this study aims to determine the prevalence and determinants of metabolically healthy obesity (MHO) and metabolically healthy status (MHS) within a large Iranian population.

This cross-sectional study involved 10,134 participants from the Fasa Adult Cohort Study (FACS) in southern Iran. Following the extraction of metabolic, demographic, and socioeconomic variables, prevalence rates were estimated. Logistic regression analysis was conducted using SPSS 22 to examine the relationship between risk factors.

Among all participants, 19.9% (32.7% in men) exhibited metabolically healthy status (MHS), while 31.4% (37.5% in men) were classified as metabolically healthy obese (MHO). The likelihood of MHO was found to be 18% higher in illiterate individuals compared to their literate counterparts. Additionally, for each 1 cm increase in waist circumference, the probability of MHO increased by 5%, while a 1-year increase in age raised the probability by 1.7%, and a 1 MET increase in physical activity reduced the probability by 1.3%. Furthermore, the likelihood of having MHS was 2.4 times greater in women than in men. Employed individuals had a 17% lower probability of MHS compared to unemployed individuals. For every 1 MET increase in physical activity, the probability of MHS decreased by 0.9%, whereas a 1-year increase in age and a 1 cm increase in waist circumference increased the probability by 1.7% and 12%, respectively.

It seems that MHS and MHO is relatively high in studied population and although their multifactorial nature was determined, at the same time, in order to evaluate the changes, it is necessary to pay serious attention to longitudinal monitoring.

The online version contains supplementary material available at 10.1007/s40200-024-01555-8.

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologs in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.

Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites. Lipidomics analysis revealed a strategic adaptive reduction in membrane lipids and an increase in storage lipids in MTCH2 knockout cells. Importantly, MTCH2 knockout cells showed an increase in mitochondrial oxidative function, which may explain the higher energy demand. Interestingly, this imbalance in energy metabolism and reductive potential triggered by MTCH2-deletion prevents NIH3T3L1 preadipocytes from differentiating into mature adipocytes, an energy consuming reductive biosynthetic process. In summary, the loss of MTCH2 leads to increased mitochondrial oxidative activity and energy demand, creating a catabolic and oxidative environment that fails to fuel the anabolic processes required for lipid accumulation and adipocyte differentiation.

Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin-angiotensin-aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes.

We studied 1430 adults on controlled dietary sodium. Individuals in the MHOO group had BMI ≥ 25 kg/m2 without comorbidities (e.g., diabetes, dyslipidemia, hypertension, CVD), whereas individuals in the MUOO group had BMI ≥ 25 kg/m2 and at least one comorbidity. The control group included healthy individuals (BMI 18.5-24.9 kg/m2).

BMI was similar between the MHOO (28.9 kg/m2) and MUOO groups (29.3 kg/m2; p = 0.317). On liberal sodium, the MUOO group had activated RAAS compared with the MHOO group, including higher plasma aldosterone concentration (mean [SD], 1.11 [0.48] ng/dL; p = 0.020), plasma angiotensin II levels (4.11 [2.0] pg/mL; p = 0.040), and percentage of individuals with plasma renin activity ≥ 1.0 ng/mL/h (+3.6%; p = 0.017). The MUOO group had higher SSBP than the MHOO group (6.0 [1.9] mm Hg; p = 0.002). Applying a zero-to-six-point metabolic health score found that a worse score was associated with higher measurements of RAAS activity and SSBP (p < 0.001).

Compared to the MHOO group, the MUOO group was characterized by an increase in the following two CVD risk factors: higher RAAS activity and SSBP on controlled sodium diets. Therapeutic interventions targeting the effects of angiotensin II and/or aldosterone may offer cardiometabolic protection for individuals with the MUOO phenotype.

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologous in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.

To explore whether metabolically healthy overweight (MHOW) and/or metabolically healthy obesity (MHO) increase hyperglycaemia risk in a Chinese population with a broad age range.

Retrospective cohort study.

Secondary analysis of data from the DATADRYAD database, comprising health check records of participants from 32 regions and 11 cities in China between 2010 and 2016.

A total of 47 391 metabolically healthy participants with none of the metabolic abnormalities were selected.

Hyperglycaemia includes incident diabetes and impaired fasting glucose (IFG). Diabetes was diagnosed with fasting blood glucose ≥7.0 mmol/L and typical clinical symptoms and/or on self-report during follow-up. The fasting plasma glucose level of IFG was from 5.6 to 6.9 mmol/L.

With an average follow-up of 3.06 years, 5274 participants (11.13%) developed hyperglycaemia over 144 804 person-years, with an incidence rate of 36.42 per 1000 person-years. Adjusted model revealed a higher risk of incident hyperglycaemia in the MHOW group (HR=1.23, 95% CIs 1.16 to 1.30) and the MHO group (HR=1.49, 95% CI 1.33 to 1.67) compared with the metabolically healthy normal weight group. With 1 unit increase of body mass index, the risk of hyperglycaemia increased by 6% (HR=1.06, 95% CI 1.04 to 1.07). The stratified analyses and interaction tests showed the robustness of the association, and there was a stronger association in women (p for interaction<0.001).

The MHOW and MHO phenotypes were positively associated with a higher risk of hyperglycaemia in this population, and the association was particularly stronger in women.

The concept of metabolically healthy obesity (MHO) has not been studied in type 1 diabetes (T1D). By analysing datasets from the DCCT/EDIC study, we compared the development of diabetic complications by obesity and metabolic health over 30 years of follow up.

Insulin resistance was calculated by estimated glucose disposal rate (eGDR). The participants (n = 1127) were then divided into four groups based on time-weighted mean body mass index and mean eGDR: metabolically healthy non-obesity (MHN, n = 874), metabolically unhealthy non-obesity (MUN, n = 66), MHO (n = 146) and metabolically unhealthy obesity (MUO, n = 41). Diabetic complications and cardiovascular events were compared across the four groups.

MUO and MUN groups had significantly higher risk for peripheral neuropathy (p = 0.001 in MUO and p < 0.001 in MUN vs. MHN), cardiac autonomic neuropathy (p < 0.001 in both MUO and MUN vs. MHN), retinopathy (p = 0.001 in MUO and p < 0.001 in MUN vs. MHN) and microalbuminuria (p < 0.001 in both MUO and MUN vs. MHN) than MHN group. Moreover, MUO and MUN groups had significantly higher risks (HR [95%CI]) in any cardiovascular events (2.78 [1.51-5.11] and 1.88 [1.05-3.36]) and major atherosclerotic cardiovascular events (2.72 [1.16-6.37] and 2.31 [1.05-5.10]) compared to MHN group. However, the risk of these complications and cardiovascular events (except peripheral neuropathy and cardiac autonomic neuropathy) in MHO group was not different from that in MHN group.

This study highlights the importance of metabolic health represented by insulin resistance in the development of diabetic complications and cardiovascular events in T1D beyond their weight status.

Obesity is a global public health issue, with limited epidemiologic studies on the relationship and mechanisms between organophosphate flame retardants (OPFRs) and metabolic obesity phenotypes (MOPs). We aimed to explore the link between OPFRs metabolite (m-OPFRs) and MOPs using a combined epidemiologic and bioinformatic approach. We used cross-sectional survey data from the U.S. National Health and Nutrition Examination Survey (2011-2018) to analyze the relationship between m-OPFRs and metabolic health obesity (MHO), as well as metabolic unhealthy obesity (MUO). The dataset encompasses eligible adults to assess the impact of individual, mixed, and mediated effects on the outcome variables through multivariate logistic regression, Bayesian kernel machine regression (BKMR), and mediation analysis. Multiple logistic regression models, stratified by tertiles of exposure showed that bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) levels in the body significantly increased the risk of MHO, with OR and 95%CI of 1.454 (1.082, 1.953) for the second tertile (T2) and 1.598 (1.126, 2.268) for the third tertile (T3), compared to the first tertile (T1). Increased levels of BDCIPP in T3 (1.452(1.013, 2.081)) are associated with MUO, compared to T1. Mixed m-OPFRs and MHO risk in BMKR were positively correlated, with BDCIPP being the primary contributor. We found that the serum uric acid (SUA) and white blood cell count (WBC) indicators significantly mediated the association between BDCIPP and MHO (P < 0.05). Our study suggests that OPFRs, either individual or mixed, are associated with two distinct MOPs, with oxidative stress playing an important role. In addition, in silico analysis was used to screen for shared genes, and eight shared genes and eleven biological pathways identified during the screening process were used to construct the adverse outcome pathway, which suggests that exposure to OPFRs may activate the peroxisome proliferator-activated receptor (PPAR) pathway, thereby increasing the risk of obesity. Further studies are needed to validate our findings.

The relationship between serum calcium and occurrence of MHO (metabolically healthy obesity) and MUNO (metabolically unhealthy non-obesity) remains unclear, and distinguishing these two phenotypes is difficult within primary healthcare units. This study explores that relationship.

This survey included 28590 adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Obesity phenotypes were categorized based on BMI and presence or absence of metabolic syndrome components. Weighted multivariate logistic regression analyses were used to assess the association between serum calcium levels and the obesity phenotype. Restricted cubic spline analysis characterized dose-response relationships, and stratified analyses explored these relationships across sociodemographic and lifestyle factors.

The overall prevalence of MHO and MUNO were 2.6% and 46.6%, respectively. After adjusting for covariates, serum calcium exhibited a negative association with MHO [OR (95%): 0.49 (0.36,0.67), p < 0.001], while exhibiting a positive association with MUNO [OR (95%): 1.48 (1.26,1.84), p < 0.001]. Additionally, we found a non-linear association between serum calcium levels and the incidences of MHO and MUNO. Stratified analyses demonstrated a strong negative correlation between serum calcium levels and MHO occurrence across various subgroups. There was no significant interaction between calcium and stratified variables except sex; the association between calcium and the occurrence of MHO was remarkable in female patients. Meanwhile, the predictive ability of serum calcium level for the occurrence of MUNO among all patients was consistent across various subgroups. There was a significant interaction between calcium level and stratified variables based on age, sex, race, and smoking status; the association was remarkable in older (≥ 40 years old), white, none or less smoking, and female patients.

A significant correlation was identified between serum calcium levels and MHO or MUNO. The findings suggest that serum calcium levels may serve as an indicator for more accurate assessment and diagnosis of MUNO and MHO, especially among individuals with abdominal obesity.

One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity.

Patients with BMI ≥ 30 kg/m2 and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels.

Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage.

The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health.

Most patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear.

The aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype. Secondary objective was weight loss to MH.

University Hospital, Germany.

Patients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at our obesity surgery center were included in this retrospective study. Liver biopsy was taken and evaluated for presence of NAFLD/NASH. For diagnosis of MH, blood pressure and laboratory values referring to the MetS were assessed preoperatively and at 3, 6, 12, and 24 months' postoperatively.

One hundred thirty-three patients (73% female) with a mean body mass index of 52.0 kg/m2 and mean age of 43 years were included in this study. A total of 55.6% underwent RYGB and 44.4% underwent SG. NAFLD was found in 51.1% of patients and NASH in 33.8%. All patients were diagnosed MUO at baseline. Postoperatively, 38.3% patients (n = 51) switched to a MH condition. Mean time to MH was 321 days and mean excess body mass index loss to MH was 63.8%. There were no differences regarding liver health status, operative procedure, or sex.

Bariatric surgery can resolve MUO independent of liver health status, operative procedure, and sex. However, patients should be closely monitored to ensure sustainable long-term outcomes following the switch to the MH condition.

This study explored the association between ω-6 to ω-3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome in women experiencing climacteric syndrome.

The study involved 186 female participants and utilized surveys, anthropometric measurements (waist circumference, height, BMI, waist-to-height ratio), blood pressure assessments, and blood samples for lipid profile, glucose, insulin, HbA1c analysis. Serum PUFAs levels were analyzed using gas chromatography-mass spectrometry.

The study found significantly higher measurements of waist circumference, waist-to-height ratio, systolic and diastolic blood pressure in postmenopausal women with metabolic syndrome compared to the control group. In addition, the metabolic syndrome group showed significantly higher levels of fasting blood glucose, triglycerides, low-density lipoprotein cholesterol, HbA1c, insulin, triglyceride to high-density lipoprotein ratio, and total cholesterol to high-density lipoprotein ratio. Furthermore, the study also identified significant differences among premenopausal women, postmenopausal women with metabolic syndrome, and postmenopausal women without metabolic syndrome in terms of omega-3 alpha-linolenic acid, omega-3 docosahexaenoic acid, omega-6 arachidonic acid, and omega-6 to omega-3 ratio.

We observed that high ω-6 arachidonic acid and ω-6/ω-3 ratio and low ω-3 ALA and ω-3 DHA were associated with high TG and WHtR. High TG and WHtR levels in postmenopausal women are associated with increased risk of Mets.

Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment.

While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom.

This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence.

After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99-1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09-1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07-1.26), TyG-WC (HR: 1.13, 95% CI: 1.03-1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07-1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06-1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (p overall = 0.041, p non-linear = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%).

Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents.

Chronic systemic inflammation is a hallmark of obesity. This cross-sectional study aimed to investigate the association between metabolic obesity phenotypes and inflammatory markers in Korean adults (N = 21,112; mean age: 50.9 ± 16.6). Metabolic obesity phenotypes were categorized into metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO) based on body mass index and the presence of any metabolic abnormalities. High-sensitivity C-reactive protein (hs-CRP) levels were measured. Multiple linear regression was used to determine the association between obesity phenotypes and hs-CRP levels. In the male sample, compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 22.3% (95% confidence interval; CI: 14.7-30.3%), 15.8% (95% CI: 2.6-30.7%), and 12.5% (95% CI: 3.0-22.9%) increase in the hs-CRP levels, respectively. The association between metabolic obesity types and hs-CRP levels was stronger among the female sample; compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 30.2% (95% CI: 22.8-38.2%), 16.0% (95% CI: 6.5-26.4%), and 22.8% (95% CI: 13.6-32.8%) increase in the hs-CRP levels, respectively. Our findings indicate a varying profile of systemic inflammation across different metabolic obesity phenotypes.

Obesity/overweight and metabolic anomalies are known to be associated with elevated cardiovascular disease (CVD) risk. However, there is a paucity of research exploring the association between different body weights, varying metabolic statuses, and the occurrence of CVD in the Chinese population. Thus, we performed this study to explore the relation between different metabolic overweight/obesity phenotypes and the prevalence of CVD.

We analyzed data from 9075 participants in the Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) study. Participants were classified into four metabolic phenotypes based on their metabolic status and obesity/overweight status. Regression analysis was used to evaluate the relationship between CVD and different groups. Additionally, we conducted a subgroup analysis to further explore the relationship between CVD and different metabolic abnormalities.

Compared to metabolically healthy non-overweight/obesity (MHNO) individuals, both overweight/obesity and metabolic anomalies were positively associated with CVD prevalence. Among other metabolically unhealthy and overweight/obesity phenotypes, metabolically healthy overweight/obesity (MHO) generally exhibited a comparatively lower association with CVD. In the elderly, high waist circumference was significantly associated with CVD, rather than body weight. Further analysis revealed that hypertension had the strongest association with CVD.

Elderly individuals should place more emphasis on managing their waist circumference rather than only on BMI. CVD prevention should focus on both body weight management and treatment of metabolic diseases, with particular emphasis on antihypertensive therapy.

The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population.

This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models.

During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11).

MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: body mass index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 12 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33, 0.11-0.87) but increased risk in the BFP model (OR: 1.66, 1.01-2.76). The BMI model demonstrates exceptional predictive ability (AUC = 0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions: BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

Four phenotypes relate metabolism and obesity: metabolically healthy (MHO) and unhealthy (MUO) people with obesity and metabolically healthy (MHNO) and unhealthy (MUNO) people without obesity. No studies have addressed the association between these categories and lung function in the working population.

The aim was to determine the relationship of phenotypes to lung ageing as measured by lung age and its relationship to lung dysfunction.

A descriptive cross-sectional study was conducted in a working population. The outcome variable was lung function assessed by lung age. The four phenotypes of obesity and metabolic health (MHNO, MHO, MUO and MUNO) were determined using NCEP-ATP III criteria. Lung dysfunctions were classified into restrictive, obstructive, and mixed patterns.

The mean age of the participants was 43.7 years, ranging from 18 to 67 years. Of the 1860 workers, 51.3 % were women. The prevalences found were 71.4 %, 12 %, 10.6 % and 6 % for MHNO, MUO, MHO, and MUNO, respectively. MHO (β = 0.66; p = 0.591) was not associated with increased lung ageing compared with MHNO, but MUO (β = 7.1; p < 0.001) and MUNO (β = 6.6; p < 0.001) were. Concerning pulmonary dysfunctions, MUNO (OR = 1.93; p < 0.001) and MUO (OR = 2.91; p < 0.001) were found to be related to the presence of a restrictive pattern, and MUNO (OR = 2.40; p = 0.028) to the mixed pattern.

The results show that metabolic abnormalities, not obesity, are responsible for premature lung ageing and, therefore, lung function decline. In our study, having obesity without metabolic abnormality was not significantly associated with the presence of dysfunctional respiratory patterns.

This retrospective study aimed to investigate the association of initial muscular fitness (MF) with weight loss and metabolic health status in 282 children and adolescents with obesity during 3 to 4 weeks of diet- and exercise-based interventions. Metabolically healthy obesity (MHO) definitions established in 2023 and MF standards based on the 2021 Chinese children's grip strength grading were applied. The proportion of metabolically unhealthy obesity (MUO) was higher in the high MF group than in their low MF counterparts at baseline. After the intervention, neither group transitioned from MUO to MHO due to the high frequency of low HDL-C. High MF females showed a higher percentage of high systolic blood pressure (SBP) than low MF females before and after intervention. High MF males exhibited greater improvements in waist circumference, hip circumference, waist-hip ratio, triglycerides, total cholesterol, and LDL-C than low MF males. The benefits of weight loss and blood lipids obtained by males are more evident than those obtained by females under the same MF level. Thus, attention should be paid to females during weight loss regardless of MF levels. Precision therapy should prioritize the management of blood pressure and avoid excessive reduction in HDL-C levels to sustain metabolic health.

The metabolically healthy obesity (MHO) phenotype represents a complex and distinctive trait, the trends and characteristics of which remain unknown in the Saudi Arabian adult population. The present study aims to fill that gap. A combined total of 10,220 Saudi adults from 2 independent cohorts [2008-2019, N = 7,896 (2,903 males and 4,993 females), and 2021-2023, N = 2,324 (830 males and 1,494 females)] aged 19-70 years old was screened, of whom 9,631 (3,428 males and 6,203 females) were included. Anthropometric data were measured, and fasting blood samples were collected to assess glucose, lipids, adipocytokines and inflammatory markers using routine methods and commercially available assays. Obesity was defined as a body mass index (BMI) ≥30 kg/m2. Screening for MHO was done using the empiric definition proposed by Zembic and colleagues and the by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATPIII). Of the 3,949 (41.0%) participants with obesity, 33.4% (95% confidence interval, CI, 32-35) were considered MHO using the empiric definition, and 32.8% (95% CI, 31-34) using NCEP-ATPIII. The overall age and gender adjusted prevalence of MHO in the Saudi adult population was 31.6% (95% CI, 30-33) and 30.1% (29-31) by the two definitions, respectively. Females had a higher age-adjusted prevalence of MHO than males (OR = 1.22, 95% CI 1.1-1.4, p = 0.009) as per the ATPIII criteria. MHO prevalence substantially increased over time from 2008 to 2023 (p < 0.001) for both definitions. Circulating leptin levels and insulin resistance were significantly higher in the MUO group than the MHO group independent of the definition used, suggesting the presence of a more severe form of leptin resistance in the MUO group which may explain the worse cardiometabolic profile as compared to the MHO group. In summary, the study highlights the first time the characteristics and trends of the MHO phenotype among Saudi Arabian adults. The pluripotent effects of leptin and its resistance may be central to MHO's progression, or lack thereof, to the MUO phenotype, and this needs further investigation.

The impaired function of the serotonin transporter (SERT) in humans has been linked to a higher risk of obesity and type 2 diabetes, especially as people age. Consuming a "Western diet" (WD), which is high in saturated fats, cholesterol, and sugars, can induce metabolic syndrome. Previous research indicated that mice carrying a targeted inactivation of the Sert gene (knockout, KO) and fed a WD display significant metabolic disturbances and behaviors reminiscent of ADHD. These abnormalities might be mediated via a dysfunction in insulin receptor (IR) signaling, which is also associated with adult ADHD. However, the impact of Sert deficiency on IR signaling and systemic metabolic changes has not been thoroughly explored. In this study, we conducted a detailed analysis of locomotor behavior in wild-type (WT) and KO mice fed a WD or control diet. We investigated changes in the blood metabolome and examined, via PCR, the expression of insulin receptor A and B isoforms and key regulators of their function in the brain. Twelve-month-old KO mice and their WT littermates were fed a WD for three weeks. Nuclear magnetic resonance spectroscopy analysis of plasma samples showed that KO mice on a WD had higher levels of lipids and lipoproteins and lower levels of glucose, lactate, alanine, valine, and isoleucine compared to other groups. SERT-KO mice on the control diet exhibited increased brain levels of both IR A and B isoforms, accompanied by a modest increase in the negative regulator ENPP. The KO mice also displayed anxiety-like behavior and reduced exploratory activity in an open field test. However, when the KO animals were fed a WD, the aberrant expression levels of IR isoforms in the KO mice and locomotor behavior were ameliorated indicating a complex interaction between genetic and dietary factors that might contribute to ADHD-like symptoms. Overall, our findings suggest that the lack of Sert leads to a unique metabolic phenotype in aged mice, characterized by dysregulated IR-related pathways. These changes are exacerbated by WD in the blood metabolome and are associated with behavioral abnormalities.

Executive functioning (EF) is of major interest in the study of cognitive factors involved in obesity. Among EF, shifting is related to behavioral flexibility, and inhibition to the ability to refrain from impulsive behavior. A deficit in those two EF could predict individual difficulties to maintain a healthy lifestyle. Weak evidence of deficits in shifting and inhibition in individuals of higher Body Mass Index (BMI) have been observed. The objective was to clarify the relationship between inhibition and shifting regarding weight status group differences in healthy adults. Two neuropsychological tests from the Test of Attentional Performance (TAP) battery were used to measure EF performance of three groups of men and women: normal-weight (NW, n = 38), overweight (OW, n = 40) and obesity (OB, n = 37). The results show that individuals with higher BMI have lower inhibition capacities and that classically used weight status categories might not capture cognitive variability. No differences in shifting were observed concerning weight status nor BMI. This paper provides new insights on cognitive factors in obesity by presenting data from healthy individuals with overweight and obesity. The results support that assessing inhibition capacities might be of interest in a clinical setting for patients with difficulties to lose weight.

Obesity represents a global health crisis, yet a dichotomy is emerging with classification according to the metabolic state into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). This study aimed to identify distinctive systemic clinical/endocrinological parameters between MHO individuals, employing a comprehensive comparative analysis of 50 biomarkers. Our emphasis was on routine analytes, ensuring cost-effectiveness for widespread use in diagnosing metabolic health.

The study included 182 women diagnosed with obesity referred for bariatric surgery at the Endocrinology, Diabetes, and Metabolism Service of São João Hospital and University Centre in Portugal. MUO was defined by the presence of at least one of the following metabolic disorders: diabetes, hypertension, or dyslipidemia. Patients were stratified based on the diagnosis of these pathologies.

Significantly divergent health-related parameters were observed between MHO and MUO patients. Notable differences included: albumin (40.1 ± 2.2 vs 40,98 ± 2.6 g/L, p value = 0.017), triglycerides (110.7 ± 51.1 vs 137.57 ± 82.6 mg/dL, p value = 0.008), glucose (99.49 ± 13.0 vs 119.17 ± 38.9 mg/dL, p value < 0.001), glycated hemoglobin (5.58 ± 0.4 vs 6.15 ± 1.0%, p value < 0.001), urea (31.40 ± 10.0 vs 34.61 ± 10.2 mg/dL, p value = 0.014), total calcium (4.64 ± 0.15 vs 4.74 ± 0.17 mEq/L, 1 mEq/L = 1 mg/L, p value < 0.001), ferritin (100.04 ± 129.1 vs 128.55 ± 102.1 ng/mL, p value = 0.005), chloride (104.68 ± 1.5 vs 103.04 ± 2.6 mEq/L, p value < 0.001), prolactin (13.57 ± 6.3 vs 12.47 ± 7.1 ng/mL, p value = 0.041), insulin (20.36 ± 24.4 vs 23.87 ± 19.6 μU/mL, p value = 0.021), c peptide (3.78 ± 1.8 vs 4.28 ± 1.7 ng/mL, p value = 0.003), albumin/creatinine ratio (15.41 ± 31.0 vs 48.12 ± 158.7 mg/g creatinine, p value = 0.015), and whole-body mineral density (1.27 ± 0.1 vs 1.23 ± 0.1 g/cm2, p value = 0.016).

Our findings highlight potential additional parameters that should be taken into consideration alongside the commonly used biomarkers for classifying metabolic health in women. These include albumin, urea, total calcium, ferritin, chloride, prolactin, c-peptide, albumin-creatinine ratio, and whole-body mineral density. Moreover, our results also suggest that MHO may represent a transitional phase preceding the development of the MUO phenotype.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Metabolic syndrome (MetS) provides significant risk for coronary disease, however long-term prognosis after percutaneous coronary intervention (PCI) has been understudied. We assessed the prevalence and outcomes of patients with MetS from an Australian PCI cohort. We retrospectively examined data from the Melbourne Interventional Group multicenter PCI registry using a modified definition for MetS including ≥3 of the following: hypertension, diabetes mellitus, dyslipidemia, and body mass index ≥30 kg/m2. Thirty-day outcomes and long-term mortality were compared with patients without MetS. Cox regression methods were used to assess the multivariable effect of MetS on long-term mortality. Of 41,146 patients, 12,228 (34%) had MetS. Patients with MetS experienced greater 30-day myocardial infarction (2.2% vs 1.8%, p = 0.013), whereas patients without MetS had a trend for greater 30-day mortality (3.0% vs 3.4%, p = 0.051) and greater in-hospital major bleeding (1.7% vs 2.4%, p <0.001). After a median follow-up of 5.62 years (Q1 2.03, Q3 8.89), patients with MetS experienced greater mortality (24% vs 19%, p <0.001). After adjustment, MetS was not an independent predictor of long-term mortality (hazard ratio 0.95 confidence interval 0.86 to 1.05, p = 0.35). In sensitivity analyses, MetS-Diabetic patients had the highest, and MetS-NonDiabetic obese patients had the lowest long-term mortality. One in 3 patients who underwent all-comer PCI presented with MetS and experienced greater long-term mortality compared with others. However, this association was lost after adjustment for baseline confounders, highlighting that MetS is a marker of risk after PCI. Our findings support the obesity paradox and confirm robust associations between diabetes mellitus and long-term mortality.

Background: Obesity or overweight raises the risk of developing 13 types of cancer, representing 40% of all cancers diagnosed in the United States annually. Given the ongoing debate surrounding the impact of metabolically healthy obesity (MHO) on cardiovascular outcomes, it is crucial to comprehend the incidence of Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs) and the influence of MHO on these outcomes in cancer patients. Methods: Data of hospitalized cancer patients with and without obesity were analyzed from the National Inpatient Sample 2016-2020. Metabolically healthy patients were identified by excluding diabetes, hypertension, and hyperlipidemia using Elixhauser comorbidity software, v.2022.1. After that, we performed a multivariable regression analysis for in-hospital MACCEs and other individual outcomes. Results: We identified 3,111,824 cancer-related hospitalizations between 2016 and 2020. The MHO cohort had 199,580 patients (6.4%), whereas the MHnO (metabolically healthy non-obese) cohort had 2,912,244 patients (93.6%). The MHO cohort had a higher proportion of females, Blacks, and Hispanics. Outcomes including in-hospital MACCEs (7.9% vs. 9.5%; p < 0.001), all-cause mortality (6.1% vs. 7.5%; p < 0.001), and acute myocardial infarction (AMI) (1.5% vs. 1.6%; p < 0.001) were lower in the MHO cohort compared to the MHnO cohort. Upon adjusting for the baseline characteristics, the MHO group had lower odds of in-hospital MACCEs [adjusted odds ratio (AOR) = 0.93, 95% CI (0.90-0.97), p < 0.001], all-cause mortality [AOR = 0.91, 95% CI (0.87-0.94); p < 0.001], and acute ischemic stroke (AIS) [AOR = 0.76, 95% CI (0.69-0.84); p < 0.001], whereas there were higher odds of acute myocardial infarction (AMI) [AOR = 1.08, 95% CI (1.01-1.16); p < 0.001] and cardiac arrest (CA) [AOR = 1.26, 95% CI (1.01-1.57); p = 0.045] in the MHO cohort compared to the MHnO cohort. Conclusions: Hospitalized cancer patients with MHO exhibited a lower prevalence of in-hospital MACCEs than those with MHnO. Additional prospective studies and randomized clinical trials are imperative to validate these findings, particularly in stratifying MHO across various cancer types and their corresponding risks of in-hospital MACCEs.

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin-melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic.

Menopause is a cardiometabolic transition with many women experiencing weight gain and redistribution of body fat. Hormonal changes may affect also several dimensions of well-being, including sexual function, with a high rate of female sexual dysfunction (FSD), which displays a multifactorial etiology. The most important biological factors range from chronic low-grade inflammation, associated with hypertrophic adipocytes that may translate into endothelial dysfunction and compromised blood flow through the genitourinary system, to insulin resistance and other neuroendocrine mechanisms targeting the sexual response. Psychosocial factors include poor body image, mood disorders, low self-esteem and life satisfaction, as well as partner's health and quality of relationship, and social stigma. Even unhealthy lifestyle, chronic conditions and putative weight-promoting medications may play a role. The aim of the present narrative review is to update and summarize the state of the art on the link between obesity and FSD in postmenopausal women, pointing to the paucity of high-quality studies and the need for further research with validated end points to assess both biomarkers of obesity and FSD. In addition, we provide general information on the diagnosis and treatment of FSD at menopause with a focus on dietary interventions, physical activity, anti-obesity drugs and bariatric surgery.

The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health.

Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

The triglycerides and glucose (TyG) index is a reliable biomarker for estimating insulin resistance; however, evidence regarding the use of the TyG index in individuals with metabolically healthy obesity (MHO) is scarce. Thus, we examined the association between the TyG index and the MHO phenotype.

Apparently healthy men and women aged 18 years or more with obesity (body mass index [BMI] ≥ 30 kg/m2) were allocated into the following groups: MHO and metabolically unhealthy obesity (MUO). The MHO phenotype was defined by obesity and the absence of the following metabolic disorders: elevated triglyceride concentrations, elevated glucose levels, elevated blood pressure, and low HDL-C. The MUO was defined by individuals with obesity and at least one of the aforementioned cardiovascular risk factors.

A total 827 individuals, 605 (73.1%) women and 222 (26.9%) men were enrolled and allocated into the MHO (n = 104) and MUO (n = 723) groups. The adjusted regression analysis by age, sex, BMI, and waist circumference showed that fasting glucose (OR = 0.90; 95% CI: 0.88-0.93), and triglycerides (OR = 0.97; 95% CI: 0.96-0.98), as well as the triglycerides/HDL-C (OR = 0.18; 95% CI: 0.13-0.26), lipid accumulation product (OR = 0.95; 95% CI: 0.93-0.96), visceral adipose index (OR = 0.38; 95% CI: 0.31-0.46), and TyG index (OR = 0.001; 95% CI: 0.000-0.004) are inversely associated with the MHO, while the HDL-C (OR = 1.10; 95% CI: 1.07-1.12) had a direct association.

Our results show that the TyG index is more strongly associated with the MHO phenotype than the lipid and obesity indices.

Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn's disease (CD).

Systematic review and meta-analysis.

PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022.

Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1).

11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, χ2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS.

MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS.

CRD42022346340.

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.

To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE).

The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53).

The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI.