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 antipsychoticnaive patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls. Design: 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 similar to 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 mu mol/kg.min (SD 2.7) in patients vs. 4.1 mu mol/kg.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.