Metabolically Healthy Obese Research Articles

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis.

Evidence of the effects of metabolically healthy obesity (MHO) on atherosclerosis is limited; the transition effects of metabolic health and obesity phenotypes have been ignored. We examined the association between metabolic health and the transition to atherosclerosis risk across body mass index (BMI) categories in a community population. This cross-sectional study was based on a national representative survey that included 50,885 community participants aged ≥40years. It was conducted from 01 December 2017 to 31 December 2020, in 13 urban and 13 rural regions across Hunan China. Metabolic health was defined as meeting less than three abnormalities in blood pressure, glucose, high-density lipoprotein cholesterol, triglycerides, or waist circumference. The participants were cross-classified at baseline based on their metabolic health and obesity. In addition, the relationship between atherosclerosis and transitions in metabolic health status based on 4733 participants from baseline to the second survey after 2years was considered. The relationship between metabolic health status and the risk of transition to Carotid atherosclerosis (CA) was assessed using logistic regression and Cox proportional hazards regression analyses. In this study, the mean age of the participants was 60.7 years (standard deviation [SD], 10.91), 53.0% were female, and 51.2% had CA. As compared with metabolically healthy normal weight (MHN), those with MHO phenotype (odd ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.21), metabolically unhealthy normal weight (OR 1.27, 95% CI 1.19-1.35), metabolically unhealthy overweight (OR 1.41, 95% CI 1.33-1.48), and metabolically unhealthy obese (OR 1.54, 95% CI 1.44-1.64) had higher risk for CA. However, during the follow-up of 2years, almost 33% of the participants transitioned to a metabolically unhealthy status. As compared with stable healthy normal weight, transition from metabolically healthy to unhealthy status (hazard ratios [HR] 1.21, 95% [CI] 1.02-1.43) and stable metabolically unhealthy overweight or obesity (MUOO) (HR 1.32, 95% CI 1.17-1.48) were associated with higher risk of CA. In the community population, obesity remains a risk factor for CA despite metabolic health. However, the risks were highest for metabolically unhealthy status across all BMI categories. A large proportion of metabolically healthy overweight or participants with obesity converts to an unhealthy phenotype over time, which is associated with an increased risk of CA.

Association of metabolic health and obesity with coronary heart disease in adult cancer survivors.

The metabolically healthy obese (MHO) phenotype is associated with an increased risk of coronary heart disease (CHD) in the general population. However, association of metabolic health and obesity phenotypes with CHD risk in adult cancer survivors remains unclear. We aimed to investigate the associations between different metabolic health and obesity phenotypes with incident CHD in adult cancer survivors. We used National Health Insurance Service (NHIS) to identify a cohort of 173,951 adult cancer survivors aged more than 20 years free of cardiovascular complications. Metabolically healthy nonobese (MHN), MHO, metabolically unhealthy nonobese (MUN), metabolically unhealthy obese (MUO) phenotypes were created using as at least three out of five metabolic health criteria along with obesity (body mass index ≥ 25.0 kg/m2). We used Cox proportional hazards model to assess CHD risk in each metabolic health and obesity phenotypes. During 1,376,050 person-years of follow-up, adult cancer survivors with MHO phenotype had a significantly higher risk of CHD (hazard ratio [HR] = 1.52; 95% confidence intervals [CI]: 1.41 to 1.65) as compared to those without obesity and metabolic abnormalities. MUN (HR = 1.81; 95% CI: 1.59 to 2.06) and MUO (HR = 1.92; 95% CI: 1.72 to 2.15) phenotypes were also associated with an increased risk of CHD among adult cancer survivors. Adult cancer survivors with MHO phenotype had a higher risk of CHD than those who are MHN. Metabolic health status and obesity were jointly associated with CHD risk in adult cancer survivors.

MHO or MUO? White adipose tissue remodeling.

In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti-inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro-inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice.

Relationship of Mitochondrial DNA Oxidation and Content with Metabolic Syndrome and Cardiovascular Risk in Obesity Phenotypes.

Obesity, chronic inflammation, and oxidative stress can influence mitochondrial DNA (mtDNA) content. Our objective was to evaluate the oxidation level and content of mtDNA and its relationship with metabolic parameters in metabolically healthy obese (MHO) compared to metabolically unhealthy obese (MUO) and normal weight (NW) controls. We studied 94 NW, 95 MHO, and 97 MUO individuals between 18 and 80 years old. Relative mtDNA content and mtDNA oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method of real-time PCR. One-way ANOVA and Tukey test were used to compare biochemical, clinical, and anthropometric characteristics, as well as mtDNA content and 8-OxoG. A progressive decrease in mtDNA content was observed between NW, MHO, and MUO with significant differences in MUO vs. NW (p: 0.04). An increase in 8-OxoG was observed in MUO patients compared to the other groups (MUO vs. MHO p: 0.01; MUO vs. NW p: 0.04). mtDNA content was directly correlated with HDL-c (p < 0.01) and inversely with waist circumference (p: 0.01) and LDL-c (p: 0.05). mtDNA content decreased, and the oxidation level increased concomitantly with the presence of obesity, the number of MS components, higher coronary risk, and insulin resistance parameters. MHO presented a similar mtDNA oxidation level to NW and mtDNA content to the MUO, placing the MHO individuals as having an intermediate phenotype. Changes in mtDNA content and oxidation were correlated to the lipid profile related to obesity and/or MS presence, probably associated with oxidative stress and chronic low-grade inflammation.

Serum selenium accelerates the development of metabolic disorders in a metabolically healthy obese U.S. population: a retrospective cross-sectional analysis of a population-based study from the NHANES (2011-2018).

Obesity represents a significant risk factor for the development of metabolic abnormalities. However, it is not inevitable that all individuals with obesity will develop these disorders. Selenium has been demonstrated to play a role in maintaining metabolic homeostasis in vivo, with the ability to regulate relevant signaling pathways involved in glucose and lipid metabolism processes. Previous studies have indicated that selenium concentrations in obese individuals are higher than those reported in the general population. These findings the question of whether altered selenium concentrations may act as important triggers for accelerating metabolic imbalances in the obese population. The aim of this study was to examine the potential correlation between serum selenium concentrations and the risk of developing metabolic abnormalities in individuals with obesity. The present study included 6,125 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) who were aged between 20 and 80 years, with a body mass index (BMI) of 30 kg/m2 or greater, and met the inclusion and exclusion criteria. Weighted generalized linear regression analyses were conducted to evaluate the associations between serum selenium concentrations and the conversion of metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO). A generalized additive model (GAM) and a two-piecewise linear regression model were employed to investigate the saturation threshold effect between selenium and MUO. The correlation between different selenium concentration intervals and metabolic diseases was evaluated by categorizing selenium concentrations according to the saturation threshold. Furthermore, this study investigated the correlation between serum selenium and lipid concentrations in obese females and between serum selenium and blood pressure in obese males. The weighted prevalence of MUO in the study population was 48.35%. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of MUO increased by 44% for every 1 µM increase (approximately 78.74 µg) in the serum selenium concentration (weighted OR=1.44; 95% CI=1.09 - 1.91; P=0.018). Second, GAM analysis and saturation threshold analyses revealed an inverted U-shaped relationship between serum selenium and metabolic abnormalities in males, with a corresponding inflection point (K) of 2.82 µM. When the serum selenium concentration was below the K-value, the effects of serum selenium were mainly on blood pressure, especially diastolic blood pressure (DBP) (weighted β: 3.34; 95% CI= 0.25 - 6.44; P=0.038). Conversely, the correlation between the serum selenium concentrations and metabolic homeostasis imbalance in females was linear. When the selenium concentration exceeded 2.12 µM, the increase in selenium content was accompanied by increases in total cholesterol (TC, weighted β=0.54, 95% CI=0.32 - 0.76; P=0.000) and triglyceride (TG, weighted β=0.51, 95% CI=0.27 - 0.75; P=0.000) concentrations. The findings of our study indicate that selenium supplementation strategies for individuals with obesity should be tailored to the sex of the individual. In females, serum selenium concentration above the saturation threshold primarily facilitates the transition from MHO to MUO by influencing alterations in serum lipid metabolism. Maintaining selenium concentrations below the threshold levels is highly important for preventing the conversion of MHO to MUO. In males, serum selenium concentrations above the threshold were found to be effective in preventing an elevation in blood pressure, particularly in improving systolic blood pressure (SBP). Nevertheless, serum selenium concentrations below the threshold are linked to an increased risk of hypertension in obese individuals, particularly those with elevated diastolic blood pressure (DBP). Further research is needed to elucidate the optimal serum selenium concentration that exerts deleterious effects on blood pressure.

Tupaia belangeri (Wagner, 1841), a Northern Treeshrew is an Animal Model of Metabolic Healthy Obesity

Tupaia belangeri (Wagner, 1841), a Northern Treeshrew is an Animal Model of Metabolic Healthy Obesity

Exploring metabolically healthy obesity: prevalence, characteristics, and cardiovascular risk in the Iranian population based on the STEPS 2021.

Regarding the rapidly increasing prevalence of obesity throughout the globe, it remains a serious public health concern. A subgroup of obesity that does not meet metabolic syndrome criteria is called metabolically healthy obesity (MHO). However, whether the MHO phenotype increases cardiovascular disease (CVD) risk is controversial. This study aimed to evaluate the prevalence of MHO and its 10-year CVD risk in Iranian populations. Based on the STEPS 2021 project in Iran, we collected data on 18119 Iranians 25 years and older from all 31 provinces after applying many statistical factors. Using the Framingham score, we evaluated the 10-year cardiovascular risk associated with the various MHO definition criteria for Iranian populations. The prevalence of MHO was 6.42% (5.93-6.91) at the national level according to the AHA-NHLBI definition, and 23.29% of obese women and 24.55% of obese men were classified as MHOs. Moreover, the MHO group was younger than the metabolically unhealthy obesity (MUO) group based on all definitions (p < 0.001). The odds ratio of MUO individuals being classified as high-risk individuals by the Framingham criteria for CVD was significantly higher than that of MHO individuals by all definitions, with a crude odds ratio of 3.55:1 based on AHA-NHLBI definition. This study reveals a significant prevalence of MHO in the Iranian population, with approximately 25% of obese individuals classified as MHO. While MHO is associated with a lower risk of cardiovascular disease compared to MUO, MHO carries the potential for transitioning to an unhealthy state. The online version contains supplementary material available at 10.1007/s40200-023-01364-5.

Computed tomography evaluation of skeletal muscle quality and quantity in people with morbid obesity with and without metabolic abnormality.

We investigated the differences in quantity and quality of skeletal muscle between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) individuals using abdominal CT. One hundred and seventy-two people with morbid obesity who underwent bariatric surgery and 64 healthy control individuals participated in this retrospective study. We divided the people with morbid obesity into an MHO and MUO group. In addition, nonobese metabolic healthy people were included analysis to provide reference levels. CT evaluation of muscle quantity (at the level of the third lumbar vertebra [L3]) was performed by calculating muscle anatomical cross-sectional area (CSA), which was normalized to patient height to produce skeletal muscle index (SMI). Muscle quality was assessed as skeletal muscle density (SMD), which was calculated from CT muscle attenuation. To characterize intramuscular composition, muscle attenuation was classified into three categories using Hounsfield unit (HU) thresholds: -190 HU to -30 HU for intermuscular adipose tissue (IMAT), -29 to +29 HU for low attenuation muscle (LAM), and +30 to +150 HU for normal attenuation muscle (NAM). People with morbid obesity comprised 24 (14%) MHO individuals and 148 (86%) MUO individuals. The mean age of the participants was 39.7 ± 12.5 years, and 154 (65%) participants were women. MUO individuals had a significantly greater total skeletal muscle CSA than MHO individuals in the model that adjusted for all variables. Total skeletal muscle SMI, SMD, NAM index, LAM index, and IMAT index did not differ between MHO and MUO individuals for all adjusted models. Total skeletal muscle at the L3 level was not different in muscle quantity, quality, or intramuscular composition between the MHO and MUO individuals, based on CT evaluation. MHO individuals who are considered "healthy" should be carefully monitored and can have a similar risk of metabolic complications as MUO individuals, at least based on an assessment of skeletal muscle.

Effect of SELENIUM-CONTAINING vitamin and mineral complex on women's health

Selenium protects cells and tissues at the cellular level from damage caused by oxidative stress; This is especially true for heart disease, which remains the leading cause of death worldwide. We examined 77 women with metabolically healthy obesity (MHO) during the menopausal transition (MT), and established a connection between hypoestrogenemia and psychovegetative disorders, hypersympathicotonia, and cardialgia. It has been established that the natural non-hormonal drug SELENBIO for women has a positive effect on the psychovegetative status and episodes of cardialgia during MHO in women with estrogen deficiency during the MT. The drug SELENBIO for women has a complex, versatile effect on the female body, helps normalize hormonal levels and ovarian function, neutralizes clinical manifestations, has a general strengthening and immunomodulatory effect, and, thanks to its antioxidant effect at the cellular level, slows down the aging process. All components of the drug are physiologically close to the human body and do not disrupt the natural processes occurring in it. The drug SELENBIO for women is highly effective with low toxicity, has a wide spectrum of action, and has a complex harmonizing effect on the body.

The mediatory role of inflammatory markers on the relationship between the NOVA classification system and obesity phenotypes among obese and overweight adult women: a cross-sectional study.

Diet and inflammation both play important roles in the occurrence of obesity. We aimed to investigate the role of inflammation in the development of both metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) individuals. This cross-sectional study included 221 overweight and obese women aged 18-56 years. The study assessed the metabolic health phenotypes of the participants using the Karelis criterion score. Additionally, dietary intakes were evaluated using a 147-item semi-quantitative questionnaire and the NOVA classification system (comprising 37 food groups and beverages). The study also collected and analyzed the blood parameters, as well as biochemical and anthropometric indices, for all participants. Among the women included in the study, 22.9% had MHO phenotypes but 77.1% had MUHO phenotypes. A significant association between the third quartile of the NOVA classification system and the increased likelihood of having the MUHO phenotype was observed (OR = 1.40, 95% CI = 1.09-4.92, p = 0.04). Regarding the potential role of inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) (p = 0.84), transforming growth factor-β (TGF-β) (p = 0.50), monocyte chemoattractant protein-1 (MCP-1) (p = 0.49), plasminogen activator inhibitor-1 (PAI-1) (p = 0.97), and homeostatic model assessment for insulin resistance (HOMA-IR) (p = 0.92) were found to be mediators. We observed a significant positive association between ultra-processed food (UPF) consumption and the MUHO phenotype in overweight and obese women. This association appeared to be mediated by some inflammatory markers, such as hs-CRP, TGF-β, MCP-1, PAI-1, and HOMA-IR. Additional studies are needed to validate these findings.

Single Nucleotide Variants of the VDR Gene and Cardiometabolic Risk in Obesity

BackgroundVitamin D deficiency is associated with impaired glucose tolerance, insulin resistance, metabolic syndrome, and an increased risk of developing type 2 diabetes. Aim: to define the contribution of single nucleotide variants (SNV) of the vitamin D receptor (VDR) gene to the development of metabolically unhealthy obesity (MUO) in children. Materials and Methods200 obese children aged 6-18 years were examined. The main group (n=118) was represented by children with MUO. The control group (n=82) consolidated of children with metabolically healthy obesity (MHO). Whole genome sequencing (CeGat) was performed in 31 children of the main and 21 children of the control group. The level of serum 25-hydroxyvitamin D (Synevo) was measured in all children. Verification of results: calculation of Spearman's correlation coefficient (r) and p-value for each variable. ResultsFive SNVs of the VDR gene were identified: rs2228570 (1 DNA copy number variation (CNV): c.2T>C in 94.23%; rs731236 (2 CNVs: c.11056T>C, c.1206T>C in 65.38%); rs10783218 (2 CNV: c.296+8C>T, c.146+8C>T in 7.69%); rs2228572 (2 CNV: c.57C>T, c.207C>T in 1.92%); rs12721365 (2 CNV: c. 1059C>T, c.909C>T in 1.92% of patients). A correlation between SNV VDR and MUO was observed in the following genotypes: AA rs12721365 (r=0.21), AA rs2228572 (r=0.21) and GG rs2228570 (r= -0.31), p<0.05. A correlation between vitamin D deficiency and SNV VDR was noted for the following genotypes: AA genotype rs12721365 (r= 0.41), AA genotype rs2228572 (r= 0.38) and GG rs 2228570 (r= -0.27), p<0.05. ConclusionsThe development of cardiometabolic risk and vitamin D deficiency in obese children is associated with the presence of AA/AG genotypes SNV VDR rs2228570, rs12721365, rs2228572.

The effects of weight loss and improved metabolic health status on the risk of non-alcoholic fatty liver disease—results from a prospective cohort in China

BackgroundThe impact of weight loss and/or improved metabolic status on the risk of non-alcoholic fatty liver disease (NAFLD) has yet to be determined.MethodsA total of 35,322 participants without NAFLD were followed. NAFLD risk was compared between consistently metabolically healthy non-obese (MHNO) and non-MHNO who lost weight to become non-obese and/or improved their metabolic health, using Cox proportional hazards and logistic regression models.ResultsFollowing 148,186 person-years, 8,409 participants had onset NAFLD, with an incidence rate of 56.75 (95% CI: 55.57, 57.94) per 1,000 person-years. Metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), and metabolically unhealthy non-obese (MUNO) at baseline were associated with increased NAFLD risk, with hazard ratios of 4.48 (95%CI:4.24, 4.73), 8.85 (95%CI:7.95, 9.84), and 10.70 (95%CI:9.73, 11.78). Weight loss and/or metabolic status improvements could significantly reduce NAFLD risk by 79.46 to 41.46%. Specifically, after weight loss from MHO to MHNO, the reduction in NAFLD risk [OR decreased from 12.01 (95%CI:9.40, 15.35) to 4.14 (95%CI:3.08, 5.57)] was greater than that of the MUNO subgroup whose metabolic status improved to MHNO [OR decreased from 5.53 (95%CI:5.15, 5.94) to 2.71 (95%CI:2.50, 3.93)]. In the MUO subgroup, the group with the greatest risk reduction of NAFLD was the weight and metabolic state both improvement group [MUO to MHNO, OR decreased from 22.74 (95%CI:17.61, 29.37) to 4.67 (95%CI:3.05, 7.16)], followed by the weight loss only group [MUO to MUNO, OR decreased to 6.83 (95%CI:4.87, 9.57)], and finally the group with the least and insignificant risk reduction was the metabolic state improvement group [MUO to MHO, OR decreased to 13.38 (95%CI:9.17,19.53)]. NAFLD risk was negatively correlated with the duration of improvement (p &amp;lt; 0.001).ConclusionIndividuals with non-MHNO were more likely to develop NAFLD than those with consistent MHNO, but metabolic improvements and weight loss can alleviate the risk. Their NAFLD risk was negatively correlated with improvement duration. However, it remained higher than in individuals with consistent MHNO at an average follow-up of 4.2 years.

The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes-New Perspectives.

Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.

Homeostatic model assessment of β-cell function may be an emerging predictor of bone resorption in metabolically unhealthy obesity

Objectives: The aim of this study is to compare three distinct bone markers in metabolically healthy and unhealthy obese and non-obese subjects, according to various metabolic health criteria.&#x0D; Methods: The study enrolled a total of 35 subjects, including 11 healthy normal-weight and 23 obese subjects. Based on HOMA-Beta, all participants were divided into three groups: normal weight (HOM-Beta&lt;100%, n=11), obese (HOMA-Beta &lt;100%, n=12), and obese (HOMA-Beta &gt;100%, n=12). The serum levels of osteocalcin, procollagen I amino-terminal propeptide (P1NP), and beta-cross Laps as bone turnover markers, as well as serum levels of 25 (OH) vitamin D3, and PTH were analyzed.&#x0D; Results: Significant differences were observed in BMI, age, 25(OH)D3, FBS, Insulin, HOMAIR, and HOMA-Beta among the groups. Analysis of bone markers revealed that the serum levels of Beta-cross Laps, P1NP, and osteocalcin were significantly different among all studied groups categorized by the HOMA-Beta model. In this context, circulating levels of osteocalcin and Betacross Laps in the normal weight group (HOMA-Beta&lt;100%) were significantly higher than the obese group (HOMA-Beta &lt;100%). In obese patients with HOMA-Beta &lt;100%, Beta-cross Laps and P1NP levels were lower compared to the obese group with HOMA-Beta &gt;100%.&#x0D; Conclusion: The data suggests that HOMA-Beta, as an index of β-cell function, can be used in part of metabolically healthy obese (MHO) criteria and bone remodeling is altered in the context of metabolically healthy obesity.

Integrated genetic and epigenetic analyses uncovered GLP1R association with metabolically healthy obesity.

Both genetic and epigenetic variations of GLP1R influence the development and progression of obesity. However, the underlying mechanism remains elusive. This study aims to explore the mediation roles of obesity-related methylation sites in GLP1R gene variants-obesity association. A total of 300 Chinese adult participants were included in this study and classified into two groups: 180 metabolically healthy obesity (MHO) cases and 120 metabolically healthy normal-weight (MHNW) controls. Questionnaire investigation, physical measurement and laboratory examination were assessed in all participants. 18 single nucleotide polymorphisms (SNPs) and 31 CpG sites were selected for genotype and methylation assays. Causal inference test (CIT) was performed to evaluate the associations between GLP1R genetic variation, DNA methylation and MHO. The study found that rs4714211 polymorphism of GLP1R gene was significantly associated with MHO. Additionally, methylation sites in the intronic region of GLP1R (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 12.13; GLP1R-68-CpG 17; GLP1R-68-CpG 21) were associated with MHO, and two of these methylation sites (GLP1R-68-CpG 7.8.9; GLP1R-68-CpG 17) partially mediated the association between genotypes and MHO. Not only the gene polymorphism, but also the DNA methylation of GLP1R was associated with MHO. Epigenetic changes in the methylome may in part explain the relationship between genetic variants and MHO.

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. Obesity (body mass index ≥ 30kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. Analyses with exposures measured < 60, 60 to < 70, and ≥ 70years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2years respectively. In analyses of individual components, obesity before 60years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70years or ≥ 70years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70years.

Abstract 16025: Impact of COVID-19 on Major Adverse Cardiovascular and Cerebrovascular Events in Metabolically Healthy Obese (MHO) Individuals: A National Inpatient Sample Analysis, 2020

Background: The obesity paradox is a phenomenon observed in certain chronic diseases, particularly cardiovascular diseases, where individuals with obesity have better outcomes compared to those of normal weight. We aimed to study how COVID-19 affects MACCE results in metabolically healthy obese (MHO) individuals who have a BMI &gt;30. Methods: Using the National Inpatient Sample (2020) and appropriate ICD-10-CM codes, we identified adult hospitalizations with COVID-19 and grouped them into two cohorts with and without obesity (MHO+ and MHO-, omitting hypertension, diabetes, and hyperlipidemia). MACCE (all-cause inpatient mortality, cardiac arrest, including ventricular fibrillation, and stroke) in COVID-19-related hospitalizations was the primary outcome. Results: 84,145 (21.9%) of 397,040 COVID-19 hospitalizations were MHO+. The MHO+ group was younger (median 43 vs 52 years), female (56.9% vs. 49.4%), black (19.4% vs 15.1%), Hispanic (35.2% vs 30.5%), and Native American (1.5% vs 1.2%) (p&lt;0.001). Tobacco use disorder, past PCI, prior VTE, depression, chronic pulmonary disease, hypothyroidism, and other thyroid problems were more common in MHO+ patients (p&lt;0.05). MHO+ patients were discharged routinely (76% vs. 66.7%) but stayed longer (5 days vs 4 days). After correcting for baseline variables, the MHO+ cohort had a lower rate of MACCE than the MHO- cohort (8% vs. 11.3%, OR 0.81, 95CI 0.74-0.89, p&lt;0.001), and lower all-cause mortality (6.6 % vs 9.4%) compared to the MHO- cohort. On subgroup analysis, females had lower odds (aOR 0.79) than males (aOR 0.82), older individuals ≥65 years old had lower odds (aOR 0.71) vs 45-64 (aOR 0.79), and race- wise comparison, whites had lower odds of MACCE events (aOR 0.76). Conclusions: MHO+ patients had lower odds of MACCE events. The MHO group was younger, suggesting higher cardiorespiratory fitness, which could explain the obesity paradox and reduced odds of MACCE outcomes.

Abstract 13509: Cardiovascular Outcomes in Metabolically Healthy Obese Asian-American Population Insights From a National Inpatient Sample

Background: Cardio-metabolic risk factors usually predict major adverse cardio and cerebrovascular events (MACCE). However, outcomes in young metabolically healthy obese (MHO) Asian Americans (AA) have not been studied yet. Methods: Using the National Inpatient Sample (2019), we identified hospitalizations among young obese AA [aged 18-44] to obtain propensity-matched MHO+ and MHO- cohorts. Multivariable regression analyses were performed after controlling baseline demographic and comorbid variables to assess the risk of MACCE, including all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke. Multivariable predictors of MACCE were also analyzed. P &lt;0.05 was statistically significant. Results: Of total 327,065 young AA hospitalizations, 25,470 were obese. Propensity-matched cohorts of MHO+ (n=14,200) and MHO-(n=14,200) were comparable for demographics (Median age 32 years, females 85.9% vs 84.8%). After adjusting for baseline demographics and comorbidities, the odds of MACCE (aOR 0.98, 95%CI 0.70-1.37, p=0.886) were higher, and ACM (aOR 1.26, 95CI% 0.4-3.99, p=0.690) was lower in MHO+ compared to MHO- group however, it was not statistically significant. MHO patients also had higher rates for MACCE among males (OR 10.18, 95%Cl 3.39-30.53, p &lt;0.001), drug abusers (OR 2.87, 95%Cl 1.05-7.86, p=0.04), cancer (OR 9.70, 95%Cl 2.14-44.01, p =0.003) and congenital circulatory anomalies (OR 21.77, 95Cl 4.07-116.60, p &lt;0.001). Conclusion: Obese AA population without cardiometabolic risk factors define a subgroup of at-risk population with males, drug abusers, cancers, and congenital abnormalities pose an increased risk of adverse cardio and cerebrovascular events. Targeted interventions, early risk stratification, and preventive measures are warranted in these populations.

Abstract 15895: Bariatric Surgery and Subclinical Myocardial Injury

Background: Obesity is linked with subclinical myocardial injury, even in those with metabolically healthy obesity (MHO). There is limited data on the impact of weight loss via bariatric surgery on myocardial injury, particularly at different levels of metabolic health. Methods: We prospectively evaluated 294 Geisinger Obesity Institute Registry participants undergoing bariatric surgery and 294 controls matched on age, sex, body mass index (BMI;± 5kg/m 2 ) and diabetes status. High-sensitivity cardiac troponin I (hs-cTnI) was measured pre-operatively and at 6-18 months post-operatively in bariatric surgery patients, and at similar intervals in controls. Using linear regression, we examined the association of bariatric surgery with change in log transformed hs-cTnI (ln-hs-cTnI), stratified by metabolic health status: MHO (metabolic syndrome absent), metabolically unhealthy obesity (MUO; metabolic syndrome present), and MUO with diabetes. We used logistic regression to characterize the association of weight change (modeled as a restricted cubic spline) with the OR of transitioning from detectable to undetectable hs-cTnI (limit of detection 1.2ng/L). Results: The mean age was 45 years with 83% female, 97% White, and mean BMI of 47 kg/m 2 . Baseline characteristics of bariatric surgery patients and controls were similar. Bariatric surgery was associated with significant reduction in ln-hs-cTnI compared with controls in each stratum of metabolic health (P for interaction = 0.63; Panel A). Bariatric surgery was associated with an OR of 9.02 (95% CI 3.52-23.10) for transitioning from detectable to undetectable hs-cTnI, with a dose response association between weight loss and higher odds of developing undetectable hs-cTnI (Panel B). Conclusion: Bariatric surgery induced weight loss mitigates subclinical myocardial injury in graded fashion and across metabolic health strata, which may reflect one mechanism for the cardioprotective benefits of weight loss.

Abstract 16787: Impact of Metabolic Healthy Obesity on Cardiovascular Outcomes of Hospitalized Postmenopausal Women (Age&gt;55 Years) and Associated Disparities: A Population-Based Analysis

Introduction: Metabolically healthy obesity's (MHO) impact on cardiovascular outcomes is debated. However, MHO's impact on cardiovascular outcomes in postmenopausal women is unexplored. Our study explored MHO's prevalence and correlation with in-hospital major adverse cardiac and cerebrovascular events (MACCE) in postmenopausal women. Methods: Data was analyzed from National Inpatient Sample 2020 for admissions of postmenopausal women (&gt;age 55 years) with and without obesity. Metabolically healthy patients were identified by excluding diabetes, hypertension, and hyperlipidemia using Elixhauser comorbidity software. After propensity score matching (PSM) patients with MHO and non-MHO for age, we performed a multivariable regression analysis for in-hospital MACCE. Also, using tests of model effects, we determined predictors of MACCE in postmenopausal women with MHO. Results: In 2020, 1304185 metabolically healthy postmenopausal women over age 55 years were admitted; 1155935 (88.6%) had no MHO, and 148250 (11.4%) had MHO. However, after PSM for age, there were 148250 in each cohort. In MHO cohort, median age was 65 years, 78.6% were white, 8.1% were African-American, and 28.2% were from lowermost income quartile. Most common comorbidities in MHO cohort were chronic pulmonary disease (29.2%), hypothyroidism (20.7%), and tobacco use disorder (23.9%). We observed a statistically significant difference in overall MACCE [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.01-1.16, p=0.028] among MHO and non-MHO cohorts, especially in patients from African-American ethnicity (OR 1.23, 95% CI 1.01-1.49, p=0.035) and lowermost income quartile (OR 1.24, 95% CI 1.06-1.44, p= 0.007). However, no significant all-cause mortality was observed (OR 1.02, 95% CI 0.94-1.12, p=0.621). Several predictors of MACCE in postmenopausal women with MHO were observed, with non-elective admission being the strongest (OR 7.38, 95% CI 5.91-9.22, p&lt;0.001). Conclusion: This large population-based analysis revealed that postmenopausal patients with MHO are at risk of MACCE, particularly those from African-American ethnicity and lowermost income quartile. Larger prospective studies are needed to "demystify" the controversial MHO in cardiovascular diseases.