Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.
ABSTRACT While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes.
To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test.
A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis.
Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis.
Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness.
The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine<olanzapine<risperidone), with subjects who received clozapine and olanzapine exhibiting significant insulin resistance compared with subjects who were treated with risperidone (clozapine vs risperidone, t(33) = -4.29; P<.001; olanzapine vs risperidone, t(33) = -3.62; P = .001 [P<.001]). The homeostasis model assessment of insulin resistance also differed significantly among groups (F(33) = 4.92; P = .01) (clozapine>olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03).
Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences.
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ABSTRACT: Abstract Objective: Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia-related psychotic disorders and contributes to increased rates of premature death due to cardiovascular disease. This study examined the impact of switching from another antipsychotic to ziprasidone on the distribution of the number of risk factors for MetS in subjects with schizophrenia or related psychotic disorders. Research Design and Methods: In this 1-year, open-label, prospective study, all subjects received ziprasidone 40-160 mg/day. Standard exclusion criteria included treatment resistance, physical health disorders, and substance abuse. The primary end point was the percentage of subjects achieving a reduction from baseline of at least 1 risk factor for MetS at end point (week 52 or premature discontinuation) in the per-protocol population (treated for at least 16 weeks). Secondary end points included the mean change from baseline in number of MetS risk factors, the prevalence of MetS, individual MetS risk factors (waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose), and 10-year coronary heart disease (Framingham score) risk. Clinical trial registration: www.clinicaltrials.gov : NCT00748566. Main Outcome Measures: Of 114 evaluable subjects, 58.77% demonstrated 1 less MetS risk factor at week 52 (last observation carried forward) compared with baseline. Secondary end points also improved, with reductions in other metabolic parameters (low-density lipoprotein cholesterol, total cholesterol, weight, body mass index, glycosylated hemoglobin [HbA1c], and insulin). The 10-year coronary heart disease risk decreased continually over time. The open-label and uncontrolled design is a limitation of the study. Conclusions: Ziprasidone treatment reduced both the rate of MetS and its individual risk factors in subjects with schizophrenia and related psychotic disorders. The results have implications for the selection of first-line treatments in schizophrenia and related psychotic disorders, and provide treatment options for subjects who have developed MetS as a result of other antipsychotics.Current Medical Research and Opinion 02/2014; · 2.37 Impact Factor
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