Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.
OBJECTIVE
Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown.


METHODS
We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test.


RESULTS
At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance.


CONCLUSIONS
This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.
Ader
Marilyn
M
Keck School of Medicine, University of Southern California, Department of Physiology and Biophysics, 1333 San Pablo St., MMR 624, Los Angeles, CA 90033, USA. ader@hsc.usc.edu
Garvey
W Timothy
WT
Phillips
Lawrence S
LS
Nemeroff
Charles B
CB
Gharabawi
Georges
G
Mahmoud
Ramy
R
Greenspan
Andrew
A
Berry
Sally A
SA
Musselman
Dominique L
DL
Morein
Jacqueline
J
Zhu
Young
Y
Mao
Lian
L
Bergman
Richard N
RN
D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D010054:Brief Psychiatric Rating Scale; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007333:Insulin Resistance / Q000208:ethnology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D014150:Antipsychotic Agents; D001786:Blood Glucose; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine