Atypical antipsychotics may “directly” influence glucose homeostasis, increasing risk of type 2 diabetes independently of changes in adiposity. Animal models suggest direct effects after even a single dose of certain atypical antipsychotics on glucose dysregulation. Here, we investigated effects of a single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby minimizing confounding effects of the illness of schizophrenia and adiposity. In a randomized double-blind crossover design, 15 subjects were administered 10 mg of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled intravenous glucose tolerance test was initiated 4.25 hours later to assess changes in glucose homeostasis, including an index of insulin sensitivity, disposition index, glucose effectiveness, and acute insulin response to glucose. We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs), insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C-reactive protein, interleukin 6, and tumor necrosis factor α). Complete data for both visits were analyzed for 12 subjects. Olanzapine treatment significantly decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25 hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may invoke early changes in some parameters of glucose and lipid metabolism, as well as endocrine indices.
From the *Center for Addiction and Mental Health; †Institute of Medical Sciences; ‡Department of Nutritional Sciences, University of Toronto; §Department of Medicine, St. Michael’s Hospital; ∥Department of Physiology; ¶Department of Psychology; #Department of Psychiatry, University of Toronto; **University Health Network; and ††Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Received August 3, 2012; accepted after revision March 6, 2013.
Reprints: Margaret Karolina Hahn, MD, PhD, FRCPC, Center for Addiction and Mental Health, 250 College St, Toronto, Ontario, Canada M5T 1R8 (e-mail: email@example.com; Margaret_Hahn@camh.net).
This work was funded through a grant from the Canadian Diabetes Association (Grant OG-3-08-2535-GR) to Gary J. Remington (PI).