastname: Becker
authors.forename: Therese
authors.initials: T
authors.lastname: van Amelsvoort
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.forename: Mireille J M
authors.initials: MJ
authors.lastname: Serlie
authors.forename: Hans P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine