METABOLICALLY HEALTHY OBESE INDIVIDUALS HAVE DECREASED HEART FAILURE RISK COMPARED TO NORMAL-WEIGHT PEOPLE IN A SIX-YEAR MEDITERRANEAN STUDY

There is conflicting evidence regarding the association between metabolically healthy obese (MHO) and metabolically unhealthy normal weight (MUNW) with incident hypertension and type 2 diabetes. The role of cardiorespiratory fitness on these associations has not been fully explored. We tested the hypothesis that obesity phenotypes predict incident hypertension and type 2 diabetes, but cardiorespiratory fitness modifies these associations in a prospective study of apparently healthy men. 3800 men (mean age 48±6 yrs, range 20-76 yrs) participated in two health examinations during 1998-2009. All subjects were free of hypertension and type 2 diabetes at baseline examination. MHO was defined as obesity (body mass index ≥ 25 kg/m2) with no more than one metabolic abnormality, and MUNW was defined as body mass index < 23 kg/m2) with two or more abnormalities. Cardiorespiratory fitness was directly measured by peak oxygen uptake during a treadmill test. Incident hypertension and type 2 diabetes were defined as blood pressure ≥140/90mmHg and as ≥6.5% of HbA1c or ≥126mg/dl of fasting glucose at second examination, respectively. During an average follow-up of 5 years (1-12 yrs), there were 371 (9.8%) men incident hypertension and 170 (4.5%) men incident type 2 diabetes. MHO and MUNW were present in 844 (22%) and 249 (6.6%) men. Compared with metabolically healthy normal weight men, MHO and MUNW men were at increased risk for hypertension (relative risk (RR) =1.82, 95% Confidence Interval (CI): 1.29-2.56 and 1.75, 1.11-2.74) and type 2 diabetes (RR=3.68, 1.92-7.07 and 5.35, 2.61-10.94), respectively. These risks in MHO and MUNW men were still persisted with adjustment for confounder variables and cardiorespiratory fitness (hypertension=1.57, 1.05-2.34 and 1.59, 1.01-2.51; type 2 diabetes=3.35, 1.63-6.89 and 4.76, 2.32-9.77). Metabolically healthy obese or metabolically unhealthy normal weight men were at increased risk of hypertension and type 2 diabetes compared with metabolically healthy normal weight men. However, these associations were not attenuated by cardiorespiratory fitness or other confounder factors.

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Integrating Publicly Available Genome-Wide Association Data to Study the Genetic Basis of Metabolically Healthy Obese and Metabolically Obese but Normal-Weight Individuals

Diabetes ◽

10.2337/db14-1358 ◽

2014 ◽

Vol 63 (12) ◽

pp. 4004-4007 ◽

Cited By ~ 9

Author(s):

R. J. F. Loos

Keyword(s):

Genetic Basis ◽

Normal Weight ◽

Genome Wide Association ◽

Metabolically Healthy Obese ◽

Genome Wide ◽

Healthy Obese ◽

Metabolically Healthy ◽

Association Data

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Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals

The FASEB Journal ◽

10.1096/fj.14-263913 ◽

2014 ◽

Vol 29 (3) ◽

pp. 748-758 ◽

Cited By ~ 66

Author(s):

Flavia Badoud ◽

Maude Perreault ◽

Michael A. Zulyniak ◽

David M. Mutch

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Normal Weight ◽

Metabolically Healthy Obese ◽

Healthy Obese ◽

Metabolically Healthy

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Abstract 163: The Prevalence of the Metabolically Healthy Obese Phenotype in an Aging Population and its Association with Subclinical Cardiovascular Disease: The Brazilian Study on Healthy Aging

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a163 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Lara L Roberson ◽

Shozab A Siddiqui ◽

Michael J Blaha ◽

Arthur A Agatston ◽

Roger S Blumenthal ◽

...

Keyword(s):

Cardiovascular Disease ◽

Waist Circumference ◽

Healthy Aging ◽

Subclinical Atherosclerosis ◽

Aging Population ◽

Normal Weight ◽

Metabolically Healthy Obese ◽

Subclinical Cardiovascular Disease ◽

Healthy Obese ◽

Metabolically Healthy

BACKGROUND Obese and overweight individuals have been shown to be at higher risk of CVD events than normal weight individuals. Current literature has elucidated a new phenotype, Metabolically Healthy Obese (MHO), with risks of CVD similar to that of normal weight individuals. Few studies have examined the MHO phenotype in an aging population, especially in association with subclinical cardiovascular disease. METHODS The cross sectional study population consisted of 208 individuals (79% Female), age 80 and older (mean age 84±4, range 80-102). Anthropometrics & biochemical parameters were measured. The Adult Treatment Panel definition of metabolic syndrome (MetS), excluding waist circumference, criteria was used to define metabolically healthy (<3 MetS components) versus unhealthy. A combination of BMI and waist circumference were used to define normal weight and overweight/obese. Multidetector-row cardiac CT for coronary artery calcium score (CACS) was used to detect subclinical atherosclerosis. High reactive C reactive protein (hs-CRP) was measured to assess degree of underlying inflammation. RESULTS The prevalence of MHO defined by BMI≥25 kg/m2 &/or waist circumference >88cm in women, >102cm in men & having 3mg/dl, Uric Acid >6 mg/dl (p=NS). Gender, total cholesterol, HDL, LDL, triglycerides, and SBP was significantly associated with MHO (p<0.05). CONCLUSIONS Our results suggest that the MHO phenotype is still seen in octogenarians, but at lower rates than in the general population suggesting MHO may not simply be an intermediary stage, driven by length of spent in the obese state. Those with this phenotype tended to have lower triglycerides, higher HDL, and lower body fat % than their metabolically at risk obese counterparts (p<0.05), however, degree of subclinical CVD was not different. Further studies are needed to explore the related risk of CVD among MHO octogenarians.

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The role of the gut microbiota on the metabolic status of obese children

Microbial Cell Factories ◽

10.1186/s12934-021-01548-9 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xin Yuan ◽

Ruimin Chen ◽

Kenneth L. McCormick ◽

Ying Zhang ◽

Xiangquan Lin ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota ◽

Normal Weight ◽

Chinese Children ◽

Metabolic Status ◽

Alpha And Beta Diversity ◽

Metabolically Healthy Obese ◽

Tnf Α ◽

Healthy Obese ◽

Metabolically Healthy

Abstract Background The term “metabolically healthy obese (MHO)” denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator. Objective This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic statuses, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6, TNF-α, lipopolysaccharide-binding protein (LBP), and a cytokine up-regulator and mediator, leptin. Results Based on weight and metabolic status, the 86 Chinese children (ages 5–15 years) were divided into three groups: metabolically healthy obese (MHO, n = 42), metabolic unhealthy obese (MUO, n = 23), and healthy normal weight controls (Con, n = 21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO group, Spearman’s correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, LBP was positively correlated with genus Roseburia and Faecalibacterium, and negatively correlated with genus Lactobacillus, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p < 0.05). Conclusion Although there are distinct differences in the characteristic gut microbiota of the MUO population versus MHO, dysbiosis of gut microsystem is already extant in the MHO cohort. The abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds, suggesting that dysbiosis of gut microbiota, present in the MHO children, conceivably serves as a compensatory or remedial response to a surfeit of nutrients.

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Prevalence and characteristics of metabolically healthy obese and metabolically abnormal normal-weight Spanish individuals. The IMAP Study

Primary Care Diabetes ◽

10.1016/j.pcd.2012.10.044 ◽

2013 ◽

Vol 7 (1) ◽

pp. 71

Author(s):

M.R. Bernal-López ◽

F. Miralles-Linares ◽

J. Wärnberg ◽

J. Mancera-Romero ◽

A.J. Baca-Osorio ◽

...

Keyword(s):

Normal Weight ◽

Metabolically Healthy Obese ◽

Healthy Obese ◽

Metabolically Healthy

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Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population

Scientific Reports ◽

10.1038/s41598-021-81940-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jae-Min Park ◽

Da-Hyun Park ◽

Youhyun Song ◽

Jung Oh Kim ◽

Ja-Eun Choi ◽

...

Keyword(s):

Genetic Architecture ◽

Association Studies ◽

Epidemiological Data ◽

Normal Weight ◽

Korean Population ◽

Genome Wide Association Studies ◽

Metabolically Healthy Obese ◽

Genome Wide ◽

Healthy Obese ◽

Metabolically Healthy

AbstractUnderstanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes—metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.

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P5294Metabolically healthy obese is associated with better left atrial function and lower risk of adverse cardiovascular events including atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehz746.0265 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

Y H Lai ◽

Y M Liu ◽

M E Liu ◽

C H Su ◽

H I Yeh ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Strain Rate ◽

Left Atrial ◽

Cardiovascular Events ◽

Global Longitudinal Strain ◽

Normal Weight ◽

Targeted Interventions ◽

Healthy Obese ◽

Metabolically Healthy

Abstract Purpose Metabolic syndrome (MetS) and obesity are both crucial risk factors for heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). However, the prognostic value of utilizing left atrial (LA) deformation imaging in metabolically healthy obese (MHO) or metabolically unhealthy normal weight (MUNW) subjects remains largely unexplored. Methods Speckle-tracking echocardiography was used to evaluate LA strain and strain rate among 3,915 subjects free from clinical heart failure (mean age: 50.0±10.6 years, 66.2% male) undergoing annual cardiovascular health survey. Metabolically unhealthy was defined by the presence of at least one MetS component or history of cardiovascular disease. Participants were categorized as: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy overweight/obese (MUO). Results Markedly decreased LA strain, early-diastolic LA strain rate and increased LA stiffness were observed with metabolic disorders (all trend p: <0.05). During a median follow-up period of 3.68 years, significantly higher risk of primary endpoints (death, heart failure, major cardiovascular events) was observed in MUO vs. MHO (HR=1.87, p=0.005) and MUNW vs. MHNW (HR=2.82, p=0.004). Similar patterns with incident AF (MUO vs MHO: HR=3.05, p=0.001, MUNW vs MHNW: HR=4.04, p=0.002) were also observed. After multivariate adjustment, risk of AF remained associated with low LA strain (β=−0.07, p<0.001), systolic LA strain rate (β:−0.05, p=0.007) and high LA stiffness (β=0.18, p<0.001). Comparison between metabolic groups MHNW (N=1107) MUNW (N=255) p (MUNW vs MHNW) MHO (N=1859) MUO (N=694) p (MUO vs MHO) Age 48±10.57 54.29±11.52 <0.001 49±10.02 54.21±10.49 <0.001 LA GLS (%) 40.6±7.68 37.16±7.5 <0.001 36.77±7.66* 33.58±8.01‡ <0.001 LA SRs 1.79±0.41 1.76±0.48 NS 1.63±0.39* 1.55±0.41‡ <0.001 LA SRe 2.11±0.62 1.8±0.63 <0.001 1.68±0.55* 1.48±0.52‡ <0.001 LA stiffness 0.17±0.08 0.22±0.12 <0.001 0.21±0.11* 0.25±0.13‡ <0.001 *p<0.001 for MHO vs MHNW, ‡p<0.001 for MUO vs MUNW. LA GLS = left atrial global longitudinal strain, LA SRs = left atrial systolic strain rate, LA SRe = left atrial early-diastolic strain rate, NS = non-significant. Kaplan-Meier curves of adverse events Conclusion Metabolic abnormality may contribute to certain aspects of mechanistic LA dysfunction tightly linked to clinical events, even with normal lean body mass. Our observations may be insightful for targeted interventions in higher-risk patients with subclinical atrial dysfunction.

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