Elevated levels of insulin, leptin, and blood lipids in olanzapine-treatedpatients with schizophrenia or related psychoses

Background: The aim of this study was to investigate the influence of the a ntipsychotic agent olanzapine on glucose-insulin homeostasis to explain pos sible mechanisms behind olanzapine-associated weight gain. Method: Fourteen patients on treatment with olanzapine tall meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting bloo d samples for glucose, insulin, the growth hormone (GH)-dependent insulin-l ike growth factor I, and the insulin-dependent insulin-like growth factor b inding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. M oreover, weight change during olanzapine treatment was determined. Results: Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were n ot available for the other 2 patients. Eight patients (57%) had BMI above t he normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin leve ls (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjec ts. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hy pertriglyceridemia, and 85%(11/13) hypercholesterolemia. Weight change corr elated positively to blood glucose levels and inversely to the serum concen tration level of N-desmethylolanzapine. Additionally, the levels of blood g lucose, triglycerides, and cholesterol correlated inversely to the serum co ncentration of N-desmethylolanzapine. Conclusion: Olanzapine treatment was associated with weight gain and elevat ed levels of insulin, leptin, and blood lipids as well as insulin resistanc e, with 3 patients diagnosed to have diabetes mellitus. Both increased insu lin secretion and hyprleptinemia may be mechanisms behind olanzapine-induce d weight gain. Moreover, it is suggested that the metabolite N-desmethylola nzapine, but not olanzapine, has a normalizing effect on the metabolic abno rmalities.