Acute Insulin Response and β-Cell Compensation in Normal Subjects Treated With Olanzapine or Risperidone for 2 Weeks
- Thomas A. Hardy, MD, PHD1,
- Adam L. Meyers, MS1,
- Jun Yu, MS2,
- Sudha S. Shankar, MD3,
- Helmut O. Steinberg, MD3 and
- Niels K. Porksen, MD, PHD1
- 1Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana
- 2MedFocus Ltd., Des Plaines, Illinois
- 3Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana
- Address correspondence and reprint requests to Thomas A. Hardy, MD, PhD, Eli Lilly and Company, Lilly Corporate Center, DC 2138, Indianapolis, IN 46285. E-mail: hardyta{at}lilly.com
- AIR, acute insulin response
- AUC, area under the curve
- DI, disposition index
- HOMA1-IR, homeostasis model assessment-1 of insulin resistance
- ISI, insulin sensitivity index
A recent report by Ader et al. (1) suggested that olanzapine, an atypical antipsychotic, impaired β-cell compensation for insulin resistance in dogs. Such a mechanism could contribute to the important, but poorly understood, increase in diabetes risk among antipsychotic users. We previously reported that olanzapine and risperidone did not impair insulin secretory response based on a prospective study (2) of normal subjects using steady-state measurements during a hyperglycemic clamp. Here, we report additional data from this study focusing on the acute insulin response (AIR), allowing a comparison with the results of Ader et al. (1) by calculating a disposition index (DI) as a measure of β-cell compensation (3). Our hypothesis was that olanzapine treatment did not significantly change the DI derived from indexes of AIR and insulin sensitivity.
RESEARCH DESIGN AND METHODS—
A detailed description of this study has been reported previously (2). Briefly, lean (mean BMI ∼24 kg/m2) healthy volunteers were randomized to treatment with placebo (n = 18), olanzapine (10 mg/day; n = 17), or risperidone (4 mg/day; n = 13). Subjects were treated with half-maximal doses for 4 days before dose escalation. Subjects underwent hyperglycemic clamps (4) before randomization and after 15–17 days of treatment. Hyperglycemia was initiated with an intravenous priming dose of 20% (wt/vol) glucose estimated to produce a target level of glycemia (11.1 mmol/l). Half of the priming dose was …
