Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease.

BACKGROUND: Weight gain following initiation of antiretroviral therapy (ART) is common. We assessed the impact of changes in weight in the year following ART initiation with subsequent cardiometabolic disease among AIDS Clinical Trials Group (ACTG) participants. METHODS: Linear regression models were fit to examine the association between change in weight/waist circumference (WC) in weeks 0-48 and change in metabolic parameters in weeks 0-48 and 48-96. Cox proportional hazard models were fit to examine the association between changes in weight/WC in weeks 0-48 and diabetes mellitus (DM), metabolic syndrome, or cardiometabolic and cardiovascular events after week 48. RESULTS: Participants (N = 2624) were primarily male (81%) and non-White (60%). Mean weight gain from 0-48 weeks was 3.6 kg (SD 7.3); 130 participants developed DM; 360 metabolic syndrome; 424 any cardiometabolic event; 28 any cardiovascular event, over 480 weeks of follow-up. In adjusted models, total cholesterol increased by 0.63 mg/dL (95% confidence interval [CI] [.38, .089]) and LDL by 0.39 mg/dL (0.19, 0.59) per 1 kg increase in weight from weeks 0 to48. Participants who experienced >10% weight gain (vs -5% to 5%) had an increased risk of DM (hazard ratio [HR] 2.01, 95% CI [1.30, 3.08]), metabolic syndrome (HR 2.24, 95% CI [1.55, 2.62]), and cardiometabolic outcomes (HR 1.54, 95% CI [1.22, 1.95]). Participants who lost more than 5% of their baseline weight had a lower risk of incident metabolic syndrome (HR 0.67, 95% CI [0.42, 1.07]). Trends for WC were similar. CONCLUSIONS: Weight and body composition changes in the first year following ART initiation are associated with contemporaneous changes in metabolic parameters and subsequent cardiometabolic disease.

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

Associations between exposure to various air pollutants and risk of metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Metabolic Syndrome (MetS) is a widely observed metabolic disorder that is increasingly prevalent worldwide, leading to substantial societal consequences. Previous studies have conducted two separate meta-analyses to investigate the relationship between MetS and air pollutants. However, these studies yielded conflicting results, necessitating a thorough systematic review and meta-analysis to reassess the link between different air pollutants and the risk of developing MetS. METHODS: We conducted a comprehensive search of relevant literature in databases including PubMed, Embase, Cochrane Library, and Web of Science up to October 9, 2023. The search was specifically restricted to publications in the English language. Following the screening of studies investigating the correlation between air pollution and MetS, we utilized random-effects models to calculate pooled effect sizes along with their respective 95% confidence intervals (CIs). We would like to highlight that this study has been registered with PROSPERO, and it can be identified by the registration number CRD42023484421. RESULTS: The study included twenty-four eligible studies. The results revealed that an increase of 10 µg/m3 in annual concentrations of PM1, PM2.5, PM10, NO2, SO2, and O3 was associated with a 29% increase in metabolic syndrome (MetS) risk for PM1 (OR = 1.29 [CI 1.07-1.54]), an 8% increase for PM2.5 (OR = 1.08 [CI 1.06-1.10]), a 17% increase for PM10 (OR = 1.17 [CI 1.08-1.27]), a 24% increase for NO2 (OR = 1.24 [CI 1.01-1.51]), a 19% increase for SO2 (OR = 1.19 [CI 1.04-1.36]), and a 10% increase for O3 (OR = 1.10 [CI 1.07-1.13]). CONCLUSION: The findings of this study demonstrate a significant association between exposure to fine particulate matter (PM1, PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and the incidence of metabolic syndrome (MetS). Moreover, the results suggest that air pollution exposure could potentially contribute to the development of MetS in humans.

Associations of multiple serum metals with the risk of metabolic syndrome among the older population in China based on a community study: A mediation role of peripheral blood cells.

Metal exposure has been reported to be associated with metabolic syndrome (MetS), however, the evidence remains inconclusive, particularly in elderly individuals. From May to July 2016, serum levels of 16 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) in 852 elderly individuals (≥65 years) residing in Wuhan, China. Biological detection and disease recognition were based on individual surveys conducted during health check-ups. Spearman's rank correlation analysis was performed to identify the correlation among serum metals. The data were Ln-transformed to fit a normal distribution for further analyses. Linear and logistic regression were applied to explore the associations between metals and diseases. Restricted cubic spline (RCS) analysis was utilized to examine dose-response relationships. The Weighted Quantile Sum (WQS) score was applied to determine the empirical weights of each heavy metal in the context of their combined effect on metabolic diseases. The prevalence of MetS, hypertension, diabetes, and hyperlipidemia were 46.36 %, 68.90 %, 24.65 %, and 21.60 %, respectively. Serum metal mixture was positively associated with the prevalence of MetS (OR = 1.92, 95 % CI: 1.30-2.82), hypertension (OR = 1.50, 95 % CI: 1.01-2.23), and diabetes (OR = 2.18, 95 % CI: 1.48-3.22). In single metal models, we found that serum zinc levels were associated with an increased risk of MetS, while rubidium had a protective effect against MetS. Interestingly, different metals had distinct effects on specific diseases in this study: lithium and barium were more likely to influence blood pressure, while selenium had a more significant effect on blood glucose. Lipids were more susceptible to the effects of zinc, selenium, and strontium. Platelet count (PLT) and lymphocyte count (LYM) mediated the association between selenium exposure and hyperlipidemia, while neutrophil count (NEU) mediated the relationship between serum rubidium exposure and MetS. Our findings offer valuable etiological insights into the relationship between serum heavy metals and the prevalence of MetS, suggesting that peripheral blood cells may play a mediating role in this association.

Association between endocrine-disrupting chemical mixtures and non-alcoholic fatty liver disease with metabolic syndrome as a mediator among adults: A population-based study in Korea.

Endocrine-disrupting chemicals (EDCs) may play a role in non-alcoholic fatty liver disease (NAFLD); however, studies on the combined effects of EDC mixtures on NAFLD development are limited. Here, we explored the association between exposure to EDC mixtures and NAFLD and investigated the potential mediating role of metabolic syndrome (MetS). We included participants from the Korean National Environmental Health Survey Cycle 4 (2018-2020) and quantified the urinary concentrations of various EDCs-eight phthalate metabolites, three phenols, one antibacterial compound, four parabens, four polycyclic aromatic hydrocarbons, and one pyrethroid pesticide metabolite-as well as serum concentrations of five perfluorinated compounds (PFCs). NAFLD was defined as a hepatic steatosis index (HSI) ≥36 or a fatty liver index (FLI) ≥60. Weighted quantile sum (WQS) regression was employed to evaluate the associations between EDC mixtures and the risk of MetS or NAFLD. Causal mediation analysis was conducted to explore the potential mediating effect of MetS on the association between mixtures of EDCs and NAFLD risk. All estimates were adjusted for age, sex, educational level, physical activity, smoking status, involuntary smoking, and drinking habits. A total of 2942 adults were included in the analysis. Moderate-to-high positive correlations were identified between phthalate metabolites and PFCs. Higher WQS scores were associated with an elevated risk of MetS and NAFLD. The sex-stratified WQS regression model showed that the interactions between the WQS index and sex were significant for MetS and NAFLD. According to the causal mediation analysis, both the direct and indirect effects of EDC mixtures on NAFLD, with MetS as a mediator, were significant in females. Collectively, these findings highlight the need for interventions that could address both EDC mixture exposure and metabolic status to effectively reduce the risks associated with NAFLD and its related complications.

Mechanism and treatments of antipsychotic-induced weight gain.

The long-term use of antipsychotics (APs) may cause a variety of diseases, such as metabolic syndrome, antipsychotic-induced weight gain (AIWG), and even obesity. This paper reviews the various mechanisms of AIWG and obesity in detail, involving genetics, the central nervous system, the neuroendocrine system, and the gut microbiome. The common drug and non-drug therapies used in clinical practice are also introduced, providing the basis for research on the molecular mechanisms and the future selection of treatments.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Lurasidone and risk of metabolic syndrome: results from short and long-term studies in patients with bipolar depression.

OBJECTIVE: The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression. METHODS: Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision). RESULTS: The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group. CONCLUSIONS: This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.

Lifestyle behaviors, metabolic disturbances, and weight gain in psychiatric inpatients treated with weight gain-associated medication.

Many psychiatric patients suffer from overweight/obesity and subsequent metabolic disturbances, where psychotropic medication is one of the main contributors. However, the magnitude of weight gain ranges individually, which leads to questioning the role of other contributors like lifestyle factors. The present study investigated several lifestyle factors among psychiatric inpatients, their relation to biological factors, and their predictive capability for weight gain during treatment. Using a naturalistic observational study design, psychiatric inpatients of all diagnoses were followed for 4 weeks from the start of treatment with weight gain-associated medication. N = 163 participants entered the study. Lifestyle factors were assessed by patient self-report questionnaires. Body weight change over time was calculated relative to baseline body weight. Our study provides three main findings: (1) Obesity and/or metabolic syndrome (metSy) were associated with emotional eating (disinhibition), craving for fast food and sweets, and weight cycling. (2) Patients without metSy and normal BMI experienced increased sweets craving (also for women), a more positive attitude towards drugs, and an improvement of affect (also for men). (3) Sex, presence of metSy and/or drug dosage interacted with disinhibition change, sweets craving change (trend), and fast food craving change to predict weight change over time. Furthermore, drug attitude change interacted with BMI, drug dosage, and presence of metSy to predict weight change. Lifestyle factors, especially eating behaviors, are related to metabolic disturbances and predict weight gain in interaction with clinical parameters.

Cross-sectional associations between phthalates, phenols, and parabens with metabolic syndrome risk during early-to-mid adolescence among a cohort of Mexican youth.

BACKGROUND: Epidemiological studies on children and adults have linked toxicants from plastics and personal care products to metabolic disruption. Yet, the impact of endocrine-disrupting chemicals (EDCs) on adolescent metabolic syndrome (MetS) risk during early and mid-adolescence is unclear. METHODS: To examine the links between exposure to EDCs and MetS risk and its components, cross-sectional data from 344 Mexican youth in early-to-mid adolescence (10-17 years) were analyzed. Urinary biomarker concentrations of phthalates, phenol, and paraben analytes were measured from a single spot urine sample collected in 2015; study personnel obtained anthropometric and metabolic measures. We examined associations between summary phthalates and metabolites, phenol, and paraben analytes with MetS risk z-scores using linear regression, adjusted for specific gravity, sex, age, pubertal status, smoking, alcohol intake, physical activity level, and screen time. As a secondary aim, mediation analysis was conducted to evaluate the role of hormones in the association between summary phthalates with lipids and MetS risk z-scores. RESULTS: The mean (SD) age was 13.2 (1.9) years, and 50.9% were female. Sex-stratified analyses revealed associations between summary phthalates and lipids ratio z-scores, including Σ DEHP [ß = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [ß = 0.24 (95% CI: 0.03, 0.44; p < 0.05)] was positively associated with lipids ratio z-score and one phenol (2,5 DCP) [ß = 0.09 (95% CI: 0.01, 0.18); p < 0.05)] was associated with increased waist circumference z-score. Results showed no evidence of mediation by hormone concentrations in the association between summary phthalates with lipids ratio or MetS risk z-scores. CONCLUSION: Higher EDC exposure was positively associated with serum lipids during adolescence, particularly among males.

Long-term effects of ambient PM2.5 constituents on metabolic syndrome in Chinese children and adolescents.

Metabolic syndrome (MetS) is considered a main public health issue as it remarkably adds the risk of cardiovascular disease, leading to a heavy burden of disease. There is growing evidence linking fine particulate matter (PM2.5) exposure to MetS. However, the influences of PM2.5 constituents, especially in children and adolescents, remain unclear. Our study was according to a national analysis among Chinese children and adolescents to examine the associations between long-term exposure to PM2.5 main constituents and MetS. A total of 10,066 children and adolescents aged 10-18 years were recruited in 7 provinces in China, with blood tests, health exams, and questionnaire surveys. We estimated long-term exposures to PM2.5 mass and its five constituents, containing black carbon (BC), organic matter (OM), inorganic nitrate (NO3-), sulfate (SO42-), and soil particles (SOIL) from multi-source data fusion models. Mixed-effects logistic regression models were used with the adjustment of a variety of covariates. In the surveyed populations, 2.9% were classified as MetS. From the single-pollutant models, we discovered that long-term exposures to PM2.5 mass, BC, OM, NO3-, as well as SO42-, were significantly associated with the prevalence of MetS, with odds ratios (ORs) per 1 µg/m3 that were 1.02 (95% confidence interval (CI): 1.01, 1.03) for PM2.5 mass, 1.24 (95% CI: 1.14, 1.35) for BC, 1.07 (95% CI: 1.04, 1.11) for OM, 1.09 (95% CI: 1.04, 1.13) for NO3-, and 1.14 (95% CI:1.04, 1.24) for SO42-. The influence of BC on the prevalence of MetS was robust in both the multi-pollutant model and the PM2.5-constituent joint model. The paper indicates long-term exposure to PM2.5 mass and specific PM2.5 constituents, particularly for BC, was significantly associated with a higher MetS prevalence among children and adolescents in China. Our results highlight the significance of establishing further regulations on PM2.5 constituents.

Lithium plus antipsychotics or anticonvulsants for bipolar disorder: Comparing clinical response and metabolic changes.

OBJECTIVE: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. METHODS: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4-0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. RESULTS: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP (N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) (p = 0.59). Users of Li+AC (N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC (N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general (p = 0.05) and manic symptoms (p = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome. CONCLUSION: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic.

Nurse-led lifestyle intervention in a cohort of schizophrenia patients treated with clozapine.

Patients diagnosed with schizophrenia are characterized by early mortality compared to the general population. The main cause of this premature death reflects medical complications linked to metabolic syndrome (MetS). The use of antipsychotics such as clozapine is associated with weight gain and metabolic disturbances in certain predisposed individuals. Non-pharmacological interventions for weight control have become a key element for secondary prevention in the health of patients diagnosed with schizophrenia. Here, we aim to evaluate the physical health effects of a nurse-led non-pharmacological intervention program in patients with a diagnosis of schizophrenia treated with clozapine. Thirty-one outpatients from the outpatient clinical facility of Hospital Clinic in Barcelona, Spain diagnosed with schizophrenia and other psychotic disorders receiving clozapine treatment were enrolled in a prospective interventional study, comprising an 8-week group program of therapeutic education in a healthy lifestyle. MetS factors, physical activity, diet, and lifestyle were evaluated at baseline, post-intervention (8 weeks), and 3 months after the program. Weight, body mass index, high-density lipoprotein cholesterol, and diet patterns displayed significant differences post-intervention and after 3 months, while only waist, hip perimeter, and lifestyle improved post-intervention. Our results suggest the effectiveness of the lifestyle intervention in patients under clozapine treatment despite its long-time differential effect. Strategies to prevent weight gain and metabolic decline will help prevent premature cardiometabolic disease in this vulnerable population.

Associations of long-term exposure to ambient air pollutants with metabolic syndrome: The Wuhan Chronic Disease Cohort Study (WCDCS).

BACKGROUND: Evidence on the associations between long-term exposure to ambient air pollutants (including particle with aerodynamic diameter ≤10 µm (PM10), particle with aerodynamic diameter ≤2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2)) and prevalence of metabolic syndrome (MetS) remains inconclusive. This study aimed to determine the associations based on a case-control study nested in the Wuhan Chronic Disease Cohort study (WCDCS), a population-based study with baseline survey in 2019. METHODS: A total of 10,253 residents living in Wuhan were recruited. The 3-year average concentrations of main pollutants (PM10, PM2.5, O3, NO2, and SO2) at residences prior to the survey date were estimated to evaluate the long-term exposures. The generalized linear mixed models were used to investigate the changes in MetS prevalence by an IQR increases in each air pollutant exposure concentrations. Interaction effects between air pollutants and demographic, lifestyle, and dietary factors on MetS were evaluated by including an interactive item in the main model. RESULTS: The prevalence of MetS in Wuhan was 9.8%, and the 3-year exposure concentrations of PM10, PM2.5, O3, NO2, and SO2 were 84.1 µg/m3, 50.5 µg/m3, 55.7 µg/m3, 46.0 µg/m3, and 9.4 µg/m3, respectively. Higher PM10, PM2.5 and O3 exposure concentrations were associated with an elevated MetS prevalence (e.g. an IQR increase in PM2.5, OR = 1.193, 95% confidence intervals (95%CIs): 1.028, 1.385; for O3, OR = 1.074, 95%CIs: 1.025, 1.124), whereas NO2, and SO2 were negatively or insignificant correlated with odds of Mets (e.g. an IQR increase in NO2, OR = 0.865, 95%CIs: 0.795, 0.941). Males, smokers, alcohol drinkers and individuals who intake fruits occasionally exposure to PM10 and PM2.5 were found had a higher risk of developing MetS. CONCLUSIONS: Long-term exposure to higher concentrations of ambient air pollutants may elevate the prevalence of MetS in populations in Central China. Susceptible individuals especially those with unhealthy lifestyles had a higher risk for MetS.

Association of environmental tobacco smoke exposure with metabolic syndrome: A longitudinal Cohort Study of 71,055 never smokers.

BACKGROUND AND AIMS: Effects of environmental tobacco smoke (ETS) exposure and a change in ETS exposure status on metabolic syndrome (MetS) remain unknown. Thus, the aim of this study was to evaluate the effect of ETS exposure on MetS in self-reported and cotinine-validated never smokers. METHODS AND RESULTS: From a large longitudinal cohort study, 71,055 cotinine-validated never smokers without MetS at baseline were included. These participants were divided into four groups (no, new, former, and continuous ETS exposure groups) based on their ETS exposure status at baseline and follow-up. The association between ETS exposure and MetS was assessed using multivariable Cox hazard regression analyses. During a median follow-up of 33 months, 15.0 cases/10,000 person-years (PY) developed MetS. Incidence rates per 10,000 PY of MetS in no, new, former, and continuous ETS exposure groups were 14.0, 18.5, 16.5, and 19.0, respectively. In multivariable Cox hazard regression analyses, the new and continuous ETS exposure groups showed increased risk of MetS compared to the no ETS exposure group (hazard ratio [95% confidence interval]: 1.35 [1.16, 1.56], p-value < 0.001 for the new ETS exposure group and 1.19 [1.06, 1.34], p-value = 0.004 for the continuous ETS exposure group). However, the former ETS exposure group did not show an increased risk of MetS (0.96 [0.88, 1.05], p-value = 0.36). CONCLUSION: This study showed that ETS exposure and changes in ETS exposure status over approximately three years could modify the risk of MetS, suggesting that avoidance of ETS may not increase the risk of incidence of MetS.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

STUDY OBJECTIVES: Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. METHODS: Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 "F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. RESULTS: Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51-2.72] for each ten-kg/m2 increase), central obesity (OR = 2.20, [1.63-2.96]), hypertension (OR = 1.86, [1.23-2.81]), hyperglycemia (OR = 3.70, [2.16-6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17-1.95]), metabolic syndrome (OR = 1.84, [1.16-2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17-1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. CONCLUSIONS: Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis.

OBJECTIVE: Metabolic side effects are a limiting factor in the use of antipsychotics, which remain the cornerstone of long-term management of patients with severe mental illness. There is contrasting evidence on a possible role of melatonin and melatonin-agonists in attenuating antipsychotic-induced metabolic abnormalities. DESIGN: We conducted a systematic review (PubMed, PsycInfo, Cochrane databases, up to August 2020) and a random-effect meta-analysis of double-blind, randomized placebo-controlled trials (RCTs) involving melatonin and melatonin-agonists in the treatment of antipsychotic-induced metabolic changes. The primary outcome was the standardized mean difference (SMD) of composite metabolic outcomes built with metabolic syndrome components. Secondary outcomes were individual metabolic syndrome components, and other anthropometric, glucose metabolism, lipid profile, and psychopathology measures. RESULTS: Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia-spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD -0.28, 95% CI = -0.39 ÷ -0.168), as well as on all individual components of metabolic syndrome (systolic blood pressure MD -3.266, 95% CI = -6.020 ÷ -0.511; fasting glucose MD -3.766, 95% CI = -5.938 ÷ -1.593; triglycerides MD -9.800, 95% CI = -19.431 ÷ -0.169; HDL MD 2.995, 95% CI = 0.567 ÷ 5.423), except waist circumference. CONCLUSIONS: Melatonin/ramelteon augmentation may be beneficial for non-anthropometric metabolic syndrome components in patients treated with antipsychotics.

Empagliflozin in kidney transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome: Five Japanese cases.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert cardiorenal protective effects in diabetic patients and are widely used clinically. In addition, an increasing number of reports now suggest these drugs may even be beneficial in non-diabetic patients. However, SGLT2 inhibitors are rarely prescribed for kidney transplant recipients due to the risk of renal graft damage and urogenital infections. CASE PRESENTATION: We report the cases of 5 renal transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome who were administered the SGLT2 inhibitor empagliflozin, which yielded beneficial results in 4 cases. With the exception of one patient with an initial estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m2, administration of empagliflozin elicited beneficial metabolic effects. There were no significant reductions in eGFR before or after empagliflozin administration, and no dehydration or urogenital infections were observed during the treatment course. CONCLUSION: Empagliflozin showed some positive effects in 4 cases with better renal function than CKD stage 4. Further studies will be required to clarify the efficacy and safety of SGLT2 inhibitors in a larger group of patients with similar medical conditions.

Dose-dependent association between inhaled corticosteroid use and risk of obesity and metabolic syndrome in asthma.

Background: Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. Objective: To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome. Methods: A 5-year retrospective two-arm cohort study explored patients on asthma and not on ICS relative to patients with asthma who were on varying doses of ICS (low, medium, and high) and attributes such as body mass index (BMI) trajectory and prescription of antihypertensive, antidiabetic, and cholesterol-lowering medications. Results: A total of 229 subjects with asthma were in the control cohort, and 215 subjects with asthma were in the ICS cohort. The ICS cohort was subdivided into individuals on low- (n = 88), medium- (n = 107), or high- (n = 20) dose ICS throughout the 5-year study period. For every 1-year increase in time, the BMI in the high-dose ICS group increased at a rate of 0.25 kg/m² when compared with the subjects in the control group after controlling for age and gender. Also, for every 1-year increase in time, the BMI of those on medium-dose ICS increased by 0.06 kg/m² compared with those in the control group after controlling for age and gender. The subjects on ICS also had a statistically increased risk of being prescribed antihypertensive, antidiabetic, and cholesterol-lowering medications. Conclusion: ICS use in the subjects with asthma was associated with a dose-dependent risk of increasing BMI trajectories over time and an increased requirement for antidiabetic and cholesterol-lowering medications. One possible conclusion from this study is that long-term medium- and high-dose ICS have the potential to induce systemic effects.