Objective: To measure insulin sensitivity and body composition in antipsychotic naïve patients with DSM IV schizophrenia and/or schizoaffective disorder compared with matched controls.

Design: Seven antipsychotic medication naïve patients fulfilling the DSM IV A criteria for schizophrenia /schizoaffective disorder were matched for body mass index (BMI), age and sex with seven control subjects. We measured endogenous glucose production and peripheral glucose disposal using a hyperinsulinemic euglycaemic clamp (plasma insulin concentration 200 pmol/l) in combination with stable isotopes. Fat content and fat distribution were determined with a standardized single-slice CT- scan and whole body DEXA scan.

Results: Endogenous glucose production during the clamp was 6.7 µmol/kg.min (SD 2.7) in patients versus 4.1 µmol/kg.min (SD 1.6) in controls, P = 0.02 (95% CI –5.2 – 0.006). Insulin-mediated peripheral glucose uptake was not different between patients and controls. The amount of subcutaneous abdominal fat in patients was 104.6 ± 28.6 cm³ and 63.7 ± 28.0 cm³ in controls, P = 0.04 (95% CI 4.4 – 77.2). Intra abdominal fat and total fat mass were not significantly different.

Conclusions: Antipsychotic medication naïve patients with schizophrenia or schizoaffective disorder display hepatic insulin resistance compared to matched controls. This finding cannot be attributed to differences in intra abdominal fat mass or other known factors associated with hepatic insulin resistance and suggests a direct link between schizophrenia and hepatic insulin resistance.