Metabolically Healthy Obesity Status Research Articles

A Bayesian network analysis of the probabilistic relationships between metabolically healthy obesity and cardiovascular disease risk under new diagnostic criteria.

The relationship between metabolically healthy obesity (MHO) and cardiovascular disease (CVD) risk remains debated. The critical point may be the lack of consensus on MHO's definition and diagnostic criteria. This study aimed to investigate the association of MHO status with arteriosclerosis-CVD (ASCVD) risk in Chinese under new diagnostic criteria. Participants aged 35-79 in the 2009 China Health and Nutrition Survey cohort were included. The 10-year ASCVD risk was predicted by the prediction for ASCVD risk in China, and participants with a predicted risk of ⩾ 10% were classified into the high-risk group. The Bayesian network (BN) models were constructed to characterize the multivariable probabilistic connections between metabolically obesity phenotypes and ASCVD risk. The 10-year ASCVD risk score and the proportion of individuals at ASCVD high risk were significantly different between metabolically obesity phenotypes (P< 0.001). BN reasoning results showed that MHO individuals were not significantly associated with a 10-year ASCVD risk. Among metabolically unhealthy individuals, the conditional probability of high ASCVD risk increased with the Body Mass Index (BMI), with the conditional probability of high ASCVD risk was 24.63% (95% CI: 22.81-26.55%), 32.97% (95% CI: 30.75-35.27%) and 40.2% (95% CI: 36.64-43.86%) for metabolically unhealthy normal weight (MUNW), metabolically healthy overweight weight (MHOW), and metabolically unhealthy obesity (MUO) group, respectively. Subgroup analysis showed that MHO individuals were at increased risk of CVD compared with metabolically healthy normal weight (MHNW) individuals only in females. These results showed that there was no significant increase in ASCVD risk of MHO phenotype based on the new diagnostic criteria, suggesting that MHO is in a relatively healthy state.

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study.

Obesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry. A total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO). MHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders. In AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes.

ASSOCIATION OF TRANSITION IN METABOLIC HEALTH AND OBESITY WITH AGE AT ONSET FOR INCIDENT CARDIOVASCULAR DISEASES

Objective: The cardiometabolic risk associated with metabolically healthy obesity (MHO) remains the subject of debate. It is unclear whether changes in MHO status affect premature cardiovascular disease (CVD) risk. In this study, we aimed to investigate the association of MHO and its transition over time with incident CVD by age at onset. Design and method: In a community-based prospective cohort study, 54441 adults who were free of CVD in or before 2010 were followed up for incident CVD until 2020. Four age groups were examined (&lt;55, 55-65, 65-75, and &gt; = 75 years) for CVD onset. In each age group, participants were cross-classified by BMI categories and metabolic health. The Cox proportional hazards model with age as the underlying time scale was used to examine the associations of metabolic health status and its transition with CVD across BMI categories. Results: During a median follow-up of 9.59 years, 3038 participants developed CVD. Individuals with metabolic unhealthy obesity (MUO) had the highest hazard ratio (HR) for CVD onset at any age, ranging from 2.68 (95% CI, 2.02-3.55) for CVD onset in those younger than 55 years to 1.55 (95% CI, 1.09-2.10) for CVD onset in those older than 75 years. Individuals who were MHO at baseline or even remained metabolically healthy were still at increased risk of premature CVD, and the association attenuated with increasing onset age. Conclusions: In this cohort study, the association between metabolically healthy and obesity status and incident CVD appeared to differ by age at CVD onset and the associations were more evident for premature onset of CVD.

Abstract P064: Metabolic Risk Transitions In Obesity With The Incidence Of Heart Failure And Coronary Heart Disease: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Obesity is associated with a varying spectrum of metabolic risk, from the metabolically healthy obesity (MHO) phenotype, to metabolically unhealthy obesity (MUO) with the development of metabolic syndrome (MetS) and diabetes (DM). The longitudinal association of metabolic risk with CVD phenotypes (CHD, HF) has not been well characterized. Hypothesis: Persistent MHO is independently associated with heart failure (HF) but not coronary heart disease (CHD), and regression from MUO to MHO mitigates CVD risk. Methods: We conducted a prospective analysis of 10,011 Visit 4 (1996-98) ARIC participants free of HF and CHD (mean age 63, 21% Black, 56% female). Metabolic risk among those with obesity (BMI ≥ 30 kg/m 2 ) was categorized as MHO (no MetS or DM), MUO (MetS present) and MUO with DM, with same categorizations among those without obesity. We used Cox regression models to estimate associations of cross-categories of metabolic risk status at Visit 2 (1990-92) and Visit 4 with risk of HF and CHD after Visit 4 through 12/21/19. (Reference: persistent metabolically healthy normal weight). Results: Between Visits 2 and 4, 56% of those with MHO transitioned to MUO. There were 2212 HF and 1648 CHD events, median follow-up of 20.5 years. Persistent MHO status was associated with increased risk for HF (HR:1.59, 95% CI: 1.19-2.13) but not CHD (HR: 1.08, 95% CI: 0.74-1.58) (Table). Persistent MUO with DM had the highest risk for HF (HR: 5.30, 95% CI: 4.38-6.41) and CHD (HR: 3.77, 95% CI: 3.00-4.74). Among those with MUO at Visit 2, progression to MUO with DM at Visit 4 was linked to greater risk for HF and CHD, while regression to MHO was associated with an attenuated risk for CVD. Similar patterns were seen for those without obesity (data not shown). Conclusions: Transitions in metabolic risk status are common and associated with divergent patterns of CVD risk. Progression from MHO to MUO and even persistent MHO are linked to HF risk, whereas regression from MUO to MHO may attenuate CVD risk. Primordial prevention of obesity is warranted to stave off HF.

Metabolically healthy obesity in children enrolled in the CANadian Pediatric Weight management Registry (CANPWR): An exploratory secondary analysis of baseline data.

Our study purpose was to determine the prevalence of metabolically healthy obesity (MHO) and examine factors associated with MHO in children with obesity. This cross-sectional study was a secondary, exploratory analysis of data that included 2-17 years old with a body mass index (BMI) ≥85th percentile from the CANadian Pediatric Weight management Registry. Children were classified as having MHO or metabolically unhealthy obesity (MUO) using consensus-based criteria. Those with MHO had normal triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Logistic regression was used to examine factors associated with MHO, which included calculating odds ratios (ORs) and 95% confidence intervals (CIs). In total, 945 children were included (mean age: 12.3 years; 51% female). The prevalence of MHO was 31% (n= 297), with lower levels across increasing age categories (2-5 years [n= 18; 43%], 6-11 years [n= 127; 35%], 12-17 years [n= 152; 28%]). Children with MHO were younger, weighed less, and had lower BMI z-scores than their peers with MUO (all p< 0.01). MHO status was positively associated with physical activity (OR: 1.18; 95% CI: 1.01-1.38), skim milk intake (OR: 1.10; 95% CI: 1.01-1.19), and fruit intake (OR: 1.12; 95% CI: 1.01-1.24) and negatively associated with BMI z-score (OR: 0.69; 95% CI: 0.60-0.79), total screen time in hours (OR: 0.79; 96% CI: 0.68-0.92), and intake of fruit flavoured drinks (OR: 0.91; 95% CI: 0.84-0.99). These findings may help guide clinical decision-making regarding obesity management by focusing on children with MUO who are at relatively high cardiometabolic risk.

1650-P: Metabolically Healthy Obese Status and Incident Dementia Events among 5.7 Million Elderly People

Background: Obese individuals with normal metabolic profiles, so-called “metabolically healthy obese (MHO)” status has shown better clinical outcomes via previous studies. However, studies dealing with the association between MHO and dementia, which is deeply associated with metabolic disorders, were still insufficient. We designed this study to assess the association between MHO and the risk of incident dementia. Methods: The present study is a retrospective cohort study, including 5,669,488 patients aged 60 years old or over without any history of dementia, by using the National Health Insurance System of South Korea. Subjects were divided into 4 groups based on their metabolic health and obesity status. Metabolic health was determined based on the criteria of metabolic syndrome by Adult Treatment Panel-III. Obesity was judged based on the baseline body mass index. The incidence of dementia was checked and compared longitudinally between 4 groups. Results: When we put the metabolically healthy non-obese group to the reference value (hazard ratio (HR) = 1), MHO group showed the lowest incidence of dementia (HR 0.87, 95% confidence interval (CI) 0.86-0.88). This trend was more prominent when we followed up the risk of Alzheimer’s disease as a subgroup analysis (HR 0.85, 95% CI 0.83-0.86). Non-obese subjects with metabolic syndrome showed significantly increased risk for overall dementia (HR 1.20, 95% CI 1.19-1.21), especially for vascular dementia (HR 1.41, 95% CI 1.38-1.45). Conclusion: MHO status was associated with lower risk for dementia, especially for Alzheimer’s disease. Disclosure J. Bae: None. J. Lee: None. Y. Cho: None. M. Lee: None. S. Lee: None. I. Lee: None. E. Kang: None. S.J. Cho: None. K. Han: None. B. Cha: None. Y. Lee: None.

Transition from metabolically benign to metabolically unhealthy obesity and 10-year cardiovascular disease incidence: The ATTICA cohort study

Background/ObjectivesMetabolically benign obesity remains a scientific field of considerable debate. The aim of the present work was to evaluate whether metabolically healthy obese (MHO) status is a transient condition which propagates 10-year cardiovascular disease (CVD) onset. MethodsA prospective longitudinal study was conducted during 2001–2012, the ATTICA study studying 1514 (49.8%) men and 1528 (50.2%) women (aged >18 years old) free of CVD and residing in the greater Athens area, Greece. Follow-up assessment of first combined CVD event (2011−2012) was achieved in n = 2020 participants; of them, 317 (15.7%) incident cases were identified. Obesity was defined as body mass index ≥30 kg/m2 and healthy metabolic status as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). ResultsThe MHO prevalence was 4.8% (n = 146) with 28.2% of obese participants presenting metabolically healthy status at baseline. Within this group, 52% developed unhealthy metabolic status during the 10-year follow up. MHO vs. metabolically healthy non-obese participants had a higher likelihood of presenting with 10-year CVD events, yet only the subset of them who lost their baseline status reached the level of significance (Hazard Ratio (HR) = 1.43, 95% Confidence Interval (95% CI) 1.02, 2.01). Sensitivity analyses revealed that MHO status was independently associated with elevated CVD risk in women and participants with low adherence to the Mediterranean diet, low grade inflammation, and insulin resistance. ConclusionsMHO status is a transient condition where weight management is demanded to prevent the establishment of unhealthy cardiometabolic features. The existence of obese persons who remain “longitudinally” resilient to metabolic abnormalities is an emerging area of future research.

Duration and stability of metabolically healthy obesity over 30 years.

Background:Obese adults who free from metabolic risk factors may develop risk factors over time. Our objective was to characterize development of obesity and duration of metabolically-healthy-obese (MHO) over 30 years.Methods:Participants in CARDIA who developed obesity (BMI ≥ 30 kg/m2) at follow up exams 7, 10, 15, 20, 25 and 30 were analyzed. MHO was defined as obese and having 0 or 1 risk factor: ≥SBP/DBP 130/85mmHg; fasting glucose ≥100mg/dL/5.55mmol/L; fasting triglycerides (≥150 mg/dL/1.69mmol/L); and HDL-C (men <40mg/dL/1.036mmol/L, women <50mg/dL/1.295mmol/L) or on any medication(s) for these conditions. MHO duration (yrs) and obesity duration (yrs) were estimated for each subsequent time-point; and an overall cumulative duration was also calculated over available follow-up. MHO duration (%) was approximated as MHO duration ÷ obesity duration. Stable MHO was defined as 100% MHO duration over follow-up, while transient MHO was defined as <1–99%. Chi-squared tests were used to compare proportions by sex and race across obesity phenotypes. Multivariable adjusted ANCOVA adjusting for baseline BMI, age, race, sex, and was used to analyze obesity duration in all individuals who developed obesity, and also compare MHO duration (%) across race and sex in transient MHO individuals.Results:Of the 987 eligible participants who developed obesity, 51% were African American (AA), 56% were women. Higher percentages of AA were classified as transient MHO, and higher proportions of females were MHO (both p<0.0001). Obesity duration (yrs) was higher in transient MHO compared with stable MHO (mean difference: 6.2 ± 0.5 yrs, p<0.0001). Of those with transient MHO, African Americans (51.4 ± 1.6%) were more likely to have longer MHO duration compared to Caucasians (44.4 ± 1.9%, p=0.005).Conclusion:MHO status can be a transient phenotype which differs by sex and race. Future studies are needed to explore modifiable lifestyle/behavioral predictors associated with longer MHO duration.

Influence of Obesity and Metabolic Abnormalities on the Risk of Developing Colorectal Neoplasia.

Obesity and metabolic syndrome are risk factors for colorectal neoplasia (CRN). However, the association between metabolically healthy obese (MHO) or metabolically unhealthy non-obese (MUNO) status and the risk of CRN remains unclear. We aimed to elucidate the association between MHO or MUNO status and the risk of CRN. A total of 139,023 asymptomatic subjects who underwent a primary screening colonoscopy were categorized into 4 groups according to obesity and metabolic status: metabolically healthy non-obese (MHNO), MHO, MUNO, and metabolically unhealthy obese (MUO). Mean participant age was 41.0years, and the proportion of men was 65.3%. Among men, the risk of overall CRN increased in MHO (adjusted odds ratio [AOR] 1.22, 95% confidence intervals [CI] 1.12-1.33), MUNO (AOR 1.25, 95% CI 1.18-1.31), and MUO groups (AOR 1.47, 95% CI 1.40-1.54) compared with the MHNO group, whereas the risk of advanced CRN (ACRN) increased in MUNO (AOR 1.16, 95% CI 1.002-1.33) and MUO groups (AOR 1.49, 95% CI 1.31-1.70), but not in the MHO group (AOR 0.92, 95% CI 0.70-1.21). Moreover, among non-obese men, the risk of overall CRN and ACRN linearly increased with an increasing number of metabolic abnormalities. However, among women, only the MUO group had an increased risk of overall CRN (AOR 1.34, 95% CI 1.21-1.47) and no other significant associations were observed. Poor metabolic health, regardless of obesity, is an independent risk factor for CRN in men. Our results suggest that men with metabolic abnormalities should be considered as a high-risk group for colorectal cancer, even if they are not obese.

Outdoor Time and Metabolically Healthy Obesity in Children

A large proportion of children are recognized as metabolically healthy obese (MHO) and present a favorable cardio-metabolic profile. However, the contribution of outdoor time physical activity (PA) to the MHO phenotype is unknown. PURPOSE: To investigate the association between outdoor time PA and the MHO phenotype in children. METHODS: An analysis of overweight and obese children aged 6-14 (n=386) from the Canadian Health Measures Survey (cycles 3-4) was performed. Outdoor time PA (hours/week) was self-reported using a series of questions in relation to the school schedule, such as: “during the past month, on an average school day, how much time did you usually spend outside?” Participants were given a score of 0-5 based on their response: 0 min. (0); 1 to <15 mins. (1); 15 to <30 mins. (2); 30 to <1 hour (3); 1 to <2 hours (4); and ≥2 hours (5). Then, a computed score, ranging from 0-25, was created for outdoor time PA. MHO status was determined based on the absence of cardio-metabolic risk factors including: triglycerides, HDL-cholesterol, systolic or diastolic blood pressure, and glucose (MHO: 0 cardio-metabolic risk factors; non-MHO: ≥1 cardio-metabolic risk factors). Multiple logistic regression analyses for the likelihood of MHO were adjusted for age, sex, socioeconomic status, and moderate-to-vigorous PA (MVPA) intensity. RESULTS: The proportion of MHO children was 58.5%. No significant differences were observed between MHO and non-MHO according to outdoor time PA, sedentary time, or MVPA (p>0.05). Logistic regressions indicated that outdoor time PA was not significantly associated with the MHO phenotype (OR: 0.99, 95% CI=0.92-1.05; p=0.69), while MVPA was significantly associated with the MHO phenotype (OR: 1.01, 95% CI=1.00-1.02; p=0.03). CONCLUSIONS: Outdoor time PA is not associated with the MHO phenotype. Children are more likely to be MHO with greater amounts of MVPA, regardless of whether these activities are completed outdoors or indoors.

Whole-genome transcriptomic insights into protective molecular mechanisms in metabolically healthy obese African Americans

Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO). Unbiased transcriptome-wide network analysis was carried out to identify molecular modules of co-expressed genes that are collectively associated with MHO. Network analysis identified a group of 23 co-expressed genes, including ribosomal protein genes (RPs), which were significantly downregulated in MHO subjects. The three pathways enriched in the group of co-expressed genes are EIF2 signaling, regulation of eIF4 and p70S6K signaling, and mTOR signaling. The expression of ten of the RPs collectively predicted MHO status with an area under the curve of 0.81. Triglycerides/HDL (TG/HDL) ratio, an index of insulin resistance, was the best predictor of the expression of genes in the MHO group. The higher TG/HDL values observed in the MAO subjects may underlie the activation of endoplasmic reticulum (ER) and related-stress pathways that lead to a chronic inflammatory state. In summary, these findings suggest that controlling ER stress and/or ribosomal stress by downregulating RPs or controlling TG/HDL ratio may represent effective strategies to prevent or delay the occurrence of metabolic disorders in obese individuals.

Abstract 10: Metabolically Healthy Obesity Over 25 Years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study: Race and Sex Differences

Background: Obesity is heterogeneous condition with phenotypic variation. Metabolically healthy obese (MHO) may represent an unstable phenotype which changes over time. MHO duration, or the length of time in MHO, is not well characterized. The purpose is to quantify MHO duration over 25 years and explore possible race/sex differences. Methods: Young adults (baseline ages 18-30 yrs) from CARDIA were included if they were non-obese at baseline, developed obesity (BMI ≥30kg/m 2 ) at any follow-up exam (yrs 7, 10, 15, 20 and 25), and had complete data for metabolic status, age, race and sex (n=702). MHO was defined as obese (BMI ≥30 kg/m 2 ) and having either 0 or 1 risk factor of the following: ≥SBP/DBP 130/85 mmHg; glucose ≥100 mg/dL; triglycerides (≥150 mg/dL); and HDL-C (men &lt;40, women &lt;50 mg/dL). Obese individuals with ≥2 risk factors were classified as metabolically unhealthy obese (MUO). MHO duration (yrs) and obesity duration (yrs) were estimated for subsequent time-points; and a duration sum was calculated for the follow-up period. For two time-points in which a person remained MHO and obese, a duration for that period was assigned. If they transitioned to MUO or non-obese, then the midpoint of the time period was estimated as MHO duration (yrs). MHO duration was also expressed as the percentage (%) of the total obesity duration. Multivariable adjusted ANCOVA was used to compare MHO duration (%) between race and sex groups (black men, white men, black women and white women), adjusting for baseline age, baseline BMI status (normal weight or overweight). Results: The eligible CARDIA sample was 55% black, 71% women and had a mean (± SD) baseline age of 25.0 ± 3.7 yrs. Duration of obesity was 12.3 ± 6.8 yrs, MHO duration (yrs) was 6.2 ± 5.4 yrs (range: 0 years to 19 yrs), and MHO duration (%) was 51.9 ± 34.8%. After adjusting for age and baseline BMI, MHO duration (%, mean ± SE) was significantly higher in women compared to men within race (black women n=292: 56.3 ± 2.0% vs. black men n=91: 43.3 ± 3.6%, p=0.001; white women n=206: 56.1 ± 2.4% vs. white men n=113: 39.7 ± 3.2%, p &lt;0.0001). No significant differences were found between race groups within gender (black men vs. white men or black women vs. white women). Conclusion: MHO status is a transient phenotype accounting for only approximately half of obesity duration. Women have longer MHO duration compared to men, but differences by race were not apparent. Future research is needed to explore possible modifiable predictors and/or determinants of longer MHO duration in order to maintain a healthy cardiometabolic phenotype, even in the presence of obesity.

LBPS 01-06 GENETIC AND ENVIRONMENTAL FACTORS OF METABOLICALLY HEALTHY OBESITY IN CHINESE CHILDREN

Objective: The metabolically healthy obesity (MHO), a sub-phenotype of obesity with a favorable metabolic profile, has been the focus of recent research interest. But the potential role of genetic predisposition or lifestyle factors in the MHO phenotype is yet to be clarified. We aimed to investigate the impact factors of MHO status in Chinese children. Design and Method: 1790 overweight and obese children aged 6–18 years old were included in this study. Participants were classified as MHO or metabolically unhealthy obesity (MUO) based on insulin resistance (IR) or cardio-metabolic risk (CR) factors (blood pressure, lipids and glucose). 28 genetic variants previously reported from GWAS on obesity, hypertension and dyslipidemia were genotyped. The environmental factors of lifestyle, socio-economic status and birth weight were assessed by questionnaire. Overweight and obesity were defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force. Age, sex, tanner stage and residence were adjusted for covariates. Results: The prevalence of MHO-IR and MHO-CR were 60.7% and 30.7%, respectively. Proportion of severe obesity and central obesity and levels of BMI and WC were lower in MHO children compared with MUO children regardless of definitions. In addition to BMI and WC, the frequency of meat and fruit consumption, GNPDA2- rs10938397 and KCTD15-rs29941 were independent predictors of MHO-IR, whereas the frequency of meat consumption, FTO -rs9939609, and CYP17A1- rs11191548 were independent predictors of MHO-CR. Conclusions: At least one-third of Chinese obese children can be classified as MHO. Both genetic predisposition and environment factors contribute to the prediction of MHO status.

Risk of the Development of Diabetes and Cardiovascular Disease in Metabolically Healthy Obese People: The Korean Genome and Epidemiology Study.

The reported effects of a metabolically healthy obese (MHO) phenotype on diabetes and cardiovascular disease (CVD) risk are contradictory. Within the context of a population-based cohort study, we aimed to investigate the long-term risk of an MHO status for the development of diabetes and CVD, and whether consistency of this phenotype or age affected cardiometabolic outcomes.We recruited 7588 subjects without diabetes or CVD, aged 40 to 69 years at baseline examination, from the Korean Genome and Epidemiology Study, and followed-up these subjects for 10 years biennially. Participants were divided into 4 groups based on the body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). We defined persistent phenotypes if subjects maintained the same phenotype at every visit from baseline to their last visit. Incident diabetes and CVD morbidity or mortality were identified during 10 years of follow-up.Compared to MHNW controls, MUNW and MUO groups had increased risk for development of diabetes (hazard ratio [HR] 3.0 [95% CI: 2.5–3.6], and 4.0 [3.4–4.7], respectively) and CVD (HR 1.6 [1.3–2.0], and 1.9 [1.5–2.4], respectively). However, the MHO group showed only a marginal increase in risk for diabetes and CVD (HR 1.2 [0.99–1.6], 1.4 [0.99–1.8], respectively). The impact of MHO on the development of diabetes was more prominent in younger individuals (HR 1.9 [1.2–3.1] vs 1.1 [0.8–1.4], <45 years vs ≥45 years at baseline). Only 15.8% of MHO subjects maintained the MHO phenotype at every visit from baseline to the 5th biennial examination (persistent MHO). In subjects with persistent MHO, the risk for diabetes and CVD was significantly higher than those with persistent MHNW (1.9 [1.2–3.1], 2.1 [1.2–3.7], respectively).MHO phenotype, even if maintained for a long time, was associated with a significantly higher risk for the development of diabetes and CVD in Korean subjects.

Identification of Genetic and Environmental Factors Predicting Metabolically Healthy Obesity in Children: Data From the BCAMS Study.

Available data related to the metabolically healthy obesity (MHO) phenotype are mainly derived from studies in adults because studies during childhood are very limited to date. The objective of the study was to determine the prevalence of MHO in Chinese children and to investigate environmental and genetic factors impacting on MHO status. This was a cross-sectional study. A total of 1213 children with a body mass index at the 95th percentile or greater aged 6–18 years were included in this study. Participants were classified as MHO or of metabolically unhealthy obesity based on insulin resistance (IR) or cardiometabolic risk (CR) factors (blood pressure, lipids, and glucose). Twenty-two genetic variants previously reported from genome-wide association studies of obesity and diabetes plus the environmental factors of lifestyle, socioeconomic status, and birth weight was assessed. The prevalence of MHO-IR and MHO-CR were 27.1% and 37.2%, respectively. Waist circumference was an independent predictor of MHO, regardless of definitions, whereas walking to school and KCNQ1-rs2237897 were independent predictors of MHO-CR. Acanthosis nigricans, birth weight, the frequency of soft drink consumption, the mother's education status, and KCNQ1-rs2237892 were independent predictors of MHO-IR. Multiplicative interaction effects were found between KCNQ1-rs2237897 and walking to school on MHO-CR (odds ratio 1.31 [95% confidence interval 1.05–1.63]) and between rs2237892 and consumption of soft drinks on MHO-IR (odds ratio 0.80 [95% confidence interval 0.68–0.94]). Approximately one-third of Chinese obese children can be classified as MHO. Both genetic predisposition and environment factors and their interaction contribute to the prediction of MHO status. This study provides novel insights into the heterogeneity of obesity and has the potential to impact the optimization of the intervention options and regimens in the management of pediatric obesity.

Variations in the prevalence and predictors of prevalent metabolically healthy obesity in adolescents.

Obesity is a heterogeneous condition, which includes a subset of individuals that can be classified as having metabolically healthy obesity (MHO), but there is no consensus on what constitutes MHO. Thus, the objective of the study is to examine the prevalence and predictors of prevalent MHO in adolescents using various definitions of MHO. Cross-sectional data from the 1999-2010 National Health and Nutrition Examination Surveys were used. Participants included 316 male and 316 female adolescents aged 12-19 years with a BMI ≥ 95th percentile. Two definitions were used to define MHO. First, MHO was defined as having ≤1 metabolic syndrome criteria (excluding waist) and being free of type 2 diabetes, hypertension and dyslipidemia. Second, MHO was defined as being free of all metabolic syndrome criteria, insulin resistance and inflammation. The prevalence of MHO was 42% (male) and 74% (female) using the first definition and 7% (male) and 12% (female) using the second more conservative definition. Lower abdominal obesity (waist circumference) and lower insulin resistance predicted prevalent MHO in male and female adolescents for both definitions (p < 0.01). Associations between dietary components and MHO were weak and inconsistent, while physical activity and inflammation were not associated with MHO in male and female adolescents for both definitions (p > 0.05). The prevalence of MHO in adolescents varied across definitions, with lower levels of abdominal obesity and insulin resistance as the most consistent predictors of prevalent MHO status.

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

Predictors of Metabolically Healthy Obesity in Children

To determine the prevalence of metabolically healthy obesity (MHO) in children and examine the demographic, adiposity, and lifestyle predictors of MHO status. This cross-sectional study included 8-17 year olds with a BMI ≥85th percentile who were enrolled in a multidisciplinary pediatric weight management clinic from 2005-2010. Demographic, anthropometric, lifestyle, and cardiometabolic data were retrieved by retrospective medical record review. Participants were dichotomized as either MHO or metabolically unhealthy obese (MUO) according to two separate classification systems based on: 1) insulin resistance (IR) and 2) cardiometabolic risk (CR) factors (blood pressure, serum lipids, and glucose). Multivariable logistic regression was used to determine predictors of MHO using odds ratios (ORs) with 95% CIs. The prevalence of MHO-IR was 31.5% (n = 57 of 181) and MHO-CR was 21.5% (n = 39 of 181). Waist circumference (OR 0.33 [95% CI 0.18-0.59]; P = 0.0002) and dietary fat intake (OR 0.56 [95% CI 0.31-0.95]; P = 0.04) were independent predictors of MHO-IR; moderate-to-vigorous physical activity (OR 1.80 [95% CI 1.24-2.62]; P = 0.002) was the strongest independent predictor of MHO-CR. Up to one in three children with obesity can be classified as MHO. Depending on the definition, adiposity and lifestyle behaviors both play important roles in predicting MHO status. These findings can inform for whom health services for managing pediatric obesity should be prioritized, especially in circumstances when boys and girls present with CR factors.