Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism.
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.
van Nimwegen
Lonneke J M
LJ
Department of Psychiatry, Adolescent Clinic, Laboratory of Endocrinology and Radiochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
Storosum
Jitschak G
JG
Blumer
Regje M E
RM
Allick
Gideon
G
Venema
Henk W
HW
de Haan
Lieuwe
L
Becker
Hiske
H
van Amelsvoort
Therese
T
Ackermans
Mariette T
MT
Fliers
Eric
E
Serlie
Mireille J M
MJ
Sauerwein
Hans P
HP
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
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine