Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia

Abstract

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.

Fig. 1

Comparison of time course of body weight gain between antipsychotic treatment groups (least squares mean ± SE). Statistics for treatment differences are based on ANCOVA, with center and treatment as the main effects and baseline as covariate. Both treatments were associated with significant weight gain over baseline throughout study period (weeks 1 through 24; p < 0.004 for each). There was a significantly greater weight gain with olanzapine compared to risperidone at weeks 5 (p < 0.05) and 12 (<0.03).

Fig. 2

Changes in (A) total adiposity or (B) visceral adiposity during antipsychotic treatment in the entire study population. * p < 0.02 vs. baseline. ** p < 0.003 vs. baseline. *** p < 0.0007 vs. baseline.

Fig. 3

Changes in (A) total adiposity or (B) visceral adiposity during antipsychotic treatment in African American and Hispanic subjects. * p < 0.02 vs. baseline. ** p < 0.007 vs. baseline. §p < 0.04 vs. risperidone.