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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. [ABSTRACT FROM AUTHOR]

Abstract Background and aims The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. Methods This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. Results This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. Conclusion According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.

Background and aims: The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. Methods: This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. Results: This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. Conclusion: According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women. [ABSTRACT FROM AUTHOR]

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. • Metabolically healthy status was found in 31.1% of normal weight subjects and in 20.0% of overweight/obesity subjects. • In a 17.4-year follow-up, the risk of MARCE was not increased in the metabolically healthy overweight/obese subjects. • In contrast, unhealthy metabolic status was a significant predictor of MARCE irrespective of baseline BMI. • Compared to healthy metabolic status, the metabolically unhealthy overweight/obese group had a 133% increase in risk. [ABSTRACT FROM AUTHOR]

As We Were and as We Should Be, Combined Exercise Training in Adults with Schizophrenia: CORTEX-SP Study Part I. Med. Sci. Sports Exerc., Vol. 56, No. 1, pp. 73-81, 2024. Introduction: Given the health benefits and the role of exercise as an anti-inflammatory adjuvant program, this study aimed to determine the effectiveness of a combined exercise program on cardiorespiratory fitness (CRF), body composition, and biochemical levels in adults with schizophrenia (SZ) characterized at baseline as metabolically unhealthy overweight with low CRF. Methods: Participants diagnosed with SZ (n = 112, 41.3 ± 10.4 yr, 28.7% women) were randomly assigned into a treatmentas-usual control group (n = 53) or a supervised exercise group (n = 59, 3 d·wk-1 ). Each combined exercise session consisted of both a low-volume high-intensity interval training (<10 min of high-intensity time per session) and a resistance circuit-training program. All variables were assessed before and after the intervention (20 wk). For the assessment of CRF, a peak cardiopulmonary exercise test on a cycle ergometer was used. Results: After the intervention, participants from the exercise group (n = 51) showed increases in CRF (P < 0.001) through peak oxygen uptake (L·min-1 ; Δ = 17.6%; mL·kg-1 ·min-1, Δ = 19.6%) and the metabolic equivalent of task (Δ = 19%), with no significant changes (P > 0.05) in body composition and biochemical variables. However, the treatment-as-usual group (n = 38) did not show any significant change in the study variables (P > 0.05). Between-group significant differences (P ≤ 0.05) were observed in CRF, first ventilatory threshold, and heart rate peak after the intervention period, favoring the exercise group. Conclusions: This study demonstrated that a supervised combined exercise program in people with SZ helps to maintain body composition values and improve CRF levels. This could lead to an important clinical change in the characterization from metabolically unhealthy overweight to a metabolically healthy overweight population. Hence, exercise should be considered a co-adjuvant program in the treatment of the SZ population [ABSTRACT FROM AUTHOR]

BackgroundBody mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health.ResultsThe discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q

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 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.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Summary: Diagnosis of metabolically healthy obesity (MHO) and its definition do not have universal criteria in the pediatric age group. Hence, this scoping review aims to identify the components, the cutoff points, and the definition of MHO in children and adolescents. A comprehensive, systematic search was conducted in PubMed, Scopus, EMBASE, and Google Scholar databases. A consensus‐based definition of MHO was developed through a Delphi process involving an international panel of 23 experts. This review included a total of 63 non‐randomized studies, published between 2007 and 2022. According to our consensus (≥80% agreement), the proposed definition for MHO included the following components: high‐density lipoprotein cholesterol >40 mg/dl (or >1.03 mmol/l), triglycerides ≤150 mg/dl (or ≤1.7 mmol/l), fasting plasma glucose <100 mg/dl (or <5.6 mmol/l), a measure of insulin, and systolic and diastolic blood pressure ≤90th percentile. Therefore, MHO was defined as the absence of the above metabolic risk factors; and those children and adolescents with one or more criteria were considered as metabolically unhealthy. A universal definition of MHO will allow comparisons between studies in the field of childhood obesity and can be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). Methods: The study included 136 obese subjects scheduled for bariatric surgery and 52 normal‐weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow‐ups were performed at the baseline and 6 months after bariatric surgery. Results: Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p <.05). Parafovea SCP, average DCP, parafovea DCP, and perifovea DCP vessel densities significantly improved in patients with obesity 6 months after surgery, compared to baseline (54.21% vs. 52.97%, 54.43% vs. 50.95%, 58.29% vs. 55.54% and 55.76% vs. 51.82%, respectively, all p <.05). Multivariable analyses showed that baseline blood pressure and insulin were independent predictors of vessel density changes 6 months after surgery. Conclusions: Retinal microvascular impairment occurred mainly in MetS rather than MHO patients. Retinal microvascular phenotype improved 6 months after bariatric surgery and baseline blood pressure and insulin status may be key determinants. OCTA may be a reliable method to evaluate the microvascular complications associated with obesity. [ABSTRACT FROM AUTHOR]

Background: Evidence about the associations between obesity severity, metabolic status and risk of incident cardiovascular disease (CVD) in adults with obesity remains limited. Methods: The study included 109,301 adults with obesity free of prior CVD based on the UK Biobank cohort. Metabolic status was categorized into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes) and metabolically unhealthy obesity (MUO). Obesity severity was classified into three levels: class I (body mass index of 30.0–34.9 kg/m2), II (35.0–39.9) and III (≥40.0). Cox proportional hazards models were used for analyses. Results: There were 8059 incident CVD events during a median follow‐up of 8.1 years. MUO was significantly associated with a 74% increased CVD risk compared with MHO (HR = 1.74, 95% CI: 1.62–1.83). There was a significant interaction between obesity severity and metabolic status on an additive scale regarding CVD risk. When taking class I obesity as reference, class II was nonsignificantly associated with an increased risk of CVD in the MHO group (HR = 1.07, 95% CI: 0.90–1.27), while class III was significantly related to increased risks of CVD (HR = 1.48, 95% CI: 1.12–1.96). In the MUO group, both classes II and III were significantly related to increased risks of CVD. Significant subgroup effects of age (p =.009) and sex (p =.047) were observed among participants with MUO but not in the MHO group. Conclusions: Both elevated obesity severity and MUO were significantly associated with increased risks of CVD in adults with obesity, while metabolic status could modify the relationship between obesity severity and CVD risk. More research is needed to further clarify the relationship. [ABSTRACT FROM AUTHOR]

Background: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term. Methods: We examined 970 individuals of 18 to 45 years of age. The participants’ mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy (p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight (p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants (p = 0.073). Conclusion: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Abstract Background Investigating the effect of metabolic disorders on chronic kidney disease (CKD) in the presence or the absence of obesity is of great importance. This study aimed to examine the independent and joint relationships of obesity and metabolic syndrome (MetS) with CKD. Methods The present study was performed on 9,762 participants from the baseline phase of the Ravansar non- communicable diseases (RaNCD) study. Thereafter, the CKD was estimated by glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. All the included participants were categorized into the following four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy overweight/obesity (MHO), and metabolically unhealthy overweight/obesity (MUO). Finally, Logistic regression analysis was used to estimate the odds ratio (ORs). Results The mean age of the included participants was 47.33 ± 8.27 years old, %48.16 (4,701) of whom were men. As well, 1,058(10.84%) participants had CKD (eGFR less than 60 ml/min/1.73m2). The overweight/obesity was not significantly associated with odds of CKD. The odds of CKD in male subjects with MetS was 1.48 times higher than non-MetS ones (95% CI: 1.10, 2.01). After adjusting the confounders, the odds of CKD were 1.54 times (95% CI: 1.12, 2.11) higher in the MUNO and 2.22 times (95% CI: 1.44, 3.41) higher in the MUO compared to MHNO phenotype in male subjects. The odds of CKD in the MUNO and MUO was 1.31 times (95% CI: 1.10, 1.60) and 1.23 times (95% CI: 1.01, 1.54) higher than MHNO phenotype in female subjects, respectively. Conclusion The odds of CKD were higher in MUNO and MUO phenotypes. Therefore, lifestyle modification is recommended to control normal weight and healthy metabolism.

Rising obesity rates and the increasing prevalence of stroke in the metabolically healthy obese and overweight (MHOO) necessitate examining its association in younger (18-44 year) populations and analyzing acute ischemic stroke (AIS) trends and outcomes in MHOO vs. metabolically healthy non-obese or overweight (MHnOO). Data from the United States National Inpatient Sample (2016-2019) was analyzed to identify young MHOO and MHnOO AIS patients using ICD-10-CM codes. Metabolically healthy status was defined by excluding hospitalization records with diagnostic codes for hypertension, diabetes, and dyslipidemia. Demographics, trends, and outcomes were compared using appropriate statistical approaches. Of 26,949,310 young metabolically healthy hospitalizations between 2016 and 2019, 47,795 had AIS, of which 4,985 were MHOO and 42,810 were MHnOO. The median age of AIS hospitalization was 35 years, and primarily female and white. From 2016 to 2019, AIS incidence rose slightly, which was significant only for the MHnOO cohort. The in-hospital mortality rate was significantly lower in the MHOO cohort (6.0 % vs. 8.6 %, p < 0.001). Hospitalization length and cost did not differ substantially between groups. Adjusted multivariable analysis revealed no significant difference in AIS hospitalization risk between MHOO and MHnOO (aOR: 1.02, p=0.701), with subgroup analysis in males (aOR: 0.88, p=0.161) or females (aOR: 1.06, p=0.363). However, all-cause in-hospital mortality (ACIHM) in AIS had lower odds in the MHOO vs. MHnOO cohorts (aOR: 0.60, p=0.021). Our study finds a rising trend of AIS hospitalizations in young metabolically healthy adults, with obesity or overweight status not being associated with AIS hospitalization. We identify an "obesity paradox" of lower odds for ACIHM for AIS hospitalizations in the MHOO cohort. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundPhytochemicals have been recently studied as adjuvants for the treatment of obesity. No study has investigated the association of phytochemical-rich foods with metabolically unhealthy overweight/obesity phenotype (MUOW/O). This study aimed to determine the association of dietary phytochemical index (DPI) with MUOW/O based on Karelis criteria among Iranian female adults.MethodsIn this cross-sectional study, a total of 228 overweight and obese women aged 18–48 years were included. Anthropometric measurements were evaluated for all participants. A validated 147-item Food Frequency Questionnaire (FFQ) was used for dietary assessment. DPI was calculated as [dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)] × 100. Participants’ body composition and biochemical parameters of Karelis criteria [triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, and high-sensitivity C-reactive protein (hs-CRP)] were determined.ResultsThe mean age of the study participants was 36.69 ± 9.20, and the mean DPI score was 26.23 ± 9.48 among participants with MUOW/O phenotype. After controlling for potential confounders, women in the highest tertile of DPI had lower odds for MUOW/O phenotype [odds ratio (OR): 0.23, 95% confidence interval (CI): 0.07–0.68, P = 0.008] compared to the lowest tertile. Among the components of Karelis criteria, homeostatic model assessment for insulin resistance (HOMA-IR) was significantly associated with MUOW/O phenotype in the fully adjusted model (OR: 0.29, 95% CI: 0.10–0.79, P = 0.01).ConclusionWe found a significant association between DPI and MUOW/O phenotype in Iranian women. Prospective studies are needed to confirm these findings.

Background: Investigating the effect of metabolic disorders on chronic kidney disease (CKD) in the presence or the absence of obesity is of great importance. This study aimed to examine the independent and joint relationships of obesity and metabolic syndrome (MetS) with CKD.  METHODS : The present study was performed on 9,762 participants from the baseline phase of the Ravansar non- communicable diseases (RaNCD) study. Thereafter, the CKD was estimated by glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. All the included participants were categorized into the following four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy overweight/obesity (MHO), and metabolically unhealthy overweight/obesity (MUO). Finally, Logistic regression analysis was used to estimate the odds ratio (ORs).Results: The mean age of the included participants was 47.33 ± 8.27 years old, %48.16 (4,701) of whom were men. As well, 1,058(10.84%) participants had CKD (eGFR less than 60 ml/min/1.73m2). The overweight/obesity was not significantly associated with odds of CKD. The odds of CKD in male subjects with MetS was 1.48 times higher than non-MetS ones (95% CI: 1.10, 2.01). After adjusting the confounders, the odds of CKD were 1.54 times (95% CI: 1.12, 2.11) higher in the MUNO and 2.22 times (95% CI: 1.44, 3.41) higher in the MUO compared to MHNO phenotype in male subjects. The odds of CKD in the MUNO and MUO was 1.31 times (95% CI: 1.10, 1.60) and 1.23 times (95% CI: 1.01, 1.54) higher than MHNO phenotype in female subjects, respectively.Conclusion: The odds of CKD were higher in MUNO and MUO phenotypes. Therefore, lifestyle modification is recommended to control normal weight and healthy metabolism. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction Asians develop type 2 diabetes at a lower body mass index (BMI) compared with other races, which is partly because of Asian‐specific fat depots. Sex plays a role in fat deposition, regardless of race. This retrospective cohort study aimed to investigate the association among fatty liver, sex and type 2 diabetes in non‐obese Japanese. Materials and Methods The participants in this study (13,596 men and 6,037 women) were aged 30–64 years, and had undergone health checkups between 2013 and 2015, in Aichi, Japan. Baseline BMI was categorized as follows:

Obesity and its’ associated metabolic diseases such as type 2 diabetes and cardiometabolic disorders are significant health problems confronting many countries. A major driver for developing obesity and metabolic dysfunction is the uncontrolled expansion of white adipose tissue (WAT). Specifically, the pathophysiological expansion of visceral WAT is often associated with metabolic dysfunction due to changes in adipokine secretion profiles, reduced vascularization, increased fibrosis, and enrichment of proinflammatory immune cells. A critical determinate of body fat distribution and WAT health is the sex steroid estrogen. The bioavailability of estrogen appears to favor metabolically healthy subcutaneous fat over visceral fat growth while protecting against changes in metabolic dysfunction. Our review will focus on the role of estrogen on body fat partitioning, WAT homeostasis, adipogenesis, adipocyte progenitor cell (APC) function, and thermogenesis to control WAT health and systemic metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Body composition is closely related to metabolic health status. Visceral adipose tissue (VAT) dysfunction contributes to metabolic syndrome. However, results regarding subcutaneous adipose tissue (SAT) and skeletal muscle are controversial. We aimed to determine the association of indices of body composition with abnormal metabolic phenotype in China. Methods: A total of 3, 954 subjects (age 50.2 ± 11.7 years) with body mass index (BMI) more than 18.5 kg/m2 from Pinggu Metabolic Disease Study were analyzed. Quantitative computed tomography (QCT) was performed to measure total adipose tissue (TAT), VAT, SAT area, and lumbar skeletal muscle area (SMA). Participants were divided into six groups on the basis of BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Chinese Diabetes Society criteria. Results: 63.4%, 39.5%, and 23.3% participants were classified as metabolically healthy phenotype in individuals with normal weight, overweight and obese, respectively. Individuals in the highest TAT, VAT, and VAT/TAT ratio category had higher risk of being metabolically unhealthy than individuals in the lowest group (all p <0.01). While, risk for metabolically unhealthy was reduced significantly in the highest SMA/TAT ratio category when compared with the lowest category in individuals with normal wight and overweight (both p <0.05). Risk for metabolically unhealthy was reduced significantly in the highest SAT category when compared with the lowest category (OR=0.555, 95%CI: 0.360-0.856, p =0.008) in individuals with obese after adjustment for age, sex and BMI. However, skeletal muscle index (SMI) showed no significant association with the metabolically healthy status in different BMI categories (p >0.05). The VAT and VAT/TAT ratio were better diagnostic values of indicators to differentiate metabolically unhealthy subjects from controls compared with other indicators, such as TAT, SAT, SMI, SMA/TAT ratio. Conclusions: Higher visceral adipose tissue was closely associated with metabolically unhealthy phenotype in Chinese adults. Subcutaneous adipose tissue might be a protective factor for metabolic health status only in obese individuals. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity is increasing worldwide. Obesity is associated with severe health effects. Abdominal obesity has a strong association with metabolic dysfunction. A subgroup of people with central obesity has been identified without typical metabolic disorders associated with obesity that has been known metabolically healthy abdominal obese (MHAO). The purpose of this review is to evaluate the MHAO phenotype in the context of type 2 DM incidence, risk of cardiovascular diseases, and all-cause of mortality. Methods: This is a protocol of systematic review. We will search PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, and ProQuest. Additional studies will be identified through manual searching of reference lists. Quantitative studies evaluating abdominal obesity phenotype outcomes in adults will be included. Primary results will be assaying abdominal obesity phenotype results, including DM2 incidence, cardiovascular disease risk, and all-cause mortality. Two reviewers will independently screen full-text articles and abstract data. Statistical Analysis Used: Potential conflicts will be resolved through discussion. Results: The study methodological quality (or bias) will be appraised using appropriate tools. If feasible, we will conduct a random-effects meta-analysis. The researchers will also assess the quality of the articles independently based on Newcastle-Ottawa scale. Conclusions: The results of this review will provide a useful reference for the effect of abdominal obesity on metabolic dysfunction and cardiovascular or all-cause mortality [ABSTRACT FROM AUTHOR]

Materials and Methods: Functional vascular age in 2000 patients was assessed using cardiac risk profiler (vascular profiler-genesis), over a period of 3 years and 3 months between October 2016 and January 2020. The cardiovascular interpretations generated were used for the measurement of central arterial stiffness. The metabolically healthy groups were compared with the metabolically nonhealthy groups for the relevance of the triple co-association of HbA1c, arterial stiffness, and hypertension in screening the patients in regular standard care. The mean age of the patients was 53 years. Mann–Whitney test was used for the statistical analysis. Results: The mean age was 53.3 ± 12 years. HbA1c was 7% in 530 and 1470 patients, respectively. The lipid profile in comorbid scenario (n = 2000 [M = 1170 and F = 830]) revealed mean LDL-C mg/dL values of< 100, 100–150, >150 in 1380, 520, and 100 patients, respectively. A total of 1000 patients had the duration of diabetes 10 years, respectively. Arterial stiffness markers-Ankle Brachial Index and Carotid-Femoral Pulse Wave Velocity (CFPWV) were assessed and cluster analyses was performed using the metabolically healthy (HbA1c 7 and aortic augmentation index @ HR75 > 14 and with known hypertension (n = 230). The difference in the triple co-association of HbA1c (glycemic status), hypertensive status, and arterial stiffness was statistically significant when compared between the metabolically healthy (n = 50) vs. the metabolically nonhealthy cohort all across (n = 230) (P = 0.0457)Conclusion: The clustered metabolic marker approach is a tool to identify and stratify patients with diabetes based on the metabolic risk to prevent complications and possibly improve outcomes.

Obesity and its’ associated metabolic diseases such as type 2 diabetes and cardiometabolic disorders are significant health problems confronting many countries. A major driver for developing obesity and metabolic dysfunction is the uncontrolled expansion of white adipose tissue (WAT). Specifically, the pathophysiological expansion of visceral WAT is often associated with metabolic dysfunction due to changes in adipokine secretion profiles, reduced vascularization, increased fibrosis, and enrichment of pro-inflammatory immune cells. A critical determinate of body fat distribution and WAT health is the sex steroid estrogen. The bioavailability of estrogen appears to favor metabolically healthy subcutaneous fat over visceral fat growth while protecting against changes in metabolic dysfunction. Our review will focus on the role of estrogen on body fat partitioning, WAT homeostasis, adipogenesis, adipocyte progenitor cell (APC) function, and thermogenesis to control WAT health and systemic metabolism.

IntroductionBody composition is closely related to metabolic health status. Visceral adipose tissue (VAT) dysfunction contributes to metabolic syndrome. However, results regarding subcutaneous adipose tissue (SAT) and skeletal muscle are controversial. We aimed to determine the association of indices of body composition with abnormal metabolic phenotype in China.MethodsA total of 3, 954 subjects (age 50.2 ± 11.7 years) with body mass index (BMI) more than 18.5 kg/m2 from Pinggu Metabolic Disease Study were analyzed. Quantitative computed tomography (QCT) was performed to measure total adipose tissue (TAT), VAT, SAT area, and lumbar skeletal muscle area (SMA). Participants were divided into six groups on the basis of BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Chinese Diabetes Society criteria.Results63.4%, 39.5%, and 23.3% participants were classified as metabolically healthy phenotype in individuals with normal weight, overweight and obese, respectively. Individuals in the highest TAT, VAT, and VAT/TAT ratio category had higher risk of being metabolically unhealthy than individuals in the lowest group (all p0.05). The VAT and VAT/TAT ratio were better diagnostic values of indicators to differentiate metabolically unhealthy subjects from controls compared with other indicators, such as TAT, SAT, SMI, SMA/TAT ratio.ConclusionsHigher visceral adipose tissue was closely associated with metabolically unhealthy phenotype in Chinese adults. Subcutaneous adipose tissue might be a protective factor for metabolic health status only in obese individuals.

• The study resurveyed subjects every 4–5 years to capture dynamic changes. • The long-term stability of MHO may be an exception, not the norm. • The 4.4-year predicted probability of transition from the MHO to MUO phenotype was 0.19. • One-third of the MHO subjects were unhealthy after 12–15 years. • Metabolic deterioration of the metabolite BMI phenotype conferred an increased risk of CVD. The prognostic significance of obesity phenotypes is under debate, and few studies have characterized their transition trajectories. This study examined the natural courses of different phenotypes and their associations with cardiovascular disease risks. A total of 1827 participants were followed for 14 years and re-evaluated every 4–5 years. Four metabolite BMI phenotypes were determined according to overweight or obesity (BMI ≥ 24 kg/m2) and metabolic health status (≤1 Adult Treatment Panel III criteria, excluding waist circumference). Cardiovascular risks were assessed by evaluating baPWV and hypertension, diabetes and chronic kidney disease (CKD) development. More than 20% of participants changed their initial phenotypes within 5 years. One-third of healthy overweight/obese (MHO) individuals became unhealthy, and only 10.6% regressed to a healthy normal weight (MHN) at the end of follow-up. Compared with MHN participants, MHO participants had higher odds of increased baPWV (OR: 1.18, 95% CI, 0.42–3.33) and increased risks of incident hypertension (HR: 1.87, 95% CI, 1.18–2.98) and diabetes (HR: 2.61, 95% CI, 1.35–5.03). Metabolic deterioration during follow-up resulted in an increased risk of baPWV and clinical diseases. The natural trajectory of metabolite BMI phenotypes is time-varying, and interventions for both healthy and unhealthy overweight/obese individuals should be widely recommended. [ABSTRACT FROM AUTHOR]

Background and Aim: Obesity and metabolic conditions may be related to non‐alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community‐based population. Methods: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. Results: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64–3.65), 2.75 (95% CI: 1.91–3.94), and 7.41 (95% CI: 4.94–11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65–5.53; T3 vs T1: 9.17, 95% CI: 5.33–15.79). Conclusion: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level. [ABSTRACT FROM AUTHOR]

Objective: We performed the cohort study to evaluate the association between BMI, high-sensitivity C-reactive protein (hs-CRP) and the conversion from metabolically healthy to unhealthy phenotype in Chinese adults.Design: Metabolically healthy was defined as participants without history of metabolic diseases and with normal fasting blood glucose level, glycated Hb A1c level, blood pressure, lipid profile, serum uric acid level and liver ultrasonographic findings at baseline. Participants were either classified into normal weight (18·5 ≤ BMI < 24·0 kg/m2) and overweight (BMI ≥ 24·0 kg/m2) based on baseline BMI, or low (<1 mg/l) and high (≥1 mg/l) groups based on baseline hs-CRP. The conversion from metabolically healthy to unhealthy phenotype was deemed if any of the metabolic abnormalities had been confirmed twice or more during 5 years of follow-up.Results: Included were 4855 (1942 men and 2913 women, aged 36·0 ± 8·9 years) metabolically healthy Chinese adults. We identified 1692 participants who converted to metabolically unhealthy phenotype during the follow-up. Compared with their counterparts, the adjusted hazards ratio of the conversion was 1·19 (95 % CI 1·07, 1·33) for participants with overweight, while it was 1·15 (95 % CI 1·03, 1·29) for those with high hs-CRP level (≥1 mg/l). Further adjustment of hs-CRP did not materially change the association between BMI and the conversion. However, the association between hs-CRP and the conversion was not significant after further adjustment of BMI. The sensitivity analysis generated similar results to main analysis.Conclusion: BMI was associated with the risk of the conversion from metabolically healthy to unhealthy status in Chinese adults. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Asians develop type 2 diabetes at a lower body mass index (BMI) compared with other races, which is partly because of Asian‐specific fat depots. Sex plays a role in fat deposition, regardless of race. This retrospective cohort study aimed to investigate the association among fatty liver, sex and type 2 diabetes in non‐obese Japanese. Materials and Methods: The participants in this study (13,596 men and 6,037 women) were aged 30–64 years, and had undergone health checkups between 2013 and 2015, in Aichi, Japan. Baseline BMI was categorized as follows: <18.5, 18.5–19.9, 20–22.9, 23–24.9, 25–27.4 and ≥27.5 kg/m2. Fatty liver was diagnosed by abdominal ultrasonography. The joint effect of BMI and fatty liver on the incidence of type 2 diabetes was assessed, stratified by sex. Results: During follow up, 738 men and 138 women developed type 2 diabetes. Compared with the BMI of 20–22.9 kg/m2 without fatty liver group, the BMI of 20–22.9 kg/m2 with fatty liver was associated with a higher risk of type 2 diabetes in men, but not in women. Furthermore, men with a BMI of 23–24.9 and 25–27.4 kg/m2 without fatty liver had no significant type 2 diabetes risk, whereas women with a BMI of 23–24.9 and 25–27.4 kg/m2, regardless of fatty liver, had an increased risk. Conclusions: These results suggest the association between fatty liver and type 2 diabetes in non‐obese Asians is different by sex; fatty liver increases diabetes risk among male, not female, non‐obese Asians. [ABSTRACT FROM AUTHOR]

Karamatollah Rahmanian,1 Mohammad Shojaei,2 Abdolreza Sotoodeh Jahromi21Research Center for Social Determinants of Health, Community Medicine Department, Faculty of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran; 2Research Center for Non-communicable Diseases, Internal Diseases Department, Faculty of Medicine, Jahrom University of Medical Sciences, Jahrom, IranPurpose: The incidence of obesity is globally increasing and it is a predisposing factor for morbidity and mortality. This study assessed the prevalence of metabolically unhealthy (MU) individuals and its determinants according to body mass index (BMI).Materials and method: In our cross-sectional study, 891 persons aged 30 years or older participated. Participants were classified as obese (BMI ≥30 kg/m2), overweight (BMI 25–

Over 650 million adults are obese (body mass index ≥ 30 kg/m2) worldwide. Obesity is commonly associated with several comorbidities, including cardiovascular disease and type II diabetes. However, compiled estimates suggest that from 5 to 40% of obese individuals do not experience metabolic or cardiovascular complications. The existence of the metabolically unhealthy obese (MUO) and the metabolically healthy obese (MHO) phenotypes suggests that underlying differences exist in both tissues and overall systemic function. Macrophage accumulation in white adipose tissue (AT) in obesity is typically associated with insulin resistance. However, as plastic cells, macrophages respond to stimuli in their microenvironments, altering their polarization between pro- and anti-inflammatory phenotypes, depending on the state of their surroundings. The dichotomous nature of MHO and MUO clinical phenotypes suggests that differences in white AT function dictate local inflammatory responses by driving changes in macrophage subtypes. As obesity requires extensive AT expansion, we posit that remodeling capacity with adipose expansion potentiates favorable macrophage profiles in MHO as compared with MUO individuals. In this review, we discuss how differences in adipogenesis, AT extracellular matrix deposition and breakdown, and AT angiogenesis perpetuate altered AT macrophage profiles in MUO compared with MHO. We discuss how non-autonomous effects of remote organ systems, including the liver, gastrointestinal tract, and cardiovascular system, interact with white adipose favorably in MHO. Preferential AT macrophage profiles in MHO stem from sustained AT function and improved overall fitness and systemic health.

Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite outcome of death, nonfatal reinfarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups. At baseline, 54.6% of patients were included in the MHNW group, 26.4% in the MUNW, 5.9% in the MHO and 13.1% in the MUO, with no sex-differences in the distribution of phenotypes. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men than in women (RR: 1.19 vs. 0.6). The Kaplan–Meier curves for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (log rank test, p = 0.006), this effect being more prominent in men (log 11.20; p = 0.011), than in women (log 7.98; p = 0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% 1.11–1.54 in MUO group), whereas in women the risk was confined to metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23–9.98, MUNW group). Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS.

Background: The prevalence of obesity is increasing worldwide. Obesity is associated with severe health effects. Abdominal obesity has a strong association with metabolic dysfunction. A subgroup of people with central obesity has been identified without typical metabolic disorders associated with obesity that has been known metabolically healthy abdominal obese (MHAO). The purpose of this review is to evaluate the MHAO phenotype in the context of type 2 DM incidence, risk of cardiovascular diseases, and all-cause of mortality. Methods: This is a protocol of systematic review. We will search PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, and ProQuest. Additional studies will be identified through manual searching of reference lists. Quantitative studies evaluating abdominal obesity phenotype outcomes in adults will be included. Primary results will be assaying abdominal obesity phenotype results, including DM2 incidence, cardiovascular disease risk, and all-cause mortality. Two reviewers will independently screen full-text articles and abstract data. Statistical Analysis Used: Potential conflicts will be resolved through discussion. Results: The study methodological quality (or bias) will be appraised using appropriate tools. If feasible, we will conduct a random-effects meta-analysis. The researchers will also assess the quality of the articles independently based on Newcastle-Ottawa scale. Conclusions: The results of this review will provide a useful reference for the effect of abdominal obesity on metabolic dysfunction and cardiovascular or all-cause mortality

Background: Limited therapeutic tools and an overwhelming clinical demand are the major limiting factors in pediatric obesity management. The optimal protocol, environment, body mass index (BMI) change targets and duration of obesity-oriented interventions remain to be elucidated. Aims: We aimed to characterize the singularities of follow-up, anthropometric and metabolic evolution of a large cohort of pediatric patients with obesity in a specialized university hospital outpatient obesity unit. Patients and methods: Follow-up duration (up to seven years), attrition rate and anthropometric and metabolic evolution of 1300 children and adolescents with obesity were studied. An individualized analysis was conducted in patients attaining a high level of weight loss (over 1.5 BMI-SDS (standard deviation score) and/or 10% of initial weight; n = 252; 19.4%) as well as in “metabolically healthy” patients (n = 505; 38.8%). Results: Attrition rate was high during the early stages (11.2% prior to and 32.5% right after their initial metabolic evaluation). Mean follow-up time was 1.59 ± 1.60 years (7% of patients fulfilled 7 years). The highest BMI reduction occurred in the first year (−1.11 ± 0.89 SDS, p < 0.001 in 72.5% of patients). At the end of the follow-up, improvements in glucose and lipid metabolism parameters were observed (both p < 0.05), that were highest in patients with the greatest weight reduction (all p < 0.01), independent of the time spent to achieve weight loss. The pubertal growth spurt negatively correlated with obesity severity (r = −0.38; p < 0.01) but patients attaining adult height exceeded their predicted adult height (n = 308, +1.6 ± 5.4 cm; p < 0.001). “Metabolically healthy” patients, but with insulin resistance, had higher blood pressure, glucose, uric acid and triglyceride levels than those without insulin resistance (all p < 0.05). Preservation of the “metabolically healthy” status was associated with BMI improvement. Conclusions: Behavioral management of children with obesity can be effective and does not impair growth but is highly conditioned by high attrition. The best results regarding BMI reduction and metabolic improvement are achieved in the first year of intervention and can be preserved if follow-up is retained.

Background: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term., Methods: We examined 970 individuals of 18 to 45 years of age. The participants' mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy ( p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight ( p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants ( p = 0.073)., Conclusion: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Highlights • 10.05% of Chinese adults was metabolically healthy obese. • Metabolically healthy obese increased the risk of cardiovascular disease. • This association was similar both in age group, sex, and resident area. Abstract Background Epidemiologic evidence on metabolically healthy obese (MHO) phenotype and cardiovascular diseases (CVD) risk remains controversial. Aims We aim to examine the relationship between MHO and risk of CVD among the Chinese population. Methods The China Health and Retirement Longitudinal Study is a prospective cohort study of 7849 participants aged ≥45 years without CVD at baseline. Metabolic health status was assessed based on blood pressure, triglycerides, high-density lipoprotein cholesterol, glycated hemoglobin, fasting glucose, and C-reactive protein. A cutoff point of body mass index of 24.0 kg/m2 was used to define over-weight/obesity (≥24.0 kg/m2) or normal weight (<24.0 kg/m2). CVD was based on self-reported doctor's diagnosis of heart problems and stroke. Incidence rate ratio (IRR) with 95% confidence interval (CI) was deduced from modified Poisson regression. Results During a mean 3.6 years of follow-up, 880 incident CVD events were recorded. 789 (10.05%) were identified MHO among 3321 (42.3%) obese individuals. Compared with metabolically healthy normal weight individuals, the multivariable adjusted IRR of CVD was 1.33 (95%CI: 1.19–1.49) for MHO, 1.29 (95%CI: 1.22–1.38) for metabolically unhealthy normal weight, and 1.61 (95%CI: 1.51–1.75) for metabolically unhealthy obese in the full adjusted model. Conclusions MHO individuals are associated with the increased risk of cardiovascular diseases among the Chinese population. [ABSTRACT FROM AUTHOR]

Abstract Background Small scale cohorts demonstrated an association between body mass index (BMI) and diastolic function in a metabolically healthy population. We aimed to characterize the relation between BMI and diastolic function in a relatively large cohort of metabolically healthy obese with preserved ejection fraction. Methods and results Echocardiograms of metabolically healthy patients between 2011 and 2016, who had no significant valvulopathies or atrial fibrillation, and had preserved ejection fraction, were retrospectively identified and analyzed. Metabolically healthy was defined as lack of known diabetes mellitus, hypertension, and hyperlipidemia. Patients were categorized into 4 groups according to BMI - normal BMI 18.5‐25, overweight 25.01‐30, obese 30.01‐35, morbidly obese >35 kg/m2. The cohort consisted of 7057 individuals, 54.9% males, with a mean age 54 years. Patients in higher BMI groups more commonly demonstrated abnormalities in most echocardiographic parameters associated with diastolic dysfunction, including left atrial volume index>34 ml/m2, E/e′>14, e' lateral<10 cm/s, e' septal<7 cm/s, tricuspid regurgitation velocity>2.8 m/s and systolic pulmonary artery pressure≥36 mmHg (p <0.01 for all comparisons). Morbidly obese carried the highest risk compared to those with normal BMI. There were no significant differences between the groups in rates of readmission due to heart failure. Conclusion High BMI is associated with increased risk of diastolic dysfunction even in metabolically healthy patients. Additional trials are needed in order to evaluate whether these echocardiographic findings translate into clinical implications. Highlights • The cohort included 7057 metabolically healthy individuals with preserved ejection fraction • Patients with higher BMI had higher rates of parameters associated with diastolic dysfunction • Morbidly obese carried the highest risk compared to those with normal BMI [ABSTRACT FROM AUTHOR]

Although the associations of vitamin D with obesity and metabolic abnormalities have been reported, the role of vitamin D in the transition of obesity phenotype remains unclear but is highly desired since it is crucial to identify potential methods for obesity management. Therefore, we aimed to investigate the relationship between vitamin D and the risk for metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO) in metabolically healthy children with 2 years of follow-up. Data were collected from a population-based cohort consisting of 6424 metabolically healthy children aged 6–16 years at baseline. Metabolic abnormalities including hypertension, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), hyperglycemia, and hyperuricemia were assessed both at baseline and follow-up. Baseline serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured as exposure. The obesity phenotype transition was evaluated by weight status with the combination of metabolic health status from baseline to follow-up. During a 2-year follow-up, 889 (13.8 %) incident MUO cases occurred. For participants with obesity, each 10 nmol/L increment in 25(OH)D concentrations was associated with a 21 % (95% CI : 13 %∼43 %) and a 7 % (95%CI: 1 %∼14 %) decreased risk in high TG and hyperuricemia, respectively. A 51 % (95%CI: 22 %∼69 %) lower risk of MUO was observed in participants with sufficient vitamin D levels (≥50 nmol/L) compared to those with vitamin D deficiency (<30 nmol/L). Besides, among children who were MHO at baseline, those with sufficient vitamin D levels (≥50 nmol/L) were more likely to transition to metabolically healthy normal weight (MHNW) than vitamin D deficient individuals (<30 nmol/L). Vitamin D may prevent the development of MUO and help increase the transition from MHO to MHNW. The findings highlight that vitamin D might be an effective nutrient for obesity management. • Children with sufficient vitamin D levels have a significant reduction in the risk of metabolically unhealthy obesity. • Metabolically healthy obese children with adequate vitamin D are more likely to become healthy normal weight. • Vitamin D has been speculated to be an effective nutrient for obesity management in children. [ABSTRACT FROM AUTHOR]

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically healthy (MH) prepubertal and pubertal children and their associations with pro-inflammatory and endothelial damage biomarkers, taking puberty into account. A total of 1444 Spanish children aged 3–17 years (48.9% males, 66% prepubertal, 47.1% with obesity) were recruited. Blood pressure, anthropometric and biochemical parameters were measured, and children were categorized as having a MU or MH status according to risk factors. Retinol, carotenes, tocopherols, total antioxidant capacity (TAC), oxidized low-density lipoprotein and selected pro-inflammatory and endothelial damage biomarkers were analyzed. General linear models adjusted for age, sex, recruitment center and body mass index, partial correlations and stepwise linear regressions were performed. Lower carotenes and tocopherols levels were found in MU than in MH children. Plasma TAC was lower in prepubertal and higher in pubertal children with obesity compared to normal-weight children. Antioxidants and oxidative stress biomarkers showed novel associations with several pro-inflammatory and endothelial damage biomarkers, with pubertal differences, supporting the importance of considering both the antioxidant and oxidative stress status and puberty in the prevention of metabolic diseases in childhood.

Aims The objective of this study was to determine the prevalence and the associated factors of metabolically unhealthy in normal-weight and metabolically healthy in obese. Methods We analyzed the data of a representative sample of 986 participants recruited among adult population of north of Iran. Data were collected regarding demographic characteristics, lifestyle, body mass index, abdominal obesity measures, blood pressure, and lipid profiles. The participants were classified as metabolically healthy obese (MHO) and metabolically unhealthy normal-weight (MUNW). Metabolically unhealthy was defined as the presence of  ≥2 non-obese components of metabolic syndrome based on ATP III criteria. Results The prevalence rate of MUNW and MHO accounted for 17.2% and 15.1% respectively. Mean age of participants with metabolically unhealthy was significantly greater than metabolically healthy in both normal weight and overweight/obese (P = 0.001). The results of multiple logistic regression analysis showed in normal-weight individuals, a significant association of MUNW was found with age group of 50–59 years(OR = 3.83, 95%CI: 1.71-8.57) and 60–70 years by OR = 4.74(95%CI:1.79-12.54) as compared with age group of 20–29 years. It was also associated with current smoking. While metabolically healthy state in overweight/obese was inversely associated with age 50–59 years by OR = 0.26 (95%CI:0.13-0.54) and age 60–70 years by OR = 0.15 (95%CI:0.05- 0.39) and higher WC by OR = 0.47 (95%CI:0.31-0.72) but positively associated with female-sex by OR = 1.74 (95%CI:1.07-2.82). Conclusion Aging and smoking are significantly associated with metabolic abnormalities in normal-weight while aging, abdominal obesity negatively and female positively associated with metabolically healthy in obese. [ABSTRACT FROM AUTHOR]

Metabolically healthy obesity (MHO), a phenotype of obesity considered to be of lower cardiovascular risk, is still a controversial concept. This study aimed to investigate the presence of subclinical systemic microvascular dysfunction in individuals with MHO. This was a cross-sectional study in which 112 volunteers were allocated into three groups: metabolically healthy normal weight (MHNW), MHO, or metabolically unhealthy obesity (MUO). Obesity was defined as a body mass index (BMI) ≥ 30 kg/m2. MHO was defined as the absence of any component of metabolic syndrome, except waist circumference. Microvascular reactivity was evaluated using cutaneous laser speckle contrast imaging. Mean age was 33.2 ± 7.66 years. The median BMI in the MHNW, MHO and MUO groups was 23.6, 32.8, and 35.8 kg/m2, respectively. Baseline microvascular conductance values were lower in the MUO group (0.25 ± 0.08 APU/mmHg) than in MHO (0.30 ± 0.10 APU/mmHg) and MHNW groups (0.33 ± 0.12 APU/mmHg) (P = 0.0008). There were no significant differences regarding endothelial-dependent (acetylcholine stimulation or postocclusive reactive hyperemia) or endothelial-independent (sodium nitroprusside stimulation) microvascular reactivity among the groups. Individuals with MUO had lower baseline systemic microvascular flow than those with MHNW or MHO, but endothelium-dependent or endothelium-independent microvascular reactivity were not changed in any of the groups. The relatively young age of the study population, the low frequency of class III obesity, or the strict definition of MHO (absence of any metabolic syndrome criteria) might account for the lack of difference of microvascular reactivity among MHNW, MHO or MUO. • Individuals with metabolically unhealthy obesity have lower systemic microvascular flow than those with healthy obesity. • Endothelium-dependent or -independent microvascular reactivity were not different in any of the groups. • The relatively young age of the study population and the low frequency of class III obesity may explain the results. [ABSTRACT FROM AUTHOR]

Few studies have described the characteristics of metabolically healthy individuals with excess fat in the Chinese population. This study aimed to prospectively investigate the natural course of metabolically healthy overweight/obese (MH-OW/OB) adults, and to assess the impact of weight change on developing metabolic abnormalities. During 2009-2010, 525 subjects without any metabolic abnormalities or other obesity-related diseases were evaluated and reevaluated after 5 years. The subjects were categorized into two groups of overweight/obese and normal weight based on the criteria of BMI by 24.0 at baseline. At follow-up, the MH-OW/OB subjects had a significantly increased risk of developing metabolically abnormalities compared with metabolically healthy normal-weight (MH-NW) individuals (risk ratio: 1.35, 95% confidence interval: 1.17-1.49, p value < 0.001). In the groups of weight gain and weight maintenance, the MH-OW/OB subjects was associated with a larger increase in fasting glucose, triglycerides, systolic blood pressure, diastolic blood pressure and decrease in high-density lipoprotein cholesterol comparing with MH-NW subjects. In the weight loss group, no significant difference of changes of metabolic parameters was observed between MH-OW/OB and MH-NW adults. This study verifies that MH-OW/OB are different from MH-NW subjects. Weight management is needed for all individuals since weight change has a significant effect on metabolic health without considering the impact of weight change according to weight status. [ABSTRACT FROM AUTHOR]

Background: A subset of obese individuals does not exhibit metabolically unfavorable features; this group is referred to as metabolically healthy obese (MHO). Serum concentrations of polychlorinated biphenyls (PCBs), which are chemicals with endocrine-disrupting properties, have been shown to be lower in MHO than in metabolically unhealthy obese (MUO). Objective: We studied PCB serum concentrations during and after weight loss and their relation with metabolic health. Design: We determined metabolic health features (weight, blood pressure, lipids, inflammation, and glucose metabolism) and serum PCB concentrations of 27 PCBs in a cohort of 184 overweight and obese subjects. Metabolic health was evaluated with the use of the criteria of the metabolic syndrome (MetS) [metabolic syndrome according to Adult Treatment Panel III criteria present (MetS+) or metabolic syndrome according to Adult Treatment Panel III criteria absent (MetS?)] or with extended criteria with inflammation and insulin resistance taken into account (MUO compared with MHO). Participants were treated with lifestyle counseling or bariatric surgery. A metabolic and toxicological re-evaluation was performed after 6 and 12 mo. Results: At baseline, serum ΣPCB concentrations were significantly higher in MUO than in MHO (ΣPCBs: 138 ±105 compared with 365 ± 481 ng/g lipid weight; P = 0.01) but not in MetS+ compared with MetS? subjects. No difference was detected in the percentage increase in PCB serum concentrations in MetS+ compared with MetS? subjects (median: 58% compared with 43% and 31% compared with 69% at 6 and 12 mo, respectively). The comparison of persistent with resolved MetS and MUO did not reveal any difference in ΣPCB concentration increments (median: 49% compared with 58% at 12 mo for MUO; P > 0.05). In a regression model with age, smoking, and body mass index corrected for, PCB serum concentrations at baseline were not predictive of the persistence or resolution of a metabolically unfavorable state. Conclusion: Our study indicates that the increment in serum concentrations of PCBs does not differ according to metabolic health and does not seem to influence the beneficial metabolic health effects of weight loss. [ABSTRACT FROM AUTHOR]

Background A subgroup of obese patients without metabolic disorders has been identified and defined as metabolically healthy but morbidly obese (MHMO). Objectives To compare Roux-en-Y gastric bypass (RYGB) outcomes between MHMO and metabolically unhealthy morbidly obese (MUMO) patients to assess whether the obesity phenotype could affect the results. Setting A university-affiliated tertiary care center. Methods One hundred nineteen consecutive patients underwent RYGB; 102 completed the 2-year follow-up and were divided into 2 groups (MHMO and MUMO) according to Wildman criteria, including blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood sugar, C-reactive protein (CRP), and homeostasis model assessment of insulin resistance (HOMA-IR). Weight loss and metabolic parameter changes were analyzed. Results Twenty-one of 102 (20.6%) patients were identified as MHMO; they were mostly women (90.5%) and were significantly younger than MUMO patients (39.4±9.1 yr versus 47.2±10, P = .001); 12.6% were lost to follow-up. MHMO phenotype was significantly associated with a greater percentage of excess body mass index loss ( P = .03), independent of gender, age, and redo procedures. All metabolic parameters were significantly improved 2 years after surgery in the MUMO group. HOMA-IR, CRP, and triglycerides were significantly lower 2 years after surgery in the MHMO group, whereas fasting blood sugar and HDL-C were unchanged. At 2 years of follow-up, 92.3% of the population was metabolically healthy. Conclusions RYGB is an effective procedure to achieve weight loss and had a strong positive metabolic effect in both MHMO and MUMO phenotypes. RYGB led to an increase of the metabolically healthy status and may prevent or delay the onset of metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: To explore the metabolically healthy (MH) to metabolically unhealthy (MU) transition and its association with body size change patterns according to age.Methods: In total, 12,910 MH subjects were evaluated in 2013 and reevaluated in 2020. A MH state was defined as a score ≤ 1, and a MU state was defined as a score > 1 on the National Cholesterol Education Program-Adult Treatment Panel III criteria.Results: Approximately 27.0% of MH individuals converted to MU status over the follow-up. Compared with young adults, middle adulthood individuals had a 1.33-fold (95% CI: 1.21-1.46) and late adulthood individuals had a 1.55-fold (95% CI: 1.41-1.70) risk of transition. The body mass index (BMI)/waist circumference (WC)-value change was positively associated with metabolic deterioration; the association weakened with age. With stable normal body size (defined by BMI) as a reference, changing phenotype categories of maximum overweight [hazard ratio (HR): 1.75; 95% CI: 1.56-1.95], non-obesity to general obesity (HR: 2.96; 95% CI: 2.47-3.54) and stable general obesity (HR: 2.44; 95% CI: 1.92-3.10) conferred a higher risk of metabolic deterioration.Conclusions: MH status is a transient state, especially in late and middle adulthood. Individuals transitioning to an obese phenotype should receive attention for concomitant metabolic deterioration. [ABSTRACT FROM AUTHOR]

Background: The relationship between osteocalcin and atherosclerosis remains unclear. This might be due to different degrees of confounding from factors that are associated with serum osteocalcin level, such as metabolic-related variables. This study aimed to investigate the relationship between serum osteocalcin level and carotid intima-media thickness (C-IMT) in a metabolically healthy population. Methods: A total of 476 subjects with normal values for weight, glucose tolerance, blood pressure, and lipids (age range, 20-75 years; 155 men, 201 premenopausal women, 120 postmenopausal women) from the Shanghai Obesity Study were recruited for this cross-sectional study. Subjects with a history of cardiovascular disease or carotid plaque were excluded. C-IMT was measured by ultrasonography. Serum osteocalcin level was assessed by an electrochemiluminescence immunoassay. Results: Median C-IMT in the entire study population was 0.55 mm with an interquartile range of 0.50-0.60 mm. C-IMT in premenopausal women was significantly lower than that in men and postmenopausal women (all P< 0.001). The median (interquartile range) of serum osteocalcin level in the entire population was 17.02 (13.31-21.47) ng/mL. Serum osteocalcin level in postmenopausal women was significantly higher than that in men and premenopausal women (all P < 0.001), while the level of serum osteocalcin in men was also significantly higher than that in premenopausal women (P< 0.001). No significant correlation was found between C-IMT and serum osteocalcin level in either men or postmenopausal women. There was a significant, inverse correlations between C-IMT and serum osteocalcin level in premenopausal women after adjustment of age, but this association was eliminated after adjustment for other confounding factors. Conclusions: Serum osteocalcin level was not independently associated with C-IMT in a metabolically healthy Chinese population. [ABSTRACT FROM AUTHOR]