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Prevalence of obesity, metabolic syndrome, diabetes and risk of cardiovascular disease in a psychiatric inpatient sample: results of the Metabolism in Psychiatry (MiP) Study.
Barton, BB, Zagler, A, Engl, K, Rihs, L, Musil, R
European archives of psychiatry and clinical neuroscience. 2020;(5):597-609
Abstract
The information on prevalence of obesity, diabetes, metabolic syndrome (MetS) and cardiovascular risk (CVR) and on sociodemographic variables available in patients with psychiatric diseases about to be treated with weight gain-associated medication (e.g., clozapine, mirtazapine, quetiapine) is limited. In a naturalistic study, psychiatric inpatients (age: 18-75) of all F diagnoses according to ICD-10, who were about to be treated with weight gain-associated medication, were included. Demographic variables were assessed as well as biological parameters to calculate the Body Mass Index (BMI), MetS, diabetes and CVR. A total of 163 inpatients were included (60.1% male; mean age: 39.8 (± 15.1, 18-75 years). The three most common disorders were depression (46.0%), bipolar disorder (20.9%) and drug addiction (20.2%). The three most common pharmacotherapeutic agents prescribed were quetiapine (29.4%), mirtazapine (20.9%) and risperidone (12.9%). Of the included inpatients 30.1% were overweight, 17.2% obese, and 26.9% and 22.4% fulfilled the criteria for a MetS according to the International Diabetes Federation (IDF) and the National Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III), respectively, 3.8% had (pre)diabetes and 8.3% had a moderate and 1.9% a high CVR according to the Prospective Cardiovascular Münster (PROCAM) score. Detailed information is reported on all assessed parameters as well as on subgroup analyses concerning sociodemographic variables. The results suggest that psychiatric patients suffer from multiple metabolic disturbances in comparison to the general population. Monitoring weight, waist circumference, blood pressure and cholesterol regularly is, therefore, highly relevant.
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CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine.
Siskind, D, Friend, N, Russell, A, McGrath, JJ, Lim, C, Patterson, S, Flaws, D, Stedman, T, Moudgil, V, Sardinha, S, et al
BMJ open. 2018;(3):e021000
Abstract
INTRODUCTION Clozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation. METHODS AND ANALYSIS A 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants. ETHICS AND DISSEMINATION Ethics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds. TRIAL REGISTRATION NUMBER ACTRN12617001547336; Pre-results.
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Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review.
Gurusamy, J, Gandhi, S, Damodharan, D, Ganesan, V, Palaniappan, M
Asian journal of psychiatry. 2018;:73-85
Abstract
INTRODUCTION Individuals with major psychotic disorders such as schizophrenia are at increased risk for developing metabolic syndrome due to lifestyle- and treatment-related factors. Numerous interventions have been tested in inpatient and outpatient mental health settings to decrease risk factors. Diet and exercise represent the mainstay of weight loss treatment. With this background the review aimed to evaluate the effects of psychoeducation, diet and physical activity interventions on reduction of metabolic syndrome risk factors such as BMI, Body weight, biochemical profiles in schizophrenia. METHODS The authors conducted database searches of PsychINFO, MEDLINE, Pubmed, Proquest, EBSCO and the Cochrane Database of Systematic Reviews, and manual searches from 1968 to 2017. Search indentified 11 studies that met the inclusion criteria. Study quality was critically appraised by 2 reviewers using established criteria. The outcome measures were body mass index, body weight, waist circumference, lipid profile, fasting glucose. RESULTS Interventions led to significant weight reduction (8 studies), reduced body mass index (5 studies), decreased waist circumference (4 studies) and lower blood glucose levels (5 studies). Dietician and nurse led interventions (6 studies). The studies showed non pharmacological interventions were effective in reducing risk factors. CONCLUSION This review was able to demonstrate effectiveness of peychoeducation, diet and physical activity interventions were helpful to decrease and manage antipsychotic-induced weight gain. Results showed lifestyle interventions are safer and effective for promoting decrease or maintenance of weight and it can be delivered at low cost, safe and improves quality of life.
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Eight weeks of overfeeding alters substrate partitioning without affecting metabolic flexibility in men.
Peterson, CM, Zhang, B, Johannsen, DL, Ravussin, E
International journal of obesity (2005). 2017;(6):887-893
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Abstract
BACKGROUND/OBJECTIVE Impairments in metabolic flexibility (MF) and substrate handling are associated with metabolic syndrome. However, it is unknown whether metabolic inflexibility causes insulin resistance. We therefore measured MF and substrate handling before and after 8 weeks of overfeeding in initially healthy adults as a model of the early stages of insulin resistance. SUBJECTS/METHODS Twenty-nine healthy men (27±5 years old; body mass index 25.5±2.3 kg m-2) were overfed by 40% above baseline energy requirements for 8 weeks and gained 7.6±2.1 kg of weight. Before and after overfeeding, energy expenditure, substrate oxidation and MF were measured in two ways: (a) during 1 day of eucaloric feeding in a whole-room indirect calorimeter and (b) during a two-step hyperinsulinemic-euglycemic clamp. RESULTS Eight weeks of overfeeding decreased insulin sensitivity at low and high doses of insulin (P=0.001 and P=0.06, respectively). This was accompanied by decreases in the respiratory quotient (RQ) while sleeping (from 0.877±0.020 to 0.864±0.026; P=0.05) and at low insulin levels during the clamp (from 0.927±0.047 to 0.907±0.032; P=0.01). Overfeeding did not affect MF as measured during a clamp (P⩾0.17), but it tended to increase 24-h MF (awake RQ-sleep RQ) as measured by chamber by 0.010±0.028 (P=0.08). In terms of substrate oxidation, overfeeding increased protein oxidation by 13±23 g day-1 (P=0.003) and tended to increase fat oxidation by 6±16 g day-1 (P=0.07) but did not affect carbohydrate oxidation (P=0.64). Individuals with greater metabolic adaptation to overfeeding had higher carbohydrate oxidation rates (r=0.66, P=8 × 10-5) but not fat oxidation rates (P=0.09). CONCLUSIONS The early stages of insulin resistance are accompanied by modest declines in the RQs during sleep and during a clamp, with no changes in fasting RQ or signs of metabolic inflexibility. Our data therefore suggest that metabolic inflexibility does not cause insulin resistance.
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Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study.
Ferjan, S, Janez, A, Jensterle, M
Metabolic syndrome and related disorders. 2017;(10):515-520
Abstract
BACKGROUND Weight loss is often nonsustainable after liraglutide cessation. The present study is the first insight into the potential prevention of weight regain in obese subjects who have been withdrawn from liraglutide. We evaluated whether dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in adjunct to metformin prevents body weight regain more effectively than metformin alone in obese polycystic ovary syndrome (PCOS) previously treated with liraglutide. METHODS A 12-week prospective randomized open-label study was conducted with 24 obese women with PCOS who had been pretreated with liraglutide 3.0 mg due to antiobesity management (aged 34.3 ± 6.8 years, body mass index [BMI] 36.3 ± 5.2 kg/m2, mean ± standard deviation). They were randomized to combined treatment (COMBO) with sitagliptin 100 mg per day (QD) and metformin (MET) 1000 mg twice daily (BID) (n = 12) or MET 1000 mg BID (n = 12). Lifestyle intervention was promoted in both groups. The primary outcome was change in anthropometric measures of obesity. RESULTS Women treated with MET regain 4.7 ± 2.7 kg (P = 0.002) compared with a 0.9 ± 2.5 kg in COMBO (P = 0.147). BMI increased for 1.7 ± 0.9 kg/m2 in MET (P = 0.002) compared with 0.3 ± 0.8 kg/m2 increase in COMBO (P = 0.136). MET group regain 4.5% ± 2.5% of body weight as opposed to 0.8% ± 2.6% in COMBO. The between-treatment differences were significant for weight change (P < 0.001), percentage of weight change (P < 0.001), and BMI change (P < 0.001). Greater ability to resist emotional eating was demonstrated in COMBO. CONCLUSION Sitagliptin in adjunct to metformin prevented weight regain in obese women with PCOS previously treated with liraglutide.
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Use of Metformin for Cardiometabolic Risks in Psychiatric Practice: Need-to-Know Safety Issues.
Andrade, C
The Journal of clinical psychiatry. 2016;(11):e1491-e1494
Abstract
Metformin, a biguanide drug, is emerging as an important treatment option for the prevention or treatment of weight gain, type 2 diabetes mellitus, and the metabolic syndrome in psychiatric patients, especially those who require or receive antipsychotic drugs. Metformin treatment is commonly associated with gastrointestinal adverse effects; the risk of these is reduced by gradual dose uptitration, administration of the drug with meals, and use of a time-release formulation. Lactic acidosis, a potentially fatal complication of biguanide therapy, is very rare with metformin; the risk can be reduced by avoidance of its prescription in patients with impaired renal function, impaired liver function, cardiac failure, and certain other conditions. Long-term metformin use is associated with decreased vitamin B₁₂ levels, and even with biochemical B₁₂ deficiency; this complication can detected early by annual assessments of serum B₁₂ levels and prevented by annual intramuscular B₁₂ administration.
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Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis.
Siskind, DJ, Leung, J, Russell, AW, Wysoczanski, D, Kisely, S
PloS one. 2016;(6):e0156208
Abstract
BACKGROUND Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. METHODS We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. RESULTS Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. CONCLUSIONS Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. TRIAL REGISTRATION PROSPERO registration number: CRD42015029723.
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Metabolic issues in psychotic disorders with the focus on first-episode patients: a review.
Britvic, D, Maric, NP, Doknic, M, Pekic, S, Andric, S, Jasovic-Gasic, M, Popovic, V
Psychiatria Danubina. 2013;(4):410-5
Abstract
Before the onset of the illness, future schizophrenia patients do not weigh more comparing to their peers. However, during the later course of the illness, obesity is twice as prevalent as in general public, afflicting the half of schizophrenia patient population. There is a list of potential factors that contribute to this, including lifestyle, dietary habits, unsatisfactory monitoring of physical health etc, but nowadays side effects of antipsychotic medication become the most prominent concern when weight gain and metabolic issues in psychosis are addressed. The fact is that second generation antipsychotics (SGA) are associated with weight gain and metabolic syndrome, but that might be the case with the first generation antipsychotics (FGA) too. Besides, obesity might be evident in patients before any exposure to medications, and all that bring lot of dilemmas into the field. This paper critically reviews available data on metabolic problems in patients with psychotic disorders, raging from genetic to molecular and environmental factors, and highlights the necessity of screening for the early signs of metabolic disturbances, as well as of multidisciplinary assessment of psychiatric and medical conditions from the first psychotic episode.
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Weight-loss-associated changes in bone mineral density and bone turnover after partial weight regain with or without aerobic exercise in obese women.
Hinton, PS, Rector, RS, Linden, MA, Warner, SO, Dellsperger, KC, Chockalingam, A, Whaley-Connell, AT, Liu, Y, Thomas, TR
European journal of clinical nutrition. 2012;(5):606-12
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BACKGROUND/OBJECTIVES Moderate, long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women. However, whether these changes persist during weight maintenance or regain remains to be determined. SUBJECTS/METHODS Overweight or obese (body mass index: 25.8-42.5 kg/m(2)) women (n=40) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain, with or without exercise, on bone turnover and on bone mineral density (BMD) in a subset of participants (n=24). During the first 6 month, participants lost ≈ 10% of their initial body weight via energy restriction and supervised aerobic exercise. Following weight loss, participants were randomly assigned to either an exercise or a no exercise treatment for the regain (+50% of weight lost) phase. A one-way (time) repeated measures one-factor analysis of variance (RMANOVA) tested the effects of weight loss on BMD and bone turnover, and a two-way RMANOVA (time, exercise) was used to examine the effects of exercise during weight regain. RESULTS Hip (P=0.007) and lumbar spine (P=0.05) BMD decreased with weight loss, and remained reduced after weight regain with or without exercise. Likewise, the weight-loss-associated increases in osteocalcin (P<0.001) and C-terminal peptide of type I collagen (P<0.001) persisted following weight regain, independent of exercise. CONCLUSIONS The results of the present study, which is the first to examine changes in bone mass and turnover during carefully controlled weight regain, suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain, regardless of whether regular weight-bearing aerobic exercise was continued.
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Metabolic syndrome and mental illness. Weight gain and other unhealthy attributes increase risk of diabetes and heart disease.
The Harvard mental health letter. 2011;(2):5