Metabolically healthy obesity: Is it really benign?

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity

Recently, a subgroup of patients with obesity but without cardiometabolic abnormalities has attracted considerable attention and has been characterized as metabolically healthy obese (MHO) patients. MHO is quite prevalent among patients with obesity. Even though these subjects have less pronounced metabolic abnormalities compared with patients with metabolically unhealthy obesity (MUO), they are at increased risk for progressing to MUO and for developing cardiovascular disease. Accordingly, diet, exercise and appropriate pharmacotherapy should be recommended to patients with MHO as strongly as in those with MUO.

Metabolically healthy obesity and the risk of all-cause and cardiovascular disease mortality in a Korean population: a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2021-049063 ◽

2021 ◽

Vol 11 (9) ◽

pp. e049063

Author(s):

Seong-Ah Kim ◽

Kyungjoon Lim ◽

Jong-Koo Lee ◽

Daehee Kang ◽

Sangah Shin

Keyword(s):

Cardiovascular Disease ◽

Elevated Risk ◽

Korean Population ◽

All Cause Mortality ◽

Healthy Obese ◽

Metabolically Healthy ◽

Reduced Risk ◽

Cvd Mortality

ObjectivesThis study aimed to examine the association between metabolically healthy obesity and all-cause and cardiovascular disease (CVD) mortality in a Korean population.DesignA prospective study.SettingThis study used data from the Korean Genome and Epidemiology Study.ParticipantsA total of 140 137 participants were followed up over a median period of 9.2 years. Participants were categorised into four groups according to obesity (obese: body mass index ≥25 kg/m2 or non-obese) and metabolic health (metabolically unhealthy: two or more metabolic abnormalities or metabolically healthy).Primary and secondary outcome measuresAll-cause and CVD mortality of the participants until 31 December 2018 were ascertained by the National Health Insurance Service of beneficiary status of Korea.ResultsMetabolically unhealthy non-obese participants were at elevated risk of all-cause mortality (HR, 1.12; 95% CI, 1.04 to 1.21; p=0.0019) and CVD mortality (HR, 1.39; 95% CI, 1.17 to 1.65; p=0.0002), particularly mortality from ischaemic heart disease (IHD) (HR, 1.54; 95% CI, 1.10 to 2.14; p=0.0116) compared with metabolically healthy non-obese participants. Surprisingly, metabolically healthy obese participants were at reduced risk of all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.98; p=0.0197). Metabolically unhealthy obese participants were at elevated risk of CVD mortality (HR, 1.51; 95% CI, 1.26 to 1.81; p<0.0001) and IHD mortality (HR, 1.88; 95% CI, 1.35 to 2.63; p=0.0002) compared with metabolically healthy non-obese participants.ConclusionsIn a Korean population, metabolically healthy obese participants had reduced risk of all-cause mortality compared with their non-obese counterparts, whereas metabolically unhealthy participants had elevated risk of CVD mortality, in particular mortality from IHD regardless of obesity.

Abstract 13508: Obesity Phenotype and the Risk of Hypertension and Type 2 Diabetes: Does Cardiorespiratory Fitness Matter?

Circulation ◽

10.1161/circ.130.suppl_2.13508 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sae Young Jae ◽

Mercedes Carnethon ◽

Won Hah Park ◽

Bo Fernhall

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Cardiorespiratory Fitness ◽

Normal Weight ◽

Incident Hypertension ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy

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.

Diabetes and Cardiovascular Disease Outcomes in the Metabolically Healthy Obese Phenotype: A cohort study

Diabetes Care ◽

10.2337/dc12-1971 ◽

2013 ◽

Vol 36 (8) ◽

pp. 2388-2394 ◽

Cited By ~ 250

Author(s):

S. L. Appleton ◽

C. J. Seaborn ◽

R. Visvanathan ◽

C. L. Hill ◽

T. K. Gill ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Disease Outcomes ◽

Healthy Obese ◽

Metabolically Healthy ◽

Obese Phenotype

The Risk of Incident Type 2 Diabetes in a Korean Metabolically Healthy Obese Population: The Role of Systemic Inflammation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3885 ◽

2015 ◽

Vol 100 (3) ◽

pp. 934-941 ◽

Cited By ~ 42

Author(s):

Chang Hee Jung ◽

Min Jung Lee ◽

Yu Mi Kang ◽

Jung Eun Jang ◽

Jaechan Leem ◽

...

Keyword(s):

Type 2 Diabetes ◽

Systemic Inflammation ◽

Incident Type ◽

Increased Risk ◽

Incident Type 2 Diabetes ◽

Healthy Obese ◽

Metabolically Healthy ◽

Inflammation Group

Abstract Objective: This study sought to investigate whether the metabolically healthy obese (MHO) phenotype is associated with an increased risk of incident type 2 diabetes in a Korean population and, if so, whether systemic inflammation affects this risk in MHO individuals. Design and Methods: The study population comprised 36 135 Koreans without type 2 diabetes. Participants were stratified by body mass index (cutoff value, 25.0 kg/m2) and metabolic health state (assessed using Adult Treatment Panel-III criteria). High-sensitive C-reactive protein (hsCRP) was used as a surrogate marker of systemic inflammation. Subjects were classified into low (ie, hsCRP < 0.5 mg/L) and high (ie, hsCRP ≥ 0.5 mg/L) systemic inflammation groups. Results: During a median followup of 36.5 months (range, 4.8–81.7 mo), 635 of the 36 135 individuals (1.8%) developed type 2 diabetes. The MHO group had a significantly higher risk of incident type 2 diabetes (multivariate-adjusted hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.16–2.11) than the metabolically healthy nonobese (MHNO) group. However, the risk of the MHO group varied according to the degree of systemic inflammation. Compared with the MHNO/low systemic inflammation group, the risk of type 2 diabetes in the MHO/low systemic inflammation group was not significantly elevated (multivariate-adjusted HR, 1.61; 95% CI, 0.77–3.34). However, the MHO/high systemic inflammation group had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 3.73; 95% CI 2.36–5.88). Conclusions: MHO subjects show a substantially higher risk of incident type 2 diabetes than MHNO subjects. The level of systemic inflammation partially explains this increased risk.

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 ◽

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.

Abstract P230: Metabolically Healthy Obesity and QT interval. The Polish Norwegian Study

Circulation ◽

10.1161/circ.135.suppl_1.p230 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Georgeta Vaidean ◽

Marta Manczuk ◽

Jared W Magnani

Keyword(s):

Qt Interval ◽

Large Population ◽

Ventricular Repolarization ◽

Qtc Interval ◽

Benign Condition ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy ◽

Age And Sex

Introduction: Obesity has been linked to increased risk of sudden cardiac death and ventricular arrhythmia. Whether the metabolically healthy obese phenotype is a benign condition, is debatable and few studies examined its ventricular repolarization profile. Purpose: To examine the association of metabolically healthy/unhealthy obesity phenotypes with prolonged corrected QT (QTc) interval in a large population-based study. Methods: Cross-sectional data from an ongoing cohort study in Poland. Data was collected using a standardized protocol. The QT intervals were obtained from digital standard 12-lead resting ECG and were corrected for heart rate by Bazett’s formula. Plasma lipids and glucose were measured in a fasting state. After excluding drugs known to affect the QT interval (antiarrhythmics, digoxin, antipsychotics), the analytic sample size was 11068 participants, ages 45 to 64 years. Based on the presence of obesity (BMI ge 30 kg/ m 2 ) and metabolic syndrome (per the AHA/NHLBI harmonized definition), we defined four phenotypes: metabolically healthy non-obese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Multivariable linear and logistic regression models were used for analyses. Results: The prevalence of the 4 phenotypes was: MHNO: 51.34%, MUNO: 18.07%, MHO: 10.07%, MUO: 20.52%. The prevalence of an increased QTc interval (greater than >430ms in men/450ms in women) was 14.28%, and the prevalence of a highly prolonged QTc interval (greater than 450ms in men/470ms in women) was 5.2%. The age- and sex-adjusted mean QTc across the 4 phenotypes was: MHNO: 417.05ms (416.39- 417.71; MUNO: 418.82 ms (417.71-419.92); MHO: 420.46 ms (418.99 -421.93); MUO: 422.45 ms (421.41-423.49). The age- and sex adjusted odds (OR, 95% CI) of an increased QTc interval (greater than 430/450ms in men/women) were increased in MUNO (1.11, 0.96-1.29), MHO (1.44, 1.20-1.72) and MUO (1.47, 1.28-1.69), compared to MHNO phenotype. These estimates were minimally attenuated after additional adjustment for prevalent CVD, LVH on ECG, smoking, alcohol intake, physical activity and education: MUNO (1.10, 0.94-1.28), MHO (1.45, 1.21-1.73) and MUO (1.44, 1.26-1.66). We did not detect effect modification by sex. We obtained similar results in subgroup analyses restricted to those without diabetes and after excluding those with third degree atrioventricular blocks or conduction abnormalities with QRS>120ms. Conclusion: Both metabolically healthy- and non-healthy obese phenotypes had a higher likelihood of an increased/borderline QTc interval compared to the MHNO phenotype. Our study furthered our understanding of ventricular repolarization as reflected in the QTc interval, in the setting of different obesity phenotypes.

Risk of Arterial Stiffness According to Metabolically Healthy Obese Phenotype: A Combined Cross-Sectional and Longitudinal Study in Kailuan Cohort

10.21203/rs.3.rs-97966/v1 ◽

2020 ◽

Author(s):

Anxin Wang ◽

Yu Wang ◽

Yingting Zuo ◽

Xue Tian ◽

Shuohua Chen ◽

...

Keyword(s):

Longitudinal Study ◽

Health Status ◽

Arterial Stiffness ◽

Metabolic Health ◽

Cross Sectional ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy ◽

Healthy Participants

Abstract BackgroundTo investigate the risk of incident arterial stiffness according to metabolically healthy obese (MHO) phenotype in Chinese population.Materials and methodsThe Kailuan study is an ongoing prospective cohort study, 37,180 participants with at least one-time measurement of branchial-ankle pulse wave velocity (baPWV) were included in the cross-sectional analysis, and 16,236 participants with repeated measurement of baPWV during the follow-ups were included in the longitudinal study from March 1, 2010, to January 31, 2020. Cross-classification of body mass index (BMI) categories and metabolic health status created six groups. Linear and logistic regression analyses were used to assess the association between BMI-metabolic status phenotypes and baPWV in mono-factor and multi-factor models. ResultsThe results of cross-sectional and longitudinal investigation were basically the same, as the abnormality of baPWV increased with BMI categories in metabolically healthy participants, while the increasing tendency disappeared in metabolically unhealthy participants. A 1.6-fold, 2.8-fold increased risk for the new occurrence of arterial stiffness were documented in MHO and metabolically unhealthy obese participants compared to metabolically healthy normal weight controls in the fully adjusted model. Further stratified analysis shown that metabolic health status was an interaction factor between BMI and arterial stiffness in either study population (P<0.0001 for cross-sectional study and P=0.0003 for longitudinal study).ConclusionsMetabolic health status and BMI categories contribute to the progression of arterial stiffness, while BMI is positively associated with arterial stiffness only in metabolically healthy participants. Moreover, MHO is an intermediate stage between metabolically healthy and unhealthy status.Trial registration: ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050

Apolipoproteins A-I, B, and C-III and Obesity in Young Adult Cherokee

Journal of Lipids ◽

10.1155/2017/8236325 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Wenyu Wang ◽

Piers Blackett ◽

Sohail Khan ◽

Elisa Lee

Keyword(s):

Young Adult ◽

Logistic Regression Model ◽

Height Ratio ◽

Related Risk ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy ◽

Atherogenic Lipid ◽

Waist Height Ratio

Since young adult Cherokee are at increased risk for both diabetes and cardiovascular disease, we assessed association of apolipoproteins (A-I, B, and C-III in non-HDL and HDL) with obesity and related risk factors. Obese participants (BMI ≥ 30) aged 20–40 years (n=476) were studied. Metabolically healthy obese (MHO) individuals were defined as not having any of four components of the ATP-III metabolic syndrome after exclusion of waist circumference, and obese participants not being MHO were defined as metabolically abnormal obese (MAO). Associations were evaluated by correlation and regression modeling. Obesity measures, blood pressure, insulin resistance, lipids, and apolipoproteins were significantly different between groups except for total cholesterol, LDL-C, and HDL-apoC-III. Apolipoproteins were not correlated with obesity measures with the exception of apoA-I with waist and the waist : height ratio. In a logistic regression model apoA-I and the apoB : apoA-I ratio were significantly selected for identifying those being MHO, and the result (C-statistic = 0.902) indicated that apoA-I and the apoB : apoA-I ratio can be used to identify a subgroup of obese individuals with a significantly less atherogenic lipid and apolipoprotein profile, particularly in obese Cherokee men in whom MHO is more likely.

Association of Metabolically Healthy and Unhealthy Obesity Phenotype with Markers Related to Obesity, Diabetes among Young, Healthy Adult Men. Analysis of MAGNETIC Study

Life ◽

10.3390/life11121350 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1350

Author(s):

Mateusz Lejawa ◽

Kamila Osadnik ◽

Zenon Czuba ◽

Tadeusz Osadnik ◽

Natalia Pawlas

Keyword(s):

Plasminogen Activator Inhibitor ◽

Normal Weight ◽

Obese Patients ◽

Plasminogen Activator Inhibitor 1 ◽

Metabolic Markers ◽

Adult Men ◽

Metabolically Healthy ◽

Metabolically Unhealthy Obesity

Adipose tissue secretes many regulatory factors called adipokines. Adipokines affect the metabolism of lipids and carbohydrates. They also influence the regulation of the immune system and inflammation. The current study aimed to evaluate the association between markers related to obesity, diabesity and adipokines and metabolically healthy and unhealthy obesity in young men. The study included 98 healthy participants. We divided participants into three subgroups based on body mass index and metabolic health definition: 49 metabolically healthy normal-weight patients, 27 metabolically healthy obese patients and 22 metabolically unhealthy obese patients. The 14 metabolic markers selected were measured in serum or plasma. The analysis showed associations between markers related to obesity, diabesity and adipokines in metabolically healthy and unhealthy obese participants. The decreased level of adipsin (p < 0.05) was only associated with metabolically healthy obesity, not with metabolically unhealthy obesity. The decreased level of ghrelin (p < 0.001) and increased level of plasminogen activator inhibitor-1 (p < 0.01) were only associated with metabolically unhealthy obesity, not with metabolically healthy obesity. The decreased level of adiponectin and increased levels of leptin, c-peptide, insulin and angiopoietin-like 3 protein were associated with metabolically healthy and unhealthy obesity. In conclusion, our data show that metabolically healthy obesity was more similar to metabolically unhealthy obesity in terms of the analyzed markers related to obesity and diabesity.

Metabolically Healthy Obesity and Physical Fitness in Military Males in the CHIEF Study

10.21203/rs.3.rs-119378/v1 ◽

2020 ◽

Author(s):

Sheng-Huei Wang ◽

Pei-Shou Chung ◽

Yen-Po Lin ◽

Kun-Zhe Tsai ◽

Ssu-Chin Lin ◽

...

Keyword(s):

Alcohol Intake ◽

Analysis Of Covariance ◽

Physically Active ◽

P Values ◽

Male Cohort ◽

Healthy Obese ◽

Metabolically Healthy ◽

The Difference

Abstract The metabolically healthy obese (MHO) characterized by the absence of abdominal obesity have been reported to have superior cardiorespiratory fitness (CRF) than the metabolically unhealthy obese (MUO). However, this finding might be biased by the baseline sedentary behavior in the general population.This study utilized 3,669 physically active military males aged 18-50 years in Taiwan. Obesity and metabolically unhealthy were respectively defined as body mass index ≥27.5 kg/m2 and waist circumference ≥90 cm, specifically for Asian male adults. Four groups were accordingly classified as the metabolically healthy lean (MHL, n=2,607), metabolically unhealthy lean (MUL, n=234), MHO (n=208) and MUO (n=620). CRF was evaluated by time for a 3-kilometer run, and muscular strengths were separately assessed by numbers of push-up and sit-up within 2 minutes. Analysis of covariance was utilized to compare the difference in each exercise performance between groups adjusting for age, service specialty, smoking, alcohol intake, and physical activity.The prevalence of metabolic syndrome in MUO, MHO, MUL and MHL was 45.3% 13.0%, 29.1% and 3.7%, respectively. The performance of CRF did not differ between MHO and MUO (895.3±5.1 sec and 891.5±3.1 sec, p=0.68) which were both inferior to MUL and MHL (877.5±4.8 sec and 849.5±1.4 sec, all p-values <0.05). The performance of muscular strengths evaluated by 2-minute push-ups did not differ between MUL and MUO (44.8±0.2 and 45.2±0.5, p=0.40) which were both less than MHO and MHL (48.1±0.8 and 50.5±0.2, all p-values <0.05). However, the performance of 2-minute sit- ups were only superior in MHL (48.0±0.2) as compared with MUL, MHO and MUO (46.0±0.5, 46.7±0.5 and 46.2±0.3, respectively, all p-values <0.05).Our findings suggested that in a physically active male cohort, the MHO might have greater muscle strengths, but have similar CRF level compared with the MUO.