title: Glucose metabolism in patients with schizophrenia treated with olanzapine or quetiapine: a frequently sampled intravenous glucose tolerance test and minimal model analysis.
abstract: OBJECTIVE
  Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism.
  
  
  METHODS
  A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls).
  
  
  RESULTS
  There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049).
  
  
  CONCLUSIONS
  Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results.
authors.affiliation: Schizophrenia Program, Massachusetts General Hospital, Boston, USA. dchenderson@partners.org
authors.forename: David C
authors.initials: DC
authors.lastname: Henderson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Copeland
authors.forename: Christina P
authors.initials: CP
authors.lastname: Borba
authors.forename: Tara B
authors.initials: TB
authors.lastname: Daley
authors.forename: Dana D
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Enrico
authors.initials: E
authors.lastname: Cagliero
authors.forename: A Eden
authors.initials: AE
authors.lastname: Evins
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Doug L
authors.initials: DL
authors.lastname: Hayden
authors.forename: Oliver
authors.initials: O
authors.lastname: Freudenreich
authors.forename: Corinne
authors.initials: C
authors.lastname: Cather
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D001835:Body Weight; D003430:Cross-Sectional Studies; D003987:Dibenzothiazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D015596:Nutrition Assessment; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D003987:Dibenzothiazepines; D007328:Insulin; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D005947:Glucose; D000077152:Olanzapine