Definitions Of Metabolically Healthy Obesity Research Articles

Metabolically healthy obesity: from epidemiologyand mechanisms to clinical implications.

The concept of metabolic health, particularly in obesity, has attracted a lot of attention in the scientific community, and is being increasingly used to determine the risk of cardiovascular diseases and diabetes mellitus-related complications. This Review assesses the current understanding of metabolically healthy obesity (MHO). First, we present the historical evolution of the concept. Second, we discuss the evidence for and against its existence, the usage of different definitions of MHO over the years and the efforts made to provide novel definitions of MHO. Third, we highlight epidemiological data with regard to cardiovascular risk in MHO, which is estimated to be moderately elevated using widely used definitions of MHO when compared with individuals with metabolically healthy normal weight, but potentially not elevated using a novel definition of MHO. Fourth, we discuss novel findings about the physiological mechanisms involved in MHO and how such knowledge helps to identify and characterize both people with MHO and those with metabolically unhealthy normal weight. Finally, we address how the concept of MHO can be used for risk stratification and treatment in clinical practice.

From Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Populations: Decreased Bone Turnover Bioactivity.

A bone turnover marker reflects bone bioactivity. The effects of metabolically healthy compared with metabolically unhealthy obesity phenotypes on bone metabolism are not well understood. The aim of the study was to evaluate differences of bone transformation indexes in these two obesity phenotypes. A total of 419 obese subjects were recruited, 64 with metabolically healthy obesity (MHO) and 351 with metabolically unhealthy obesity (MuHO). BTMs and clinical parameters were measured. Bone metabolism indexes, including tartrate resistant acid phosphatase (TRACP, p < 0.05), β carboxyl terminal peptide of collagen (β-CTX, p < 0.01), and bone alkaline phosphatase (BAP, p < 0.01), were higher in subjects with MHO than MuHO, but parathyroid hormone (PTH) was lower (p < 0.05). The between-group difference in serum calcium was not significant. Low bone turnover activity was associated with significant hyperglycemia, insulin resistance, and body fat index (p < 0.05). Multivariate logistic regression found that TRACP, β-CTX, and BAP were independently associated with the presence of MHO. Receiver operating characteristic curve analysis found that the maximum area under the curve value for the definition of MHO was (0.8221) and was obtained when sex, age, body mass index (BMI), TRACP, β-CTX and BAP were included simultaneously, resulting in a sensitivity of 81.25% and specificity: 72.3%. The MHO group had significantly increased circulating TRACP and β-CTX compared with the MuHO group and BAP levels were within the physiological range. Obesity with the metabolically healthy phenotype had slightly increased bone turnover activity that may be an early compensatory response of skeletal metabolism to the increased BMI.

Alteration of Branched-Chain and Aromatic Amino Acid Profile as a Novel Approach in Studying Polycystic Ovary Syndrome Pathogenesis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive-age women and predisposes them to the development of metabolic disturbances. Recent research has shown that several metabolic factors may play a role in PCOS pathogenesis, and it has been suggested that an alteration in the amino acid profile might be a predictive sign of metabolic disorders. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are concepts that have attracted scientific attention; however, a universal definition has not been established yet for these terms. Already existing definitions of MHO involve the coexistence of obesity with the absence or minimal presence of other metabolic syndrome parameters. A group of 326 women, 209 diagnosed with PCOS and 117 healthy individuals, participated in this study. Multiple parameters were assessed, including anthropometrical, biochemical, and hormonal ones, and gas-liquid chromatography, combined with tandem mass spectrometry, was used to investigate the amino acid profile. Statistical analysis revealed noticeably higher levels of all aromatic amino acids in PCOS women compared to the control group: phenylalanine 47.37 ± 7.0 vs. 45.4 ± 6.09 nmol/mL (p = 0.01), tyrosine 61.69 ± 9.56 vs. 58.08 ± 8.89 nmol/mL (p < 0.01), and tryptophan 53.66 ± 11.42 vs. 49.81 ± 11.18 nmol/mL (p < 0.01); however, there was no significant difference in the "tryptophan ratio" between the PCOS and control group (p = 0.88). A comparison of MHO and MUO PCOS women revealed that LAP, leucine, and isoleucine concentrations were significantly higher among the MUO subgroup: respectively, 101.98 ± 34.74 vs. 55.80 ± 24.33 (p < 0.001); 153.26 ± 22.26 vs. 137.25 ± 25.76 nmol/mL (p = 0.04); and 92.92 ± 16.09 vs. 82.60 ± 18.70 nmol/mL (p = 0.02). No significant differences in BMI, fasting glucose, and HOMA-IR between MHO and MUO were found: respectively, 35.0 ± 4.8 vs. 36.1 ± 4.6 kg/m2 (p = 0.59); 88.0 ± 6.0 vs. 87.73 ± 6.28 mg/dL (p = 0.67); and 3.36 ± 1.70 vs. 4.17 ± 1.77 (p = 0.1). The identification of altered amino acid profiles in PCOS holds potential clinical implications. Amino acids may serve as biomarkers for diagnosing and monitoring the metabolic status of individuals with PCOS. The alteration of BCAAs and AAAs may be involved in PCOS pathogenesis, but the underlying mechanism should be further investigated.

Risk factors, cutoff points, and definition of metabolically healthy/unhealthy obesity in children and adolescents: A scoping review of the literature.

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.

Metabolically healthy and unhealthy obesity: contemporary views on the main differences. Review

The review is devoted to discussion of the actual medical and social problem of obesity which is an independent risk factor for many chronic noninfectious diseases including cardiovascular pathology. However, since not all people with obesity demonstrate metabolic complications and obesity itself doesn’t negatively influence on the course of diseases or pathological states or threaten with a premature death from them, the review emphasize on the existing of two obesity phenotypes: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). Some contemporary views on the main differences between existing obesity phenotypes are expounded in the review. The definition of MHO, contemporary criteria of its revelation and its prevalence in population are elucidated in detail in the review as well as some risk factors of transformation of MHO to MUO with a consideration of the latter signs are also discussed. The data about existing risks of adverse clinical outcomes in MHO compared with MUO are presented. The contemporary views on the main differences between MHO and MUO based on such characteristics as insulin action, diet, physical activity, duration and quality of sleep, adipose tissue biology (distribution of fat accumulations, adipogenesis and lipogenesis, adipocyte size, oxygenation of adipose tissue, extracellular matrix remodeling and interstitial fibrosis, immune adipose tissue cells and inflammation, lipolytic activity of adipose tissue and adiponectin production) are interpreted in the review. MHO is emphasized to be a new conception for stratification of the patients at high risk of cardiovascular and metabolic diseases. Taking into account that different criteria of healthy metabolism are used today for evaluation of MHO, the future investigations should propose not only united definition of MHO but select some contingents of persons with MHO whose are at high risk of cardiovascular and metabolic diseases.

Zerk eragiten du obesitatea duen pertsona bat metabolikoki osasuntsua izatea edo ez izatea?

Obesitatea osasun-arazo garrantzitsua bihurtu da xxi. mendean, mundu osoan milioika pertsonei eragiten diena. Obesitatearekin batera hainbat komorbilitate agertzen direla onartuta dago, eta horiek bizi-itxaropena murriztearekin lotzen dira. Hala ere, obesitatea pairatzen duten pertsona guztiengan ez da egoera hori antzeman; izan ere, ikusi izan da hainbatek obesitatearekin lotutako asaldura kardiometabolikoen aurrean babesa erakusten dutela. Obesitatea pairatzen duten baina komorbilitaterik ez duten horiek metabolikoki osasuntsuak diren obesoak (MOO) dira. Gaur egun, MOO kontzeptuaren definizioa aldatu egiten da iturri bibliografikoen arabera; hortaz, ez da oso zehatza. Gainera, MOO identifikatzeko irizpide unibertsalik ez dagoenez, prebalentzia-datuak nabarmen aldatzen dira ikerketen artean. MOO eta metabolikoki osasuntsuak ez diren obesoen (MOEO) artean hainbat ezberdintasun fisiologiko, funtzional eta patologiko identifikatu dira: MOOek, adibidez, intsulinarekiko sentikortasunari eusten diote, eta ez dute ez hipertentsiorik ez dislipemiarik pairatzen. Gainera, MOOak 2 motako diabetesaren, gaixotasun kardiobaskularren eta beste heriotza-kausen aurrean babestuta daudela ikusi izan da. Ezberdintasun horien erantzuleetako batzuk MOOen eta MOEOen artean ezberdina den erraietako gantzaren metaketa eta gantz-ehunaren disfuntzioa direla proposatu da. Ondorioz, gorputz-masaren indizea komorbilitateen eraginez agertuko diren konplikazioen larritasunarekin zuzenki erlazionatuta egon arren, gantz-metaketaren kokalekuak eta gantz-ehunaren disfuntzioak erlazio zuzenagoa dute obesitatearekin batera etorri ohi diren komorbilitateen garapenarekin.

Association between the phenotype of metabolically healthy obesity and the risk of myocardial infarction

Abstract Aim This study aimed to investigate the associations between the metabolically healthy obesity (MHO) and the risk of myocardial infarction (MI) in a Russian population sample. Materials and methods A random population sample of men and women aged 45–69 years old at baseline was examined in 2003–2005 in a Russian city; after that the cohort was followed-up for 12 years on the average (2003–2016). A sub-cohort of subjects with body mass index (BMI) ≥30 kg/m2 at baseline was selected for present study (3157 individuals, 73.2% women); of those, 3008 subjects free from baseline history of MI/acute CHD was included for analysis. The data on incident myocardial infarction (MI) were ascertained from register of MI, two repeated examinations and repeated postal interviews during 12-year follow-up of the cohort. We used two definitions of MHO: by NCEP ATPIII, 2001 (the presence of 2 or less components of the metabolic syndrome) and by IDF 2005 (waist circumference (WC) ≥94 cm in men and ≥80 cm in women regardless of risk factors). Multivariable Cox regression was conducted using the SPSS package (V. 13.0). Results The prevalence of MHO at baseline ranged from 20% (by IDF) to 45% (by NCEPATPIII) in obese sub-cohort. Among subjects with MHO at baseline, about one half of subjects developed metabolically unhealthy obesity phenotype (MUO) during 12-years. Women were more likely to retain MHO (32%) and more frequent transited from MUO to MHO (14%) compared to men (22% and 6% by IDF criteria, correspondently) during 12 years. The relative risk of incident MI in subjects with MUO at baseline was 1.9 times higher than in those with MHO (HR 1.9, 95% CI 1.2–2.9) by NCEPATP III. Among men, the relative risk of MI in those with MUO (by NCEP ATP III) was 2 times higher than in a group with MHO (HR 2.1, 95% CI 1.1–4.0). Among women, the relative risk of MI in those with MUO (by NCEP ATP III) was 2.2 (95% CI 1.2- 4.2) compared to MHO group. Using the IDF criteria, the relative risk of MI in MUO vs. MHO was 2.2 (95% CI 0.9–5.7) in men and 2.2 (95% CI: 0.9–5.7) in women. Conclusions In this study population, men aged 45–69 have more frequent progression from metabolically healthy to metabolically unhealthy obesity during 12 years compared to women. The 12-year risk of incident MI in subjects with MUO was approximately twice higher compared to MHO and the excess risk was similar in men and women. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Wellcom Trust

Impact of Metabolically Healthy Obesity in Patients with Andrological Problems

BackgroundAlthough the pathogenic role of metabolically complicated obesity (MCO) in erectile dysfunction (ED), major adverse cardiovascular events (MACE), and male infertility has been widely studied, that of metabolically healthy obesity (MHO) has been poorly investigated. AimTo assess the role of MHO in the pathogenesis of ED, prediction of MACE, and male reproductive health. MethodsA consecutive series of 4,945 men (mean age, 50.5 ± 13.5 years) with sexual dysfunction (SD) (cohort 1) and 231 male partners of infertile couples (mean age, 37.9 ± 9.1 years; cohort 2) were studied. A subset of men with SD (n = 1,687) was longitudinally investigated to evaluate MACE. All patients underwent clinical, biochemical, erectile function, and flaccid penile color Doppler ultrasound (PCDU) assessment. Infertile men also underwent scrotal and transrectal ultrasound; semen analysis, including interleukin (IL-) 8; and prostatitis-like symptom assessment. MHO was defined as body mass index >30 kg/m2 with high-density lipoprotein cholesterol level >40 mg/dL and absence of diabetes or hypertension. The rest of the obesity sample was defined as MCO. MHO or MCO were compared with the rest of the sample, defined as normal weight (NW) individuals. OutcomesClinical, biochemical, erectile, and PCDU assessment in MHO, MCO and NW men in both cohorts; longitudinal MACE incidence assessment in cohort 1. ResultsIn cohort 1, 816 men (16.5%) were obese, 181 (3.7%) were MHO, and 635 (12.8%) were MCO. In cohort 2, 68 men (28.4%) were obese, 19 (8.2%) were MHO, and 49 (21.2%) were MCO. After adjusting for confounders, in both samples, the men with MHO and MCO had lower total testosterone levels and worse PCDU parameters compared with the NW men. However, only MCO men had worse erectile function compared with NW men. In the longitudinal study, both MHO and MCO men independently had a higher incidence of MACE compared with NW men (P < .05 for both). In cohort 2, MHO and MCO men had a larger prostate volume, and MCO men also had higher ultrasound and biochemical (IL-8) features of prostatic inflammation compared with NW men, but no differences in prostatitis-like symptoms or seminal parameters. Clinical implicationsMHO men should be considered at high cardiovascular risk like MCO men and followed-up for erectile dysfunction and prostate abnormalities overtime. Strengths & LimitationsThe study simultaneously examined several endpoints with validated instruments within 2 different male populations, 1 with SD and 1 with infertility. As for limitations, there is no consensus in the scientific community regarding the definition of MHO, and the results are derived from patients with SD or infertility, which could have different characteristics than the general male population. ConclusionMHO is associated with subclinical ED, increased cardiovascular risk, and prostate enlargement.Lotti F, Rastrelli G, Maseroli E, et al. Impact of Metabolically Healthy Obesity in Patients with Andrological Problems. J Sex Med 2019:16;821–832.

Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study

Background and aimsThere is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population. Methods and resultsIn the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5–24.9 kg/m2) or obesity (BMI ≥30.0 kg/m2) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome – waist circumference was not taken into account because of collinearity with BMI.Persons with MHO had a higher prevalence of CAC than metabolically healthy normal weight (MHNW) persons (prevalence ratio = 1.59 (95% confidence interval 1.38–1.84) for the main analysis). Persons with MHO had slightly larger odds of CAC progression than persons with MHNW (odds ratios ranged from 1.17 (0.69–1.99) to 1.48 (1.02–2.13) depending on MHO definition and statistical approach). ConclusionOur analyses on MHO CAC associations add to the evidence that MHO is not a purely benign health condition.

Defining metabolically healthy obesity in children: a scoping review.

We conducted a scoping review to identify definitions of metabolically healthy obesity (MHO), describe gaps in the literature, and establish a universal definition of MHO in children. We searched electronic databases from January 1980 to June 2017 and grey literature. Experimental, quasi-experimental, or observational studies were eligible for inclusion if they (i) included a definition of MHO that identified risk factors, cut-off values, and the number of criteria used to define MHO, and (ii) classified 2-18year olds as overweight or obese. Two reviewers independently screened 1,711 papers for relevance and quality; we extracted data from 39 individual reports that met inclusion criteria. Most (31/39; 79%) definitions of MHO included an absence of cardiometabolic risk factors. Heterogeneity across MHO definitions, obesity criteria, and sample sizes/characteristics resulted in variable prevalence estimates (3-80%). Finally, we convened an international panel of 46 experts to complete a 4-round Delphi process to generate a consensus-based definition of MHO. Based on consensus (≥ 80% agreement), our definition of MHO included: high density lipoprotein-cholesterol > 40mg/dl (or>1.03mmol/l), triglycerides ≤ 150mg/dl (or≤1.7mmol/l), systolic and diastolic blood pressure ≤ 90th percentile, and a measure of glycemia. This definition of MHO holds potential universal value to enable comparisons between studies and inform clinical decision-making for children with obesity.

Prevalence and predictors of metabolically healthy obesity in adolescents: findings from the national \u201cJeeluna\u201d study in Saudi-Arabia

BackgroundObese children and adolescents may vary with respect to their health profile, an observation that has been highlighted by the characterization of metabolically healthy obesity (MHO). The objectives of this study were to examine the prevalence of MHO amongst obese adolescents in Saudi-Arabia, and investigate the anthropometric, socio-demographic, and lifestyle predictors of MHO in this age group.MethodsA national cross-sectional school-based survey (Jeeluna) was conducted in Saudi-Arabia in 2011–2012 (n = 1047 obese adolescents). Anthropometric, blood pressure and biochemical measurements were obtained. A multicomponent questionnaire covering socio-demographic, lifestyle, dietary, psychosocial and physical activity characteristics was administered. Classification of MHO was based on two different definitions. According to the first definition, subjects were categorized as MHO based on the absence of the following traditional cardiometabolic risk (CR) factors: systolic blood pressure (SBP) or diastolic blood pressure (DBP) >90th percentile for age, sex, and height; triglycerides (TG) > 1.25 mmol/L; high density lipoprotein-cholesterol (HDL-C) ≤1.02 mmol/L; glucose ≥5.6 mmol/L. The second definition of MHO was based on absence of any cardiometabolic risk factor, according to the International Diabetes Federation (IDF) criteria.ResultsThe prevalence of MHO ranged between 20.9% (IDF) and 23.8% (CR). Subjects with MHO were younger, less obese, had smaller waist circumference (WC) and were more likely to be females. Based on stepwise logistic regression analyses, and according to the IDF definition, body mass index (BMI) (OR = 0.89, 95% CI: 0.84–0.93) and WC (OR = 0.97, 95% CI: 0.96–0.98) were the only significant independent predictors of MHO. Based on the CR definition, the independent predictors of MHO included female gender (OR = 1.76, 95% CI: 1.29–2.41), BMI (OR = 0.97, 95% CI: 0.94–1.00), and weekly frequency of day napping (OR = 1.06, 95% CI: 1.00–1.12). Analysis by gender showed that vegetables’ intake and sleep indicators were associated with MHO in boys but not in girls.ConclusionThe study showed that one out of five obese adolescents is metabolically healthy. It also identified anthropometric factors as predictors of MHO and suggested gender-based differences in the association between diet, sleep and MHO in adolescents. Findings may be used in the development of intervention strategies aimed at improving metabolic heath in obese adolescents.

Metabolically healthy obesity and cardiovascular events: A systematic review and meta-analysis.

Previous studies have provided inconsistent results about the cardiovascular risks for participants with metabolically healthy obesity (MHO). These uncertainties might partly reflect the lack of a uniform definition of MHO. We conducted a systematic review and meta-analysis to examine whether there is a suitable approach that identifies obese participants who are not at an increased risk of cardiovascular events compared with healthy normal-weight participants. Twenty-two prospective studies were eligible for the meta-analysis. Using random-effect models, pooled relative risks (RRs) were calculated for the combined effects of obesity with the presence or absence of metabolic syndrome, insulin resistance, hypertension, diabetes, hyperlipidaemia and any of these metabolic factors. Participants with MHO defined by the absence of metabolic syndrome were at increased risk for cardiovascular events compared with healthy normal-weight participants (pooled RR 1.45, 95% confidence interval (CI) 1.20-1.70), but had lower risks than unhealthy normal-weight (RR 2.07, 95% CI 1.62-2.65) and obese (RR 2.31, 95% CI 1.99-2.69) participants. The risk associated with participants who had MHO was particularly high over the long term. Similar risk estimates were observed when MHO was defined by other approaches. None of the approaches clearly identified an obese subgroup not at increased risk of cardiovascular events compared with normal-weight healthy participants. A benign obese phenotype might be defined by strict definitions, but insufficient studies exist to support this. More research is needed to better define MHO.

Letter: Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status (Endocrinol Metab2015;30:185-94, Tae Hoon Lee et al.)

Obesity is a major public health problem worldwide, being an important risk factor for the development of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease, consequently increasing all-cause mortality [1]. However, metabolically healthy obesity (MHO), a subtype of obesity, is associated with the absence of metabolic abnormalities such as dyslipidemia, insulin-resistance, and hypertension; all-cause mortality is not elevated [2]. Therefore, it is important to distinguish those with MHO from other obese subjects, and to use a different strategy to treat those with MHO. Lee et al. [3] studied biomarkers that might indicate the status of metabolic health. Serum tumor necrosis factor α (TNF-α) and adipocyte fatty acid binding protein (A-FABP) levels were higher in metabolically unhealthy non-obese subjects than in those with MHO. Although differences between obese groups were not apparent, the work suggested that TNF-α and A-FABP levels might serve as markers of metabolic status. Work on MHO is associated with certain challenges. First, no consensus has yet emerged on how MHO should be defined. Phillips and Perry [4] showed that both the prevalence of MHO and the levels of supposedly relevant inflammatory markers varied when different definitions of MHO were used. Second, although body mass index (BMI) is commonly used to identify obesity, this measure does not discriminate between lean and fat body mass [1]. Velho et al. [5] also found that the prevalence of MHO varied when different criteria were used to define the condition, and when obesity was variously defined by reference to BMI, body fat percentage, and waist circumference. However, the cited authors did evaluate several markers of obesity. Therefore, I wonder whether the authors have explored the possible existence of relationships between adipocytokine levels and MHO using the various MHO criteria (combinations of certain obesity markers). I respectfully suggest that such data could be very useful. In general, a better understanding of the relationships between the levels of certain biomarkers and MHO requires that further longitudinal studies be conducted.

Response: Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status (Endocrinol Metab 2015;30:185-94, Tae Hoon Lee et al.).

First, we wish to express our great thanks to Prof. Kim for choosing our article and for noting an important point in our study. During the past few years, metabolically healthy obesity (MHO) has been a hot topic of debate in the field of obesity because its definition differs slightly from that of metabolic syndrome and because the inclusion of insulin resistance and systemic inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) in its definition is advantageous [1]. However, recently published review articles and meta-analyses have argued against the existence of MHO as a specific phenotype of obesity [2-4]. These review papers are skeptical about the existence of “healthy obesity” in terms of the development of cardiovascular disease, mortality, and diabetes. The reason for this discrepancy could be due to differences in ethnicity or study populations. However, the main reasons are thought to be the absence of a unified definition of MHO and differences in the duration of time that the subjects had been “metabolically healthy” and “obese” among individual studies. A very recent article by Hamer et al. [5] discussed the stability of MHO. They followed 2,422 participants in the English Longitudinal Study of Ageing for a median of 8 years and found that 44.5% of healthy obese people had transitioned into an unhealthy state, compared with only 16.6% and 26.2% of healthy adults of normal weight and overweight adults, respectively. These results suggest that a healthy obese phenotype is relatively unstable. Based on these results, we must consider not only the current status of a patient with MHO, but also how long the patient has had an MHO or obese status; a considerable portion of those with MHO might convert to a metabolically unhealthy obese status during the follow-up secondary to the deleterious effects of obesity itself. In our study published in volume 30, issue 2 of Endocrinology and Metabolism (EnM), we showed that among the adipocytokines measured in our study subjects, high concentrations of tumor necrosis factor α and adipocyte fatty acid binding protein were significantly associated with metabolically unhealthy status in non-obese individuals [6]. Although MHO is being discussed more than other phenotypes, we focused on the concentrations of these adipocytokines in metabolically unhealthy non-obese subjects. Based on the results of our paper, we can assume that increased adipocytokine concentrations serve as an indicator for determining metabolic health in these subjects, as shown in previous studies [7,8]. We recommend the inclusion of these adipocytokine levels in the definition of metabolic health, if possible. Unfortunately, we could not analyze the statistical differences in adipocytokine concentrations according to the different definitions of MHO, such as that including hs-CRP, because

Metabolic and cardiovascular implications of a metabolically healthy obesity phenotype.

Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases.

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used

To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found.