Metabolically Healthy Obese Subjects Research Articles

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

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

A novel criterion of metabolically healthy obesity could effectively identify individuals with low cardiovascular risk among Chinese cohort.

Obesity has become a serious public health problem and brings a heavy burden of cardiovascular disease. Metabolically healthy obesity (MHO) is defined as individuals with obesity with no or only minor metabolic complications. Whether individuals with MHO have a lower cardiovascular risk remains controversial. In this study, a new criterion was used to define MHO and assess its predictive value for cardiovascular events and death. At the same time, the new criterion and the traditional criterion are compared to analyze the differences between different diagnostic criteria. A prospective cohort was established in northeast rural China from 2012 to 2013. Follow-up was conducted in 2015 and 2018 to investigate the incidence of cardiovascular events and survival. Subjects were grouped according to the metabolic health and obesity status. Kaplan-Meier curves were drawn to describe the cumulative risk of endpoint events in the four groups. Cox regression analysis model was constructed to evaluate the risk of endpoint events. Analysis of variance and post hoc analyses were used to calculate and compare differences in metabolic markers between MHO subjects diagnosed by novel and traditional criteria. A total of 9345 participants 35 years of age or older without a history of cardiovascular disease were included in this study. After a median follow-up of 4.66 years, the data showed that participants in the MHO group had no significant increase in the risk of composite cardiovascular events and stroke, but had a 162% increase in the risk of coronary heart disease (HR: 2.62; 95%CI: 1.21-5.67). However, when using conventional criteria for metabolic health, mMHO group had a 52% increase in combined CVD risk (HR: 1.52; 95%CI: 1.14-2.03). By comparing the differences of metabolic indicators between MHO subjects diagnosed by the two criteria, MHO subjects diagnosed by the new criterion had higher WC, WHR, TG, FPG, and lower HDL-C levels except for lower blood pressure, showing more exposure to cardiovascular risk factors. The risk of combined CVD and stroke was not increased in MHO subjects. The new metabolic health criterion is superior to the traditional criterion and can effectively identify individuals with obesity with a lower risk of combined CVD. Blood pressure levels may be responsible for the inconsistent risk of combined CVD in MHO subjects diagnosed with both criteria.

Alternation of the gut microbiota in metabolically healthy obesity: An integrated multiomics analysis.

Although the gut microbiota may be involved in obesity onset and progression, the exact association of the gut microbiota in metabolically healthy obesity (MHO) remains largely unknown. An integrated paired-sample metagenomic analysis was conducted to investigate the gut microbial network and biomarkers of microbial species from the MHO and healthy non-obese subjects in the GMrepo database. Further explorations were performed in the MHO mice model using a multiomics analysis to detect changes in the composition and function of the intestinal microbiome and associated metabolites. In the human study, 314 matched metagenomic data were qualified for the final analysis. We identified seven significantly changed species possibly involved in MHO pathogenesis (MHO-enriched: Bacteroides vulgatus, Megamonas sp; MHO-depleted: Butyrivibrio crossotus, Faecalibacterium prausnitzii, Bacteroides cellulosilyticus; Eubacterium siraeum; Bacteroides massiliensis). In the murine study, we found 79 significantly-changed species which may have possible associations with the MHO phenotype. The depletion of Bacteroides cellulosilyticus was commonly recognized in the human and murine MHO phenotype. Consistent with the metagenomic data, liquid chromatography-mass spectrometry (LC/MS) revealed significantly changed gut metabolites, which may promote MHO pathogenesis by altering the amino acids and lipid metabolic pathways. In the microbe-metabolites interaction analysis, we identified certain fatty acids (Dodecanedioic acid, Arachidic Acid, Mevalonic acid, etc.) that were significantly correlated with the MHO-enriched or depleted species. This study provides insights into identifying specific microbes and metabolites that may involve in the development of obesity without metabolic disorders. Future modalities for MHO intervention may be further validated by targeting these bacteria and metabolites.

Clinical monitored in subjects metabolically healthy and unhealthy before and during a SARS-CoV-2 infection– A cross-sectional study in Mexican population

The COVID-19 disease has forced us to consider the physiologic role of obesity and metabolically healthy and unhealthy status in response to SARS-CoV-2 infection. Hematological, coagulation, biochemical, and immunoinflammatory changes have been informed with a disparity in morbidity and mortality. Therefore, we aimed to investigate the influence of metabolic health on clinical features in a cross-sectional study in Mexican subjects with and without SARS-CoV-2 infection in non-severe stages after a rigorous classification of obese and non-obese subjects who were metabolically healthy and unhealthy. Four groups were formed: 1) metabolically healthy with normal BMI (MHN); 2) metabolically unhealthy with normal BMI (MUN); 3) metabolically healthy obese (MHO); 4) metabolically unhealthy obese (MUO). Serum proinflammatory (TNF-α, MCP-1, IL-1β, and IL-6) and anti-inflammatory (TGF-β, IL-1Ra, IL-4, and IL-10) cytokines, hematological parameters, coagulation, and acute phase components were evaluated. Our results showed that MHO people live with inflammaging. Meanwhile, MUN and MUO subjects develop metaflammation. Both inflammaging and metaflammation cause imperceptible modifications on hematological parameters, mainly in leukocyte populations and platelets, as well as acute phase and coagulation components. The statistical analysis revealed that many clinical features are dependent on metabolic health. In conclusion, MHO subjects seem to be transitioning from metabolically healthy to unhealthy, which is accelerated in acute processes, such as SARS-CoV-2 infection. Meanwhile, metabolically unhealthy subjects independently of BMI have a deteriorating immunometabolic status associated with a hyperinflammatory state leading to multi-organ dysfunction, treatment complications, and severe COVID-19 disease.

Serum proteome profiling reveals differentially expressed proteins between subjects with metabolically healthy obesity and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the leading risk factor for common chronic liver disease and is often regarded as a prevalent metabolic disorder tightly associated with obesity. However, the existence of metabolically healthy obesity (MHO) indicates that some important factors may participate in protecting individuals with MHO free of NAFLD, even with excessive adiposity. To explore factors independent of obesity that may be involved in the occurrence of NAFLD, we performed an iTRAQ-based proteomic study to identify proteins differentially expressed in serum between NAFLD and MHO subjects. Compared with the MHO group, ten proteins were upregulated and five were downregulated significantly in the NAFLD group. Gene Ontology analysis indicated significant changes in the immune response and triglyceride metabolism-related pathways between MHO and NAFLD. We further validated three candidates markedly dysregulated in NAFLD by Western blotting and ELISA, including two upregulated proteins (afamin and apolipoprotein H) and one downregulated protein (apolipoprotein C-1). Detection of serum apolipoprotein H levels in a large-scale cohort with MHO and different stages of NAFLD indicated that apolipoprotein H may be a potential blood biomarker for distinguishing NAFLD from MHO and an independent risk factor for predicting NAFLD.

Prognostic Value of Triglyceride and Glucose Index for Incident Type 2 Diabetes beyond Metabolic Health and Obesity.

BackgroundMetabolically healthy obese (MHO) phenotype is metabolically heterogeneous in terms of type 2 diabetes (T2D). Previously, the triglyceride and glucose (TyG) index has been considered for identifying metabolic health and future risk of T2D. This study aimed to evaluate the risk of incident T2D according to obesity status and metabolic health, categorized by four different criteria and the TyG index.MethodsThe study included 39,418 Koreans without T2D at baseline. The risk of T2D was evaluated based on four different definitions of metabolic health and obesity status and according to the baseline TyG index within each metabolic health and obesity group.ResultsDuring the median follow-up at 38.1 months, 726 individuals developed T2D. Compared with the metabolically healthy non-obese (MHNO) group with low TyG index, the MHO group with high TyG index showed increased risk of T2D in all four definitions of metabolic health with multivariate-adjusted hazard ratios of 2.57 (95% confidence interval [CI], 1.76 to 3.75), 3.72 (95% CI, 2.15 to 6.43), 4.13 (95% CI, 2.67 to 6.38), and 3.05 (95% CI, 2.24 to 4.15), when defined by Adult Treatment Panel III, Wildman, Karelis, and homeostasis model assessment (HOMA) criteria, respectively.ConclusionMHO subjects with high TyG index were at an increased risk of developing T2D compared with MHNO subjects, regardless of the definition of metabolic health. TyG index may serve as an additional factor for predicting the individual risk of incident T2D in MHO subjects.

Myocardial Geometry and Dysfunction in Morbidly Obese Adolescents (BMI 35–40 kg/m2)

This study evaluated the preclinical effect of obesity on the ventricular remodeling in adolescents with morbid obesity, and determined if subjects labelled as metabolically healthy obesity (MHO) presented better heart index than those with metabolically unhealthy obesity (MUO). Prospective case-control research of 45 adolescents (14-year-old) with morbid obesity and 25 normal weight adolescents' gender- and age-matched with Tanner stage 4-5. Left ventricle (LV) was evaluated by conventional Doppler echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Compared to normal-weight subjects, adolescents with morbid obesity presented a high percentage of pathological LV geometry (87%; p<0.01), and systolic and diastolic dysfunctions only detected by E/A ratio (2.0 vs 1.7, p<0.01), global longitudinal strain (-21.0% vs -16.5%, p<0.01), and early diastolic strain rate (3.2 vs 2.2, p<0.01). A correlation was found between impaired cardiac index and body mass index (BMI), high blood pressure, hyperglycemia, low HDL-cholesterol and hypertriglyceridemia. BMI and HDL-cholesterol were the most significant independent variables. No significant differences were found in structural and functional cardiac index when MHO and MUO subjects were compared (global longitudinal strain: -17.0% vs -16.4%, p0.79). Morbidly obese adolescents have an abnormal LV geometry, closely related to BMI, and systolic and diastolic LV dysfunctions. Adolescents labelled as MHO, despite exhibiting better BMI and insulin-resistance values, present the same pathological heart changes as MUO.

Differences in the vascular and metabolic profiles between metabolically healthy and unhealthy obesity

Individuals suffering from severe obesity but not presenting the typical metabolic alterations, are included in a subclass of obesity defined Metabolically Healthy Obesity (MHO). The physiological factors underlying what seems a protective and favourable metabolic profile remain unclear. MHO individuals are more insulin-sensitive, have relatively lower visceral/ectopic fat accumulation and reduced levels of chronic low-grade inflammation, compared to obese subjects with co-morbidities. The study of MHO subjects represents a great opportunity for the recognition of the mechanisms that lead to the vascular and metabolic complications in obesity. Finding the differences among the metabolic profile of visceral adipose tissue between metabolically healthy and unhealthy obesity may lead to future personalized and stratified therapies.This review article summarizes the pathomechanisms and metabolic changes in MHO and metabolically unhealthy obesity (MUO), reviews clinical studies on the subject, and discusses preventive and therapeutic options.

Carotid intima media-thickness is increased in obese children metabolically healthy, metabolically unhealthy, and with metabolic syndrome, compared to the non-obese controls.

The prevalence of obesity continues to increase. Obesity is associated with cardiovascular risk factors: elevated blood pressure, dyslipidemia and glycemic alterations, causing metabolic syndrome. A subgroup of obese, Metabolically Healthy Obese (MHO), appears to be less prone to the development of metabolic disturbances. Carotid intima-media thickness (cIMT) is a non-invasive marker of subclinical atherosclerosis and it is associated with increased risk of CVD events. To investigate the cardiovascular risk, demonstrated through the increase of cIMT in obese subjects without Metabolic Syndrome (MetS), we have studied cIMT in MHO, metabolically unhealthy obese (MUO) and obese with MetS diagnosed with the IDEFICS criteria and compared to a control group. 224 obese children aged 6 to 21 years (13,50 ± 4.01 years) and 103 normal weight subjects aged 7 to 19 years (13.2 ± 4.1 years) were studied. The body mass index (BMI) of the obese children was ≥ the 95th percentile. Based on the IDEFICS criteria, we divided the obese subjects in three groups: MHO if no criteria were out of range, MUO if, at least, one of the criteria was out of range and MetS group if all the IDEFICS criteria were present. In all the subjects cIMT was measured with color Doppler by a vascular surgeon. Differences in the means of the variables were tested by ANOVA. Based on the IDEFICS criteria, 32 subjects were affected by MetS (14..3%), 66 were considered MUO (29.4%) and 126 MHO (56.3%). Comparison of mean cIMT highlighted a significant difference (p < 0.05) between the groups of obese children (MHO, MUO and MetS) and controls for both carotid arteries. We did not find significative difference in the value of cIMT in MHO, MUO and MetS subjects, and all groups showed cIMT value higher compared to cIMT of the controls.

Characterisation of body size phenotypes in a middle-aged Maltese population.

Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist-hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

Healthy Obese Subjects Differ in Chronotype, Sleep Habits, and Adipose Tissue Fatty Acid Composition from Their Non-Healthy Counterparts.

Obesity is not the same in all individuals and two different phenotypes have been described: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The aim of this study was to identify factors that explain metabolic health status in a rigorously matched Spanish population. Subcutaneous and visceral fat, adipocyte size and fatty acid composition, cardiometabolic markers in serum, and lifestyle habits were assessed. Higher physical activity in the mornings (Odds Ratio (95% Confidence Interval) (OR (95% CI) = 1.54 (1.09–2.18), p = 0.01)), earlier bedtimes (8:30–10:30 pm) (OR = 2.11 (1.02–4.36), p = 0.04), a complete breakfast (OR = 1.59 (1.07–2.36), p = 0.02), and a greater number of meals per day (4.10 ± 0.05 vs. 3.93 ± 0.05, p < 0.01), were associated with the MHO phenotype. Concentrations of 20:5 n-3 eicosapentaenoic acid (0.26 ± 0.46 vs. 0.10% ± 0.11%, p = 0.04) and 18:3 n-6 gamma-linolenic acid (0.37 ± 0.24 vs. 0.23% ± 0.22%, p = 0.04) in subcutaneous adipocytes were higher and omental adipocyte size (187 094 ± 224 059 µm3 vs. 490 953 ± 229 049 µm3, p = 0.02) was lower in MHO subjects than in those with MUO. Visceral fat area differed between MHO and MUO subjects (135 ± 60 cm2 vs. 178 ± 85 cm2, p = 0.04, respectively). The study highlights specific lifestyle habits that could form part of obesity therapies, not only involving healthier eating habits but also earlier sleeping and exercise patterns.

Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin.

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

Metabolic Health in Obese Subjects-Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

This study aimed to evaluate the association of genetic variants in lactoferrin (LTF) metabolism-related genes with the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). In total, 161 MHO and 291 MUHO subjects were recruited to the study. The following polymorphisms were genotyped: low-density lipoprotein receptor-related protein (LRP) 2 rs2544390, LRP1 rs4759277, LRP1 rs1799986, LTF rs1126477, LTF rs2239692 and LTF rs1126478. We found significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUHO subjects, with the CT variant associated with lower odds of developing metabolic syndrome than the TT variant. In the total population, significant differences in body weight and waist circumference (WC) were identified between LTF rs1126477 gene variants. A similar association with WC was observed in MUHO subjects, while significant differences in body mass index and low-density lipoprotein cholesterol levels were discovered between LTF rs1126477 gene variants in MHO subjects. Besides, there were significant differences in diastolic blood pressure between LRP1 rs1799986 gene variants in MUHO subjects, as well as in WC and high-density lipoprotein cholesterol levels between LRP1 rs4759277 gene variants in MHO subjects. In conclusion, selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity.

Serum ZAG and Adiponectin Levels Were Closely Related to Obesity and the Metabolically Abnormal Phenotype in Chinese Population.

IntroductionTo explore serum zinc-α2-glycoprotein (ZAG) and adiponectin in metabolically healthy non-obese (MHNO), metabolically healthy obesity (MHO), metabolically abnormal obesity (MAO) and metabolically abnormal diabetic obese (MADO) subjects and the relationship with metabolically phenotypes of obesity.MethodsTwo hundred twenty-five subjects including 32 with MHNO, 40 with MHO, 104 with MAO and 49 with MADO were enrolled. Baseline clinical data and biochemical variables were collected. Serum ZAG and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Metabolically healthy (<3 metabolic abnormalities) or abnormal (≥3 metabolic abnormalities) subjects were classified based on the National Cholesterol Education Program–Adult Treatment Panel III (NCEP/ATP III) criteria. Obesity (body mass index ≥28 kg/m2) was recommended by China Obesity Task Force.ResultsSerum ZAG levels were higher in the MHO group, but were progressively lower in MAO and MADO groups (P all<0.05). In all subjects, total cholesterol, 2-hour postprandial blood glucose and homeostasis model assessment of adiponectin were independent variables to serum ZAG levels. Compared with subjects in the highest tertile of ZAG, the odds ratio (OR) of metabolically abnormal risks of subjects in the lowest and median tertiles of ZAG were higher both in a univariate and three adjustment models (P all<0.05). Serum ZAG could discriminate the metabolically abnormal phenotype with receiver operating characteristic (ROC) curve area of 0.622 (95% CI, 0.539–0.706, P<0.05). Combination of ZAG and adiponectin had improved diagnosis value accuracy, with ROC curve area of 0.703 (95% CI, 0.629–0.776, P<0.05), and 62.7% sensitivity and 73.6% specificity.ConclusionSerum ZAG levels were higher in MHO subjects, but lower in MAO and MADO subjects. The decreased serum ZAG levels were closely related to the metabolically abnormal phenotype of obese patients. Serum ZAG, especially the combination with adiponectin might be the potential diagnostic biomarkers for metabolically abnormal obese patients.

The Impact of BMI Categories on Metabolic Abnormality Development in Chinese Adults Who are Metabolically Healthy: A 7-Year Prospective Study.

PurposeTo determine what metabolic abnormalities develop frequently among metabolically healthy adults over time according to different baseline body mass index (BMI) categories.Patients and MethodsA prospective cohort study was performed on 10,805 adults, who were metabolically healthy at the time of the 2008 survey. Participants were divided into four groups: metabolically healthy obese (MHO), metabolically healthy overweight (MHOW), metabolically healthy normal-weight (MHN), and metabolically healthy underweight (MHU). Modified Poisson regression models were used to evaluate the relationship of BMI with the development of metabolic abnormalities. Association rule mining was used to identify the most frequent abnormalities that developed over time.ResultsCompared with the MHN group, the adjusted relative risks of the MHO group were 1.57 (95% CI: 1.09–2.27) and 2.08 (95% CI: 1.59–2.73) for developing elevated fasting glucose and elevated blood pressure, respectively, after adjusting for lifestyle behaviours and dietary factors. At the end of follow-up, 33 (19.1%) MHO subjects and 342 (16.6%) MHOW subjects had elevated blood pressure as the predominant metabolic syndrome component, whereas 236 (9.0%) MHU subjects had elevated plasma glucose. The results were similar after stratification by sex.ConclusionMHO and MHOW subjects developed elevated blood pressure most frequently, and MHU subjects developed elevated blood glucose most commonly, regardless of sex.

Cardiovascular Risk Factors Associated With the Metabolically Healthy Obese (MHO) Phenotype Compared to the Metabolically Unhealthy Obese (MUO) Phenotype in Children.

Background: In pediatric age the prevalence of obesity is high. Obese children who do not have other risk factors than excess weight have been defined as “metabolically healthy obese” (MHO).Aim: The aim of this study is to evaluate, in a population of obese children, the prevalence of the MHO and “metabolically unhealthy obese” (MUO) phenotype. Furthermore, we evaluated the distribution of Uric Acid, HOMA index and Waist-Height ratio (W-Hr) in the MHO and MUO sub-groups and the impact of these non-traditional risk factors on the probability to be MUO.Methods: In 1201 obese children and adolescents [54% males, age (±SD) 11.9 (±3.0) years] weight, height, waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, pubertal status, glucose, insulin, HDL cholesterol, triglycerides and Uric Acid serum values were assessed. MUO phenotype was defined as the presence of at least one of the following risk factors: SBP or DBP ≥ 90th percentile, glycaemia ≥ 100 mg/dl, HDL cholesterol <40 mg/dl, triglycerides ≥100 mg/dl (children <10 years) or ≥130 mg/dl (children ≥10 years). A multivariate logistic regression analysis was used to estimate the association between MUO phenotype and non-traditional cardiovascular risk factors.Results: The prevalence of the MUO status was high (61%). MUO subjects were more often male, older and pubertal (p < 0.001). The levels of the three non-traditional risk factors were significantly higher in MUO children compared to MHO children (p < 0.001) and all of them were independent predictors of the fact of being MUO [OR 1.41 (95% CI 1.24–1.69); 1.15 (95% CI 1.06–1.23) and 1.03 (95% CI1.01–1.05) for Uric Acid, HOMA index and W-Hr, respectively]. About 15% of MHO subjects had serum Uric Acid, HOMA index and W-Hr values within the highest quartile of the study population.Conclusion: The prevalence of MUO subjects in a large pediatric population is high and serum Uric Acid, HOMA index and W-Hr values are independent predictors of the probability of being MUO. A non-negligible percentage of subjects MHO has high values of all three non-traditional risk factors.

Metabolically healthy obesity (MHO) in the Malmö diet cancer study – Epidemiology and prospective risks

Background/aimsMetabolically healthy obesity (MHO) remains controversial, since the underlying mechanisms behind this phenotype remain unclear. We aimed to investigate the characteristics of MHO, as well as prospective risks. MethodA cross-sectional analysis was carried out in a subsample of 3812 obese subjects selected from the Malmo diet cancer study (n=28,403). Subjects with MHO (n=1182) were defined by having no records of hospitalization for somatic disorders prior to baseline examination. MHO subjects were further compared to subjects with metabolically unhealthy obesity, MUO (obese individuals with at least one recorded hospitalization: n=2630), and all non-obese cohort controls (NOC; n=24,591). Moreover, prospective risk analyses for incident cardiovascular (CV) morbidity and mortality were carried out. ResultsCompared to MUO individuals, MHO individuals reported a significantly lower proportion of sedentary life style (p=0.009), but also significantly lower HbA1c (p=0.012), fasting glucose (p=0.001) and triglyceride levels (p=0.011) than MUO. Cox-regression analysis (follow-up 20±6 years) showed both a significantly lower all-cause mortality risk for MHO individuals as compared to MUO (p=0.001), as well as lower incident CV morbidity risk (p=0.001). When comparing MHO individuals to NOC, there were no significant differences in neither mortality risk nor incident CV morbidity risk. ConclusionCompared to MUO individuals, MHO individuals presented with a higher level of physical activity, a more favorable lipid- and glucose profile and a lower prospective risk of total mortality and CV morbidity during 20-years follow-up. Notably, no significant differences could be seen in mortality and CV morbidity risks when comparing MHO subjects to non-obese controls.

P5293Effect of metabolically health obesity on carotid intima-media thickness in general population: a community-based cohort study

Abstract Introduction Obesity is a common and independent risk factor for all-cause mortality. More specifically, obesity is a major component of atherosclerosis in association with metabolic disorders including metabolic syndrome (MetS), resulting in various cardiovascular diseases (CVD). Alternatively, obese subjects without MetS are prevalent, also referred to as metabolically healthy obesity (MHO). However, most preceding studies regarding MHO have been limited by small cohorts. Therefore, the effect of MHO on atherosclerosis in the general population remains unclear. Purpose In this study, we sought to clarify the effect of MHO on carotid intima-media thickness (IMT) as a marker of early stage atherosclerosis using a community-based cohort in general population. Methods We examined subjects who underwent medical check-up at our University Hospital. We defined obesity as body mass index ≥25.0 kg/m2. Abdominal obesity, defined as waist circumstance at umbilical level ≥85 cm in men and ≥90 cm in women, was obligatory for the diagnosis of MetS. In addition to abdominal obesity, any two of the following three abnormalities should be observed for the diagnosis of MetS, [1] Dyslipidemia: triglyceride ≥150 mg/dL, HDL-C &lt;40 mg/dL, or use of lipid lowering medication, [2] Hypertension: systolic blood pressure ≥130 mmHg, diastolic blood pressure ≥85 mmHg, or use of antihypertensive medication, and [3] Hyperglycemia: fasting plasma glucose ≥110 mg/dL or use of hypoglycemic medication. MHO was defined as obese subjects without MetS, whereas we defined metabolically unhealthy obesity (MUO) as obese subjects with MetS. We defined carotid plaque as IMT ≥1.1 mm. Results Among 1,241 subjects, 857 subjects (69%) were categorized in the normal body weight group, whereas 275 subjects (22%) were categorized as MHO, and 109 subjects (9%) were categorized as MUO. Compared to non-obese subjects, prevalence of classical cardiovascular risk factors including hypertension, diabetes mellitus, and dyslipidemia increased in subjects with MHO, and further increased in those with MUO. IMT was higher in obese subjects compared to those without obesity. Similarly, the prevalence of carotid plaque formation was also higher in obese subjects. Multivariable logistic regression analysis demonstrated that age ≥60 years, male sex, hypertension, diabetes mellitus, MHO subjects (Odds ratio [OR]; 1.6, p=0.005), and MUO subjects (OR 1.7, p=0.04) were independently associated with carotid plaque formation. There was no statistical difference in the risk of carotid plaque formation between subjects with MHO and MUO. IMT and Carotid Plaque Conclusions IMT and the prevalence of carotid plaque are higher in both subjects with MHO and MUO compared to non-obese subjects in the general population. We need to take obesity regardless of the presence of MetS into consideration as high-risk subjects for subsequent CVD.

Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis.

Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk. The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis. A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72). Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.

Obesity and Risk of Peptic Ulcer Disease: A Large-Scale Health Check-Up Cohort Study.

The association between obesity and peptic ulcer disease (PUD) is inconclusive. To evaluate the association of obesity and metabolically healthy obesity (MHO) with PUD risk, we performed a retrospective cohort study of 32,472 subjects without PUD at baseline who underwent repeated health examinations. Participants were stratified by body mass index (BMI) and metabolically healthy state. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard modelling. During the follow-up period, 1940 PUD cases occurred. PUD, particularly gastric ulcer (GU), had significantly higher cumulative incidence in obese subjects compared to non-obese subjects (p value < 0.001). The HR for developing GU was 1.32 (95% CI, 1.16–1.49; p value <0.001); after adjusting for confounding factors (lifestyle, metabolic, and Helicobacter pylori status), the association was no more significant (p value = 0.789). For duodenal ulcer (DU), cumulative incidence between obese and non-obese groups was not significantly different (p value = 0.464). The risk of developing DU in the obese group was not significantly different from the non-obese group (HR 0.95; 95% CI, 0.83–1.09; p value = 0.469) and consistently showed no association after adjusting for metabolic parameters (p value = 0.199). Furthermore, MHO subjects had no increase in GU or DU risks. In this large cohort study, PUD risk was not associated with obesity or MHO.