title: Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo.
abstract: The goal of this study was to evaluate the effect of olanzapine or risperidone treatment on beta-cell function in healthy volunteers. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d; n = 17), risperidone (4 mg/d; n = 13), or placebo (n = 18) for 15-17 d. Insulin secretion was quantitatively assessed at baseline and the end of the study period using the hyperglycemic clamp. Weight increased significantly (P < 0.01) in the olanzapine (2.8 +/- 1.7 kg) and risperidone (3.1 +/- 2.1 kg) treatment groups. An increase ( approximately 25%) in the insulin response to hyperglycemia and a decrease ( approximately 18%) in the insulin sensitivity index were observed after treatment with olanzapine and risperidone. The change in insulin response was correlated (r = 0.5576; P = 0.019) with a change in body mass index. When the impact of weight change was accounted for by multivariate regression analyses, no significant change in insulin response or insulin sensitivity was detected after treatment with olanzapine or risperidone. We found no evidence that treatment of healthy volunteers with olanzapine or risperidone decreased the insulin secretory response to a prolonged hyperglycemic challenge. The results of this study do not support the hypothesis that olanzapine or risperidone directly impair pancreatic beta-cell function.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Co., Corporate Center, Drop Code 1758, Indianapolis, IN 46285, USA. sowell_margaret_o@lilly.com
authors.forename: Margaret O
authors.initials: MO
authors.lastname: Sowell
authors.forename: Nitai
authors.initials: N
authors.lastname: Mukhopadhyay
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cavazzoni
authors.forename: Sudha
authors.initials: S
authors.lastname: Shankar
authors.forename: Helmut O
authors.initials: HO
authors.lastname: Steinberg
authors.forename: Alan
authors.initials: A
authors.lastname: Breier
authors.forename: Charles M
authors.initials: CM
authors.lastname: Beasley
authors.forename: Jamie
authors.initials: J
authors.lastname: Dananberg
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012016:Reference Values; D018967:Risperidone / Q000494:pharmacology*; D016037:Single-Blind Method; D015430:Weight Gain
chemical_list: D014150:Antipsychotic Agents; D007328:Insulin; D001569:Benzodiazepines; D010890:Pirenzepine; D018967:Risperidone; D000077152:Olanzapine