Prediabetes in Patients Treated With Antipsychotic Drugs

Zucker Hillside Hospital, Glen Oaks, NY 11004, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 12/2011; 73(4):460-6. DOI: 10.4088/JCP.10m06822
Source: PubMed

ABSTRACT In 2010, the American Diabetes Association (ADA) proposed that individuals with fasting glucose level of 100-125 mg/dL (5.6-6.9 mmol/L) or glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) 2 hours after a 75-g oral glucose tolerance test or hemoglobin A(1c) 5.7%-6.4% be classified as prediabetic, indicating increased risk for the emergence of diabetes mellitus. At the same time, the ADA formulated guidelines for the use of metformin for the treatment of prediabetes.
To determine the prevalence of prediabetes in a cohort of psychiatrically ill adults receiving antipsychotics and to compare the clinical and metabolic features of prediabetic patients with those of patients with normal glucose tolerance and those with diabetes mellitus.
The 2010 ADA criteria were applied to a large, consecutive, single-site European cohort of 783 adult psychiatric inpatients (mean age: 37.6 years) without a history of diabetes who were receiving antipsychotics. All patients in this cross-sectional study underwent measurement of body mass index (BMI), waist circumference, oral glucose tolerance test, and fasting insulin and lipids from November 2003 through July 2007.
413 patients (52.8%) had normal glucose tolerance, 290 (37.0%) had prediabetes, and 80 (10.2%) had diabetes mellitus. The fasting glucose and/or hemoglobin A(1c) criteria were met by 89.7% of prediabetic patients. A statistically significant intergroup gradient from normal glucose tolerance to prediabetes and from prediabetes to diabetes mellitus was observed for waist circumference, triglycerides, fasting insulin levels, and frequency of metabolic syndrome (P = .02 to P < .0001). Only 19/290 prediabetic patients (6.6%) met the 2010 ADA criteria for treatment with metformin.
Prediabetes is highly prevalent in adults treated with antipsychotic drugs and correlates with markers of increased intraabdominal adiposity, enhanced lipolysis, and insulin resistance. Criteria for using metformin to prevent the emergence of diabetes mellitus may need to be revised for this population.

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Available from: Marc De Hert, Jul 28, 2015
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    • "We further propose that optimal monitoring for MDD patients, and standard monitoring for those taking antipsychotics, should also include fasting lipids and hemoglobin A1C (HbA1c) and/or fasting blood glucose. HbA1c has the advantage of not requiring a fasting sample and is reported to identify a larger number of patients with early, only post-prandial hyperglycemia/pre-diabetes (Manu et al. 2012, 2013). A recent study (Mitchell et al., unpublished observations ) proposes the optimal testing protocol with a HbA1c threshold 55.7% followed by conventional testing with an oral glucose tolerance test and fasting blood glucose in patients who test positive. "
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    ABSTRACT: Individuals with depression have an elevated risk of cardiovascular disease (CVD) and metabolic syndrome (MetS) is an important risk factor for CVD. We aimed to clarify the prevalence and correlates of MetS in persons with robustly defined major depressive disorder (MDD). We searched Medline, PsycINFO, EMBASE and CINAHL up until June 2013 for studies reporting MetS prevalences in individuals with MDD. Medical subject headings 'metabolic' OR 'diabetes' or 'cardiovascular' or 'blood pressure' or 'glucose' or 'lipid' AND 'depression' OR 'depressive' were used in the title, abstract or index term fields. Manual searches were conducted using reference lists from identified articles. The initial electronic database search resulted in 91 valid hits. From candidate publications following exclusions, our search generated 18 studies with interview-defined depression (n = 5531, 38.9% male, mean age = 45.5 years). The overall proportion with MetS was 30.5% [95% confidence interval (CI) 26.3-35.1] using any standardized MetS criteria. Compared with age- and gender-matched control groups, individuals with MDD had a higher MetS prevalence [odds ratio (OR) 1.54, 95% CI 1.21-1.97, p = 0.001]. They also had a higher risk for hyperglycemia (OR 1.33, 95% CI 1.03-1.73, p = 0.03) and hypertriglyceridemia (OR 1.17, 95% CI 1.04-1.30, p = 0.008). Antipsychotic use (p < 0.05) significantly explained higher MetS prevalence estimates in MDD. Differences in MetS prevalences were not moderated by age, gender, geographical area, smoking, antidepressant use, presence of psychiatric co-morbidity, and median year of data collection. The present findings strongly indicate that persons with MDD are a high-risk group for MetS and related cardiovascular morbidity and mortality. MetS risk may be highest in those prescribed antipsychotics.
    Psychological Medicine 11/2013; 44(10):1-12. DOI:10.1017/S0033291713002778
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    • "Weight and height were used to calculate BMI. Fasting glucose and insulin levels were used to assess insulin resistance according to the homeostatic model assessment (HOMA-IR) [19]. Glucose and insulin levels measured after glucose challenge were used to calculate the area under the curve (AUC) for glucose and insulin. "
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    ABSTRACT: BACKGROUND: Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI=25-29.9) without metabolic syndrome or diabetes has not been thoroughly investigated. OBJECTIVE: To assess the metabolic health of overweight patients receiving antipsychotic drugs. METHODS: We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes. RESULTS: Compared with the normal weight subjects (n=286), overweight patients (n=212) had higher fasting insulin resistance as assessed with the homeostatic model (P=0.023), insulin secretion during the oral glucose tolerance test (P=0.0037), triglycerides (P=0.0004) and low-density lipoprotein cholesterol (P=0.0089), and lower levels of high-density lipoprotein cholesterol (P=0.0014). The obese (n=50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P=0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups. CONCLUSIONS: Overweight (BMI=25-29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.
    European Psychiatry 02/2013; 29(3). DOI:10.1016/j.eurpsy.2012.12.001
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    • "The present study investigated the insulin secretion in a large cohort of non-diabetic patients treated with four widely used second-generation antipsychotic drugs, i.e., clozapine, olanzapine, quetiapine and risperidone, which are known to lead to weight accrual and to increase the risk of the emergence of metabolic syndrome (Newcomer, 2005; De Hert et al., 2012; Correll et al., in press) and prediabetes (Manu et al., 2012). The study confirmed that fasting insulin levels and degree of insulin resistance are greater in prediabetic patients. "
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    ABSTRACT: BACKGROUND: Second-generation antipsychotics (SGAs) increase the risk of type 2 diabetes. The mechanism is thought to center on drug-induced weight gain, which starts the dysmetabolic cascade of insulin resistance, increased insulin production and pancreatic beta-cell failure. An independent effect of SGAs on insulin secretion has been suggested in animal models, but has not been demonstrated in clinical samples. OBJECTIVE: To determine the post-challenge insulin secretion in patients treated with SGAs. METHOD: We identified 520 non-diabetic individuals treated with clozapine (N=73), olanzapine (N=190), quetiapine (N=91) or risperidone (N=166) in a consecutive, single-site cohort of 783 adult psychiatric inpatients who underwent a comprehensive metabolic assessment. Insulin secretion was measured as the area under the curve (AUC(insulin)) generated by levels recorded at baseline, 30, 60 and 120min after the intake of 75g of glucose. The independent predictors of insulin secretion were determined with regression analysis in the entire sample and separately in patients with normal glucose tolerance (NGT) and prediabetes. RESULTS: The post-challenge AUC(insulin) was independently predicted by AUC(glucose), waist circumference, triglyceride levels and younger age (p<0.0001); non-smoking status (p=0.0012); and treatment with clozapine (p=0.021). The model explained 33.5% of the variance in insulin secretion (p<0.0001). The clozapine effect was present in the NGT group, but not in prediabetics. CONCLUSIONS: Clozapine, but not olanzapine, quetiapine and risperidone, is an independent predictor of post-challenge insulin secretion in non-diabetics, particularly in those with normal glucose tolerance. The findings suggest that the diabetogenic risk of clozapine may persist even after weight reduction.
    Schizophrenia Research 12/2012; 143(2-3). DOI:10.1016/j.schres.2012.11.016
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