Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.

We have previously demonstrated that the glucocorticoid receptor ß (GRß) isoform induces hepatic steatosis in mice fed a normal chow diet. The GRß isoform inhibits the glucocorticoid-binding isoform GRα, reducing responsiveness and inducing glucocorticoid resistance. We hypothesized that GRß regulates lipids that cause metabolic dysfunction. To determine the effect of GRß on hepatic lipid classes and molecular species, we overexpressed GRß (GRß-Ad) and vector (Vec-Ad) using adenovirus delivery, as we previously described. We fed the mice a normal chow diet for 5 days and harvested the livers. We utilized liquid chromatography-mass spectrometry (LC-MS) analyses of the livers to determine the lipid species driven by GRß. The most significant changes in the lipidome were monoacylglycerides and cholesterol esters. There was also increased gene expression in the GRß-Ad mice for lipogenesis, eicosanoid synthesis, and inflammatory pathways. These indicate that GRß-induced glucocorticoid resistance may drive hepatic fat accumulation, providing new therapeutic advantages.

The role of small dense LDL-C/large buoyant LDL-C ratio as an independent risk factor in patients with type 2 diabetes mellitus and metabolic syndrome

Dyslipidemia plays a key role in metabolic syndrome (MS), intricately linked to type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences in low-density lipoprotein cholesterol (LDL-C) subfraction levels between T2DM and T2DM with MS, and identify the risk factors associated with the disease. A total of 246 individuals diagnosed with T2DM, including 144 T2DM patients with MS, and 147 healthy subjects were recruited. All participants underwent a comprehensive clinical evaluation. Lipoprotein subfraction analysis was performed using the Lipoprint LDL system. Multivariate logistic regression analysis revealed that several lipid markers, including triglyceride (TG), LDL-C, large buoyant LDL-C (lbLDL-C), small dense LDL-C (sdLDL-C), LDLC2-5, and sdLDL-C/lbLDL-C ratio, were identified as independent risk factors for T2DM. Additionally, TG, sdLDL-C, LDLC-4, LDLC-5, and sdLDL-C/lbLDL-C ratio were found to be independent risk factors for T2DM with MS. Furthermore, the results of the receiver operating characteristic (ROC) curves demonstrated that sdLDL-C, LDLC-4, LDLC-3, and sdLDL-C/lbLDL-C ratio exhibited excellent predictive performance for the risk of T2DM (AUC > 0.9). The sdLDL-C/lbLDL-C ratio emerges as a shared independent risk factor for T2DM and MS complications. Furthermore, sdLDL-C/lbLDL-C ratio, along with LDL-4 and LDL-3, exhibits noteworthy predictive capabilities for T2DM.

Associations between multiple urinary metals and metabolic syndrome: Exploring the mediating role of liver function in Chinese community-dwelling elderly.

BACKGROUND: Multiple metals exposure has been revealed to be related to metabolic syndrome (MetS). However, the associations and interactions between multiple metals exposure and MetS are remains controversial, and the potential mechanism of the above-mentioned is still unclear. METHODS: The associations between urinary metals and the MetS were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Bayesian kernel machine regression (BKMR) model and quantile-based g-computation (qgcomp) were applied to explore the mixed exposure and interaction effect of metals. Mediation analysis was used to explore the role of liver function. RESULTS: In the single metal model, multiple metals were significantly associated with MetS. RCS analysis further verified the associations between 8 metals and MetS. BKMR model and qgcomp showed that zinc (Zn), iron (Fe), and tellurium (Te) were the main factors affecting the overall effect. In addition, mediation analysis indicated that serum alanine aminotransferase (ALT) mediated 21.54% and 13.29% in the associations of vanadium (V) and Zn with the risk of MetS, respectively. CONCLUSIONS: Elevated urinary concentration of Zn, V, Te, copper (Cu), molybdenum (Mo), and thallium (Tl) were related to the increased risk of MetS. Conversely, Fe and selenium (Se) may be protective factors for MetS in mixed exposure. Liver function may play a key role in the association of V and Zn exposure with MetS.

Anti-adipogenesis and anti-obesity potential of alliin mediated by modulating glycolipid metabolism via activating PPARγ signaling.

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products.

Mediterranean diet in the targeted prevention and personalized treatment of chronic diseases: evidence, potential mechanisms, and prospects.

The prevalence of chronic diseases is currently a major public health issue worldwide and is exploding with the population growth and aging. Dietary patterns are well known to play a important role in our overall health and well-being, and therefore, poor diet and malnutrition are among the most critical risk factors for chronic disease. Thus, dietary recommendation and nutritional supplementation have significant clinical implications for the targeted treatment of some of these diseases. Multiple dietary patterns have been proposed to prevent chronic disease incidence, like Dietary Approaches to Stop Hypertension (DASH) and Diabetes Risk Reduction Diet (DRRD). Among them, the MedDiet, which is one of the most well-known and studied dietary patterns in the world, has been related to a wide extent of health benefits. Substantial evidence has supported an important reverse association between higher compliance to MedDiet and the risk of chronic disease. Innovative strategies within the healthcare framework of predictive, preventive, and personalized medicine (PPPM/3PM) view personalized dietary customization as a predictive medical approach, cost-effective preventive measures, and the optimal dietary treatment tailored to the characteristics of patients with chronic diseases in primary and secondary care. Through a comprehensive collection and review of available evidence, this review summarizes health benefits of MedDiet in the context of PPPM/3PM for chronic diseases, including cardiovascular disease, hypertension, type 2 diabetes, obesity, metabolic syndrome, osteoporosis, and cancer, thereby a working hypothesis that MedDiet can personalize the prevention and treatment of chronic diseases was derived.

Antenatal glycemic management and postpartum cardiovascular disease risk screening.

OBJECTIVE: This study aims to evaluate the cardiovascular disease (CVD) risk profiles of patients referred to the maternal health clinic (MHC) with a history of gestational diabetes (GDM). METHODS: Eligible patients had their MHC appointment at 6 months postpartum between November 2011 and May 2022 and experienced GDM in their most recent pregnancy. Included participants were then divided into subgroups comparing methods of glycemic control: diet-controlled GDM and insulin-controlled GDM. Additionally, the MHC recruited 47 patients who have not experienced a complication in pregnancy to act as a comparator group in research studies. Demographics, medical and pregnancy history, and CVD risk scores were compared between the three groups. RESULTS: 344 patients with GDM were included in the analysis; 165 insulin-controlled and 179 diet-controlled. When measuring the median 30 year Framingham risk score based on both BMI and lipids, there was a significant stepwise increase seen from the unexposed group, the diet-controlled GDM, and the insulin-controlled groups, respectively (all P < 0.05). The presence of metabolic syndrome showed a stepwise increase in prevalence when comparing the unexposed group, diet exposure group, and the insulin exposure group, respectively (16.7%, 21.5%, 44.8%; P < 0.05). CONCLUSION: Our findings reinforce the prevalence of maternal CVD risk among GDM-diagnosed patients in the postpartum period and the necessity for screening. More specifically, our findings show how CVD risk may differ based on required interventions for glycemic control throughout pregnancy. Future research should aim to compare a more diverse patient population to optimize the generalizability of glycemic control-specific CVD outcomes.

Lymphocyte to High-density Lipoprotein Cholesterol Ratio is Positively Associated with Pre-diabetes, Metabolic Syndrome, and Non-traditional Cardiometabolic Risk Markers: A Cross-sectional Study at Secondary Health Care.

High scores of lymphocyte-to-high-density lipoprotein cholesterol ratio (lymphocyte-to-HDL-c) may be a new indicator of inflammation and metabolic syndrome. Here, we investigated the associations of the lymphocyte-to-HDL-c with traditional and non-traditional cardiometabolic risk markers in subjects at high cardiovascular risk. This study is a cross-sectional analysis with subjects assisted in a Secondary Health Care (n = 581, age = 63.06 ± 13.86 years; 52.3% women). Lymphocyte-to-HDL-c ratio were assessed by routine laboratory tests. Anthropometric and/or biochemical variables were used to calculate traditional (body mass index - BMI, and waist-to-height ratio - WHtR) and non-traditional (lipid accumulation product index-LAP, visceral adiposity index-VAI, deep-abdominal-adipose-tissue index-DAAT, atherogenic index of plasma-AIP, and waist-hypertriglyceridemic phenotype-HTGW) cardiometabolic risk markers. Furthermore, anthropometric measurement waist circumference (WC), blood pressure, metabolic syndrome (MS), and biochemical markers (lipid and glycemic profile) were considered traditional markers of cardiometabolic risk. Pearson's chi-square test, Poisson regression with robust variance, or multinomial logistic regression were performed (α = 0.05). Individuals with a high lymphocyte-HDL-c ratio (> 0.84, 3rd tertile) were associated with the HTGW phenotype, high VAI, high LAP, hypertriglyceridemia, high AIP, high very low-density lipoprotein-cholesterol (VLDL-c), pre-diabetes, and 3 and 4 MS components compared with individuals in the first tertile, independent of confounders. Our findings supported the lymphocyte-to-HDL-c ratio as a potential biomarker during the screening of subjects at high cardiovascular risk.

The combined effect of cardiorespiratory and muscular fitness on the incidence of metabolic syndrome before midlife.

BACKGROUND: Cardiorespiratory fitness (CRF) could reduce the risk of metabolic syndrome (MetS) while the association between muscular endurance capacity (MEC) and incident MetS has rarely been investigated in young adults. METHODS: A total of 2890 military men and women, aged 18-39 years, free of baseline MetS in Taiwan, were followed for incident MetS from baseline (2014) until the end of 2020. All subjects received annual health examinations for assessment of MetS. Physical fitness was assessed by CRF (estimated maximal oxygen uptake, VO2 max [mL/kg/min], in a 3000-m run) and MEC (numbers of 2-min push-ups). MetS was defined according to the International Diabetes Federation (IDF) criteria. Multiple Cox regression analysis was conducted with adjustments for baseline age, sex, substance use status and physical activity to determine the associations of CRF and MEC with incidences of new-onset MetS and related features, for example, central obesity, hypertension, dyslipidaemia and prediabetes or diabetes. To examine the combined effects of CRF and MEC status on incidence of MetS, high and low levels of CRF and MEC were separately defined by over and under the sex-specific median in each exercise test. RESULTS: During a median follow-up of 5.8 years, there were 673 (23.3%) new-onset MetS. Higher CRF was associated with a lower incidence of MetS (hazard ratio [HR] and 95% confidence interval: 0.905 [0.877-0.933]), and its components separately, except hypertension. No association was observed between MEC and incident MetS, and its components separately, except hypertension. When evaluating the combined effects of MEC and CRF status on the incidence of MetS, it was observed that compared with the low CRF/low MEC, the high CRF/high MEC (HR: 0.553 [0.439-0.697]) and the high CRF/low MEC (HR: 0.730 [0.580-0.918]) had a lower incidence of new-onset MetS (P value for the intergroup difference = 0.04). There was no significant result for the low CRF/high MEC. CONCLUSIONS: This study highlights that although the protective effects of MEC to reduce the incidence of MetS and most of its related features were mainly driven by CRF in young adults, there was an addictive effect of greater MEC on CRF to prevent the development of new-onset MetS before midlife.

The prevalence of frailty among patients with metabolic syndrome: a systematic review and meta-analysis.

Background: Growing evidence shows that metabolic syndrome and frailty are significantly associated. Screening and assessing frailty in patients with metabolic syndrome is important to help improve their clinical outcomes and quality of life. Therefore, understanding the prevalence of frailty in patients with metabolic syndrome is the first critical step, however, the prevalence reported in the literature varies widely.Aim: To pool the overall prevalence of frailty among patients with metabolic syndrome.Design: Systematic review and meta-analysis.Methods: The Cochrane Library, PubMed, Web of Science, Embase, APA PsycINFO, Scopus, CINAHL Complete, CNKI, Wan Fang, SinoMed, and VIP databases were searched from the inception to March 6, 2024. Statistical analysis was performed using STATA15 software. The prevalence was pooled using the random-effects model. The sources of heterogeneity were investigated by using meta-regression and subgroup analyses.Results: A total of 22 original studies published between 2007 and 2023 were included in this systematic review and meta-analysis, involving 19,921 metabolic syndrome patients. The prevalence of frailty and pre-frailty among patients with metabolic syndrome was 20% (95% CI: 16% to 25%, I2 = 99.44%) and 45% (95% CI: 36% to 53%, I2 = 99.20%). Subgroup analyses revealed differences in prevalence by frailty instruments, geographic regions, study settings, publication years, study quality, study design, and different components of metabolic syndrome.Conclusions: This systematic review and meta-analysis showed the high prevalence of frailty and pre-frailty in patients with metabolic syndrome. In the future, more high-quality longitudinal studies and exploration of other potential demographic characteristics that may influence frailty are needed to understand more information on frailty in patients with metabolic syndrome.

Relationship between metabolic syndrome and depression: A study based on Rafsanjan Youth Cohort Study.

BACKGROUND: Depressed people are susceptible to metabolic syndrome ression and metabolic syndrome in the Rafsanjan Youth Cohort Study in 2021. METHODS: In this cross-sectional study, the data of 3005 young people aged 15-35 under the coverage of urban and rural health centers was investigated in the enrollment stage of the Rafsanjan Youth Cohort Study as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Data was collected using face-to-face interview and electronic questionnaires of the Rafsanjan Youth Cohort Study. RESULTS: Age of the youth was 25.78 ±â€¯6.06 years, 56 % (n = 1682) were female. The prevalence of metabolic syndrome (MetS) was 7.7 % (95 % CI: 6.8 %-8.8 %) and the prevalence of depression was 11.1 % (95 % CI: 10.0 %-12.3 %). Depression did not have a significant impact on the odds ratio of developing MetS in young people (P = 0.604). The odds ratio (OR) of MetS increases by 1.057 times with increasing age (95 % CI for OR: 1.020-1.094). This OR is also 1.715 times higher in married young people than in unmarried Youth (95 % CI for OR: 1.715-2.692) and 0.196 times lower in young people with medium and high MET index than in young people with low MET index (95 % CI for OR: 0.048-0.811). LIMITATIONS: Inability to determine a causal relationship between MetS and depression. CONCLUSION: Due to the growing trend of components of MetS among the young population, this issue needs to be addressed in future policies and planning for prevention and control as a health priority.

Impact of metabolic syndrome factors on sperm DNA fragmentation in males from infertile couples: A systematic review and meta-analysis.

PURPOSE: To investigate the impact of metabolic syndrome factors on sperm DNA fragmentation (sDF) in males from infertile couples. METHODS: A systematic literature search was performed across ten databases for literature published from January 1, 2013 until September 13, 2023. The protocol has been registered on PROSPERO (CRD42023458359), and the literature search strategy is adhered to the PRISMA framework. Studies that evaluated sDF, as indicated by DNA fragmentation index (%DFI), in males from infertile couples in relation to metabolic syndrome factors were included. Meta-analysis, using random effects model and Bayesian framework network, was performed, and data were presented as Standardized Mean Differences (SMD) with corresponding 95% Confidence Interval (CI). RESULTS: Of the 2579 citations identified, eleven studies were included in this meta-analysis. The findings revealed that the %DFI was not associated with overall metabolic syndrome factors (p-tot=0.235; SMD=0.57 [95%CI: -0.37, 1.52]), metabolic syndrome status (p-tot=0.337; SMD=0.08 [95%CI: -0.08, 0.24), increased body mass index (p-tot=0.237; SMD=0.71 [95%CI: -0.47, 1.89]), or glycaemic profile (p-tot=0.93; SMD=0.13 [95%CI: -2.72, 2.98]). High levels of heterogeneity were observed (p < 0.01) in all subgroups, except for metabolic syndrome status. CONCLUSION: The association between metabolic syndrome factors and sDF is conflicting. However, interpreting the association requires caution, as confounding factors, indicated by high heterogeneity, may conceal the outcome. Metabolic syndrome may influence other factors contributing to male infertility, highlighting the importance of promoting a healthy lifestyle.

The triglyceride-glucose index is superior to homeostasis model assessment of insulin resistance in predicting metabolic syndrome in an adult population in the United States.

BACKGROUND: Metabolic Syndrome (MetS) is a cluster of cardio-metabolic features portending an increased risk for both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a widely used surrogate measure of insulin resistance. The triglyceride-glucose (TyG) index is another validated measure of insulin resistance that predicts both diabetes and cardiovascular disease in low and medium-income countries, but only diabetes in high income countries. OBJECTIVE: Due to the paucity of data on the TyG index in the US population, we compared the validity of the TyG index and HOMA-IR in predicting MetS. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 on Non-Hispanic White(NHW), Hispanic American(HA), and African American(AA) individuals(n = 5380) aged 20-80 years were used for analysis. Individuals were classified as having MetS based on three or more of its components. HOMA-IR and the TyG index were determined from fasting samples. RESULTS: Both the TyG index and HOMA-IR were significantly increased in MetS and increased significantly with increasing severity of the syndrome. Also both indices correlated significantly with all 5 features of MetS, hsCRP and non-HDL-C. ROC-AUC analysis for TyG index was significantly greater than that of HOMA-IR in predicting MetS: 0.87(95 % CI 0.85-0.88) versus 0.82(95 % CI 0.81-0.83) respectively, p < 0.0001. This was not evident for the small AA subgroup. CONCLUSION: The TyG index outperformed HOMA-IR in predicting MetS, a proxy for both T2DM and ASCVD, in a general US population and is a valuable biomarker.

Effects of different fractions of polysaccharides from Dictyophora indusiata on high-fat diet-induced metabolic syndrome in mice.

Dictyophora indusiata is a common edible mushroom with great potential in the field of medicine against metabolic disorders, inflammation, and immunodeficiency. Our previous studies have shown that different fractions of the polysaccharide from Dictyophora indusiata (DIP) have various structural characteristics and morphology. However, the impact of the structural features on the protective effects of DIP against metabolic syndrome remains unclear. In this study, three distinct polysaccharide fractions have been extracted from Dictyophora indusiata and a high-fat diet-induced metabolic syndrome (MetS) was constructed in mice. The effects of these fractions on a range of MetS-associated endpoints, including abnormal blood glucose, lipid profiles, body fat content, liver function, intestinal microbiota and their metabolites were investigated. Through correlation analysis, the potential link between the monosaccharide composition of the polysaccharides and their biological activities was determined. The study aimed to explore the potential mechanisms and ameliorative effects of these polysaccharide fractions on MetS, thereby providing statistical evidence for understanding the relationship between monosaccharides composition of Dictyophora indusiata polysaccharides and their potential utility in treating metabolic disorders.

The circadian syndrome is a predictor for cognition impairment in middle-aged adults: Comparison with the metabolic syndrome.

AIMS: Circadian syndrome (CircS) is considered a better predictor for cardiovascular disease than the metabolic syndrome (MetS). We aim to examine the associations between CircS and MetS with cognition in Chinese adults. METHOD: We used the data of 8546 Chinese adults aged ≥40 years from the 2011 China Health and Retirement Longitudinal Study. MetS was defined using harmonised criteria. CircS included the components of MetS plus short sleep and depression. The cut-off for CircS was set as ≥4. Global cognitive function was assessed during the face-to-face interview. RESULTS: CircS and MetS had opposite associations with the global cognition score and self-reported poor memory. Compared with individuals without the CircS and MetS, the regression coefficients (95%CI) for global cognition score were -1.02 (-1.71 to -0.34) for CircS alone and 0.52 (0.09 to 0.96) for MetS alone in men; -1.36 (-2.00 to -0.72) for CircS alone and 0.60 (0.15 to 1.06) for MetS alone in women. Having CircS alone was 2.53 times more likely to report poor memory in men (95%CI 1.80-3.55) and 2.08 times more likely in women (95%CI 1.54-2.81). In contrast, having MetS alone was less likely to report poor memory (OR 0.64 (0.49-0.84) in men and 0.65 (0.52-0.81) in women). People with CircS and MetS combined were more likely to have self-reported poor memory. CONCLUSIONS: CircS is a strong and better predictor for cognition impairment than MetS in Chinese middle-aged adults. MetS without short sleep and depression is associated with better cognition.

Increased prevalence of metabolic syndrome in female patients with overactive bladder: A population-based study.

OBJECTIVES: To assess the association between overactive bladder syndrome (OAB) and the metabolic syndrome (MetS). PATIENTS AND METHODS: A population-based study was conducted to compare OAB patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of the parameters of the MetS, with respect to obesity, hyperlipidemia, hypertension and diabetes mellitus. The characteristics of the OAB population were assessed. Adjusted odds ratios (OR) were calculated by logistic regression. RESULTS: 110 024 OAB patients and 220 455 controls. were identified. OAB was associated with a higher prevalence of MetS (35.4% vs. 27.5%, p < 0.001). The fully adjusted OR for MetS in patients with OAB compared to controls was 1.44; 95% confidence interval (CI) 1.42-1.46; p < 0.001. Among metabolic parameters, obesity was found to be the strongest factor associated with OAB (OR 1.55, 95% CI 1.53-1.58, p < 0.001), and higher high-density lipoprotein cholesterole levels (>50) had a protective effect on the risk of OAB (OR 0.75, 95% CI 0.73-0.76, p < 0.001). CONCLUSIONS: Data from this cohort suggest that OAB is positively associated with MetS. Clinicians approaching patients with OAB should be aware of this association. A multimodal treatment focusing on the MetS may be considered in these patients.

Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis.

Background: Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. Method: We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Results: Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Conclusion: Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

Links Between Adipose Tissue Gene Expression of Gut Leakage Markers, Circulating Levels, Anthropometrics, and Diet in Patients with Coronary Artery Disease.

Background: Recent studies suggest gut-derived lipopolysaccharide (LPS)-translocation to play a role in both systemic inflammation and in inflammatory adipose tissue. We aimed to investigate whether circulating LPS-related inflammatory markers and corresponding genetic expression in adipose tissue were associated with obesity, cardiometabolic risk factors, and dietary habits in patients with coronary artery disease. Methods: Patients (n=382) suffering a myocardial infarction 2-8 weeks prior to inclusion were enrolled in this cross-sectional study. Subcutaneous adipose tissue (SAT), taken from the gluteal region, and fasting blood samples were collected at inclusion for determination of genetic expression of LPS-binding protein (LBP), CD14, toll-like receptor 2 (TLR2), and TLR4 in SAT, and LPS, LBP, and soluble cluster of differentiation 14 (sCD14) in the circulation. All patients filled out a dietary registration form. Results: Patients (median age 74 years, 25% women), had a median body mass index (BMI) of 25.9 kg/m2. Circulating levels of LBP correlated to BMI (p=0.02), were significantly higher in overweight or obese (BMI≥25 kg/m2) compared to normal- or underweight patients (BMI<25 kg/m2), and were significantly elevated in patients with T2DM, hypertension, and MetS, compared to patients without (p≤0.04, all). In SAT, gene expression of CD14 and LBP correlated significantly to BMI (p≤0.001, both), and CD14 and TLR2 expressions were significantly higher in patients with T2DM and MetS compared to patients without (p≤0.001, both). Circulating and genetically expressed CD14 associated with use of n-3 PUFAs (p=0.008 and p=0.003, respectively). No other significant associations were found between the measured markers and dietary habits. Conclusion: In patients with established CAD, circulating levels of LBP and gene expression of CD14 and TLR2 in SAT were related to obesity, MetS, T2DM, and hypertension. This suggests that the LPS-LBP-CD14 inflammatory axis is activated in the chronic low-grade inflammation associated with cardiometabolic abnormalities, whereas no significant associations with dietary habits were observed.

Obstructive Sleep Apnea Syndrome and Obesity Indicators, Circulating Blood Lipid Levels, and Adipokines Levels: A Bidirectional Two-Sample Mendelian Randomization Study.

Purpose: This investigation sought to elucidate the genetic underpinnings that connect obesity indicators, circulating blood lipid levels, adipokines levels and obstructive sleep apnea syndrome (OSAS), employing a bidirectional two-sample Mendelian randomization (MR) analysis that utilizes data derived from extensive genome-wide association studies (GWAS). Methods: We harnessed genetic datasets of OSAS available from the FinnGen consortium and summary data of four obesity indices (including neck circumference), seven blood lipid (including triglycerides) and eleven adipokines (including leptin) from the IEU OpenGWAS database. We primarily utilized inverse variance weighted (IVW), weighted median, and MR-Egger methods, alongside MR-PRESSO and Cochran's Q tests, to validate and assess the diversity and heterogeneity of our findings. Results: After applying the Bonferroni correction, we identified significant correlations between OSAS and increased neck circumference (Odds Ratio [OR]: 3.472, 95% Confidence Interval [CI]: 1.954-6.169, P= 2.201E-05) and decreased high-density lipoprotein (HDL) cholesterol levels (OR: 0.904, 95% CI: 0.858-0.952, P= 1.251E-04). Concurrently, OSAS was linked to lower leptin levels (OR: 1.355, 95% CI: 1.069-1.718, P= 0.012) and leptin receptor levels (OR: 0.722, 95% CI: 0.530-0.996, P= 0.047). Sensitivity analyses revealed heterogeneity in HDL cholesterol and leptin indicators, but further multiplicative random effects IVW method analysis confirmed these correlations as significant (P< 0.05) without notable heterogeneity or horizontal pleiotropy in other instrumental variables. Conclusion: This investigation compellingly supports the hypothesis that OSAS could be a genetic predisposition for elevated neck circumference, dyslipidemia, and adipokine imbalance. These findings unveil potential genetic interactions between OSAS and metabolic syndrome, providing new pathways for research in this domain. Future investigations should aim to delineate the specific biological pathways by which OSAS impacts metabolic syndrome. Understanding these mechanisms is critical for developing targeted prevention and therapeutic strategies.

Addressing causal relationship between drinking behavior and metabolic syndrome: one-sample Mendelian randomization analysis.

AIMS: Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis. METHODS: A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30-70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model. RESULTS: A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p < .001), 1.31 (1.23, 1.40, p < .001), and 1.87 (1.75, 2.00, p < .001), respectively, for the weighted genetic risk score. CONCLUSIONS: This study shows a modest relationship between drinking behavior and MetS by using MR analysis.