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.
"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. "
[Show abstract][Hide abstract] 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.
"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. "
[Show abstract][Hide abstract] 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
"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. "
[Show abstract][Hide abstract] 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 · 5.94 Impact Factor
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