Prediabetes in Patients Treated With Antipsychotic Drugs

Zucker Hillside Hospital, Glen Oaks, NY 11004, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2011; 73(4):460-6. DOI: 10.4088/JCP.10m06822
Source: PubMed


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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    • "Medication-induced carbohydrate craving and/or reduced activity levels because of sedation cause weight gain (Elmslie et al., 2001). Especially the use of second generation antipsychotics (SGAs) is associated with glucose dysregulation (Guo et al., 2006; Manu et al., 2012, 2014). "
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    ABSTRACT: Background: Abnormalities in the glucose metabolism cause nervous and organic damage and are a cardiovascular risk factor. They could be a main cause for the increased morbidity and mortality rates found in patients with bipolar disorders. The exact prevalence of diabetes and pre-diabetic abnormalities, however, is not clear. Methods: 85 euthymic outpatients with bipolar disorders from two university hospitals in Germany underwent an oral glucose tolerance test, laboratory screening and clinical measurements. Socio-demographic data, medication, severity of illness, global functioning and life quality were assessed. Results: Diabetes mellitus was found in 7% of the patients, pre-diabetic abnormalities in 27%. The group of patients with abnormalities in the glucose metabolism had significantly lower quality of life and global functioning. Higher BMI, leptin, triglycerides and CRP levels significantly increased the likelihood for pre-diabetes/diabetes. Limitations: The low sample size did only allow limited assessment of impact of medication on the results. No healthy controls were assessed. Conclusions: One-third of the patients with bipolar disorders showed abnormalities in the glucose metabolism and this was associated with impaired global functioning and lower quality of life. Early detection and intervention strategies fitting the needs of patient with bipolar disorder are needed to improve both physical and mental health.
    Journal of Affective Disorders 09/2015; 189. DOI:10.1016/j.jad.2015.09.041 · 3.38 Impact Factor
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    • "Neuropharmacology atypical antipsychotics have a reduced liability to trigger extrapyramidal side effects, they induce intolerable metabolic side effects (Manu et al., 2012). Therefore, it remains critical to identify additional therapeutic mechanisms for treatment of psychotic symptoms associated with schizophrenia and other psychiatric disorders. "
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    ABSTRACT: Studies described here tested the hypothesis that phosphodiesterase 10A inhibition by a selective antagonist, MP-10, activates the dopamine D2 receptor expressing medium spiny neurons to a greater extent than the D1 receptor expressing neurons. We used regional pattern of c-Fos induction in the neostriatal subregions of rodents and direct assessment of D1-positive and-negative neurons in the DRd1a-tdTomato mice for the purpose. MP-10 (1, 3, 10 or 30 mg/kg, PO) dose-dependently increased c-Fos immunopositive nuclei in all regions of neostriatum. However, the effect was statistically greater in the dorsolateral striatum, a region known to be activated preferentially by the D2 antagonism, than the D1-activated dorsomedial striatum. The D2 antagonist, haloperidol (0.3, 1, or 3 mg/kg, PO) produced an identical, regional pattern of c-Fos induction favoring the dorsolateral striatum of the rat. In contrast, the D1 agonist, SKF82958 (0.5, 1, or 2 mg/kg, PO), induced greater expression of c-Fos in the dorsomedial striatum. The C57Bl/6 mouse also showed regionally preferential c-Fos activation by haloperidol (2 mg/ kg, IP) and SKF82858 (3 mg/kg, IP). In the Drd1a-tdTomato mice, MP-10 (3 or 10 mg/kg, IP) increased c-Fos immunoreactivity in both types of neurons, the induction was greater in the D1-negative neurons. Taken together, both the regional pattern of c-Fos induction in the striatal sub-regions and the greater induction of c-Fos in the D1-negative neurons indicate that PDE10A inhibition produces a small but significantly greater activation of the D2-containing striatopallidal pathway.
    Neuropharmacology 07/2015; 99:379-386. DOI:10.1016/j.neuropharm.2015.08.008 · 5.11 Impact Factor
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    • "Among patients with metabolic syndrome, the relative risk for type 2 DM and coronary heart disease is 1.5–5 times that of the general population (26). Numerous studies have reported high rates of metabolic syndrome in atypical treated patients, with prevalence rates of over 50% for prediabetes or type 2 DM in some adult psychiatric inpatient settings (27–29). In the large head-to-head clinical trial of atypical antipsychotics, the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) Study (a major, multi-center trial sponsored by NIMH) observed that 43% of patients treated with atypicals had metabolic syndrome. "
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    ABSTRACT: Psychotic disorders most commonly appear during the late teenage years and early adulthood. A focused and rapid clinical response by an integrated health team can help to improve the quality of life of the patient, leading to a better long-term prognosis. The Vancouver Coastal Health early psychosis intervention program covers a catchment area of approximately 800,000 people in the cities of Vancouver and Richmond, Canada. The program provides a multidisciplinary approach to supporting patients under the age of 30 who have recently experienced first-break psychosis. The program addresses the needs of the treatment environment, medication, and psychological therapies. A critical part of this support includes a program to specifically improve patients' physical health. Physical health needs are addressed through a two-pronged, parallel approach. Patients receive routine metabolic health assessments during their first year in the program, where standard metabolic parameters are recorded. Based on the results of clinical interviews and laboratory tests, specific actionable interventions are recommended. The second key strategy is a program that promotes healthy lifestyle goal development. Patients work closely with occupational therapists to develop goals to improve cardiometabolic health. These programs are supported by an active research environment, where patients are able to engage in studies with a focus on improving their physical health. These studies include a longitudinal evaluation of the effects of integrated health coaching on maintaining cardiometabolic health in patients recently admitted to the program, as well as a clinical study that evaluates the effects of low versus higher metabolic risk antipsychotic drugs on central adiposity. An additional pharmacogenomic study is helping to identify genetic variants that may predict cardiometabolic changes following treatment with antipsychotic drugs.
    Frontiers in Psychiatry 09/2014; 5:105. DOI:10.3389/fpsyt.2014.00105
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