Relationship of Circulating Fetuin-A Levels with Body Size and Metabolic Phenotypes

Background. Previous studies have suggested the existence of distinct body size subgroups according to metabolic health referred to as metabolically healthy obesity (MHO) and metabolically abnormal but normal weight (MANW) patients. Although nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and metabolic syndrome, the relationship between these phenotypes and fetuin-A, a representative hepatokine, has not been explored. Methods. We examined the association between circulating fetuin-A levels, metabolic health phenotypes, cardiometabolic risk parameters, and subclinical atherosclerosis in 290 subjects who were randomly selected from an ongoing cohort study. Results. Fetuin-A concentrations were significantly associated with detrimental anthropometric and laboratory measurements, including increased waist circumference, blood pressure, alanine aminotransferase, fasting plasma glucose, and triglyceride levels. Furthermore, fetuin-A levels were significantly increased in the metabolically abnormal (MA) group compared to the metabolically healthy (MH) group in subjects without obesity (717.1 [632.1, 769.7] vs. 599.5 [502.0, 709.3], P=0.001) and subjects with obesity (704.1 [595.5-880.9] vs. 612.2 [547.9-802.1], P=0.016). In addition, brachial-ankle pulse wave velocity (baPWV), which reflects arterial stiffness, was higher in MA individuals compared to MH individuals. Multiple logistic regression analysis revealed that both individuals without obesity (P for trend = 0.017) and with obesity (P for trend = 0.028) in the higher tertiles of fetuin-A had an increased risk of MA than those in the lowest tertile. Conclusions. This study demonstrates that fetuin-A levels are significantly associated with metabolic health phenotypes, such as MHO and MANW, in Korean adults.

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Does metabolic health in overweight and obesity persist? – Individual variation and cardiovascular mortality over two decades

Acta Endocrinologica ◽

10.1530/eje-16-0095 ◽

2016 ◽

Vol 175 (2) ◽

pp. 133-143 ◽

Cited By ~ 13

Author(s):

Akaal Kaur ◽

Desmond G Johnston ◽

Ian F Godsland

Keyword(s):

Insulin Resistance ◽

Cardiovascular Risk ◽

Health Status ◽

Cardiovascular Mortality ◽

Normal Weight ◽

Metabolic Health ◽

Overweight And Obesity ◽

Cross Sectional ◽

Increased Risk ◽

Metabolically Healthy

Objective Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. Design Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20years. Methods Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. Results There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95% CI: 1.79–3.65, P<0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08–2.67, P<0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34–3.72, P=0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P=0.007), but proportions converged thereafter. Conclusions Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.

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Metabolically healthy obesity was significantly associated with increased risk of gallstones

Acta Endocrinologica ◽

10.1530/eje-21-0802 ◽

2021 ◽

Author(s):

Sailimai Man ◽

Yongxiang Gao ◽

Jun Lv ◽

Mingkun Tong ◽

Jianchun Yin ◽

...

Keyword(s):

Normal Weight ◽

Metabolic Health ◽

Health Check ◽

Healthy Individuals ◽

Metabolically Healthy Obesity ◽

Increased Risk ◽

History Of ◽

Normal Body Weight ◽

Metabolically Healthy ◽

Cox Proportional Hazard Regression

Objective The risk of gallstones among metabolically healthy obesity (MHO) individuals is largely unexplored. Therefore, the present study investigated the association between MHO and gallstones in a health check-up cohort of Chinese adults. Design A prospective cohort study. Methods Participants included 58,862 individuals from the MJ health check-up cohort aged ≥ 18 years without history of gallstones at baseline. Gallstones were diagnosed using abdominal B-type ultrasound. Metabolically healthy was defined as not having any one of the components of metabolic syndrome. Obesity was identified by body mass index (BMI) and waist circumference (WC). Participants were cross-classified at baseline by metabolic health and obesity. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of gallstones across BMI categories were estimated with Cox proportional hazard regression models. Results During a median follow-up of 3.0 (interquartile range, 1.6-6.1) years, 1,269 participants developed gallstones. Individuals with MHO (HR: 1.95, 95% CI: 1.23, 3.09 for BMI criteria; HR: 1.74, 95% CI: 1.37, 2.21 for WC criteria) had significantly higher risk of gallstones than those with metabolically healthy normal weight. In metabolically healthy individuals, BMI and WC both displayed linear dose-response relationships with gallstones (P for non-linearity > 0.05). The association between MHO and gallstones remained unchanged when using different criteria for metabolic health and obesity. Conclusions MHO was significantly associated with gallstones, suggesting that obesity can independently contribute to gallstones development, even among metabolically healthy individuals. These findings emphasize that metabolically healthy individuals may still benefit from maintaining normal body weight to prevent gallstones.

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Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans

Journal of Diabetes Research ◽

10.1155/2016/4094876 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Shenghui Wu ◽

Susan P. Fisher-Hoch ◽

Belinda Reninger ◽

Kristina Vatcheva ◽

Joseph B. McCormick

Keyword(s):

Mexican Americans ◽

Mexican American ◽

Normal Weight ◽

Metabolic Health ◽

Increased Risk ◽

Mexico Border ◽

Control Of Diabetes ◽

Metabolically Healthy ◽

Obese Phenotype ◽

And Control

Purpose. To compare the risk for diabetes in each of 4 categories of metabolic health and BMI.Methods. Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2. Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication.Results. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype.Conclusions. Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone.

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Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort

International Journal of Stroke ◽

10.1177/1747493016672083 ◽

2016 ◽

Vol 12 (2) ◽

pp. 187-191 ◽

Cited By ~ 17

Author(s):

Laura Sánchez-Iñigo ◽

David Navarro-González ◽

Alejandro Fernández-Montero ◽

Juan Pastrana-Delgado ◽

JA Martínez

Keyword(s):

Ischemic Stroke ◽

Hazard Analysis ◽

Normal Weight ◽

Metabolic Health ◽

Stroke Incidence ◽

Metabolically Healthy Obese ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy

Background Whether obesity is a major risk factor for cardiovascular disease in the absence of metabolic comorbidities remains under debate. Indeed, some obese individuals may be at low risk of metabolic-related complications, while normal-weight individuals may not be “healthy.” Aims To assess the incidence of ischemic stroke according to the metabolic health and obesity states of 5171 participants from the Vascular-Metabolic CUN cohort. Methods A Cox proportional-hazard analysis was conducted to estimate the hazard ratio and their 95% confidence interval of stroke according to the metabolic health and obesity states based on TyG index and Adult Treatment Panel-III criteria, during 9.1 years of follow-up. Results After 50,056.2 person-years of follow-up, 162 subjects developed an ischemic stroke (incidence rate 3.23 per 1000 person-years). Metabolically healthy obese subjects did not show greater risk of stroke, while metabolically unhealthy participants, obese and non-obese, had an increased risk of stroke, compared with healthy non-obese. The hazard ratios for the multivariable adjusted model were 1.55 (95% CI: 1.36–1.77) and 1.86 (95% CI: 1.57–2.21), respectively. Conclusions Metabolically unhealthy individuals exhibited a greater risk of ischemic stroke than metabolically healthy obese individuals.

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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 ◽

Metabolically Healthy Obese ◽

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.

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Systemic Inflammation Characterizes Lack of Metabolic Health in Nonobese HIV-Infected Men

Mediators of Inflammation ◽

10.1155/2018/5327361 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ana N. Monczor ◽

Xiuhong Li ◽

Frank J. Palella ◽

Kristine M. Erlandson ◽

Dorothy Wiley ◽

...

Keyword(s):

Systemic Inflammation ◽

Visceral Fat ◽

Subcutaneous Fat ◽

Normal Weight ◽

Metabolic Health ◽

Model Assessment ◽

Cross Sectional ◽

Inflammatory Biomarker ◽

Hiv Serostatus ◽

Metabolically Healthy

Background. Increasing body mass index (BMI) is generally associated with loss of metabolic health, although some obese individuals remain metabolically healthy. Among nonobese men, HIV infection has been associated with a lower prevalence of metabolic health. Methods. We conducted a cross-sectional analysis of 470 HIV-infected and 368 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study Cardiovascular substudy. Circulating biomarker levels were compared by BMI category and by HIV serostatus. Poisson regression with robust variance determined associations between metabolic health and circulating inflammatory biomarker levels after adjusting for factors previously associated with metabolic health. Results. HIV-infected men were younger and less likely to be obese. Among HIV-infected, normal weight metabolically healthy men (compared to unhealthy) had significantly lower circulating levels of interleukin- (IL-) 6, soluble tumor necrosis factor receptors (sTNFR) I and II, and homeostatic model assessment of insulin resistance (HOMA-IR), higher adiponectin, less visceral fat, and more subcutaneous fat. Among HIV-uninfected normal weight men and obese men (regardless of HIV serostatus), metabolic health was associated only with higher levels of adiponectin, less visceral fat, and lower HOMA-IR values. In multivariate analyses restricted to HIV-infected men, lower hs-CRP, sTNFRI, sTNFRII, and HOMA-IR and higher adiponectin levels were associated with metabolic health. Additional adjustment for visceral adiposity did not alter results. Conclusions. Among HIV-infected normal weight men, metabolic health was associated with less systemic inflammation, a relationship that, among normal weight men, was unique to HIV+ men and did not exist among obese men of either HIV serostatus.

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Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?

Metabolites ◽

10.3390/metabo11110771 ◽

2021 ◽

Vol 11 (11) ◽

pp. 771

Author(s):

Lourdes Balcázar-Hernandez ◽

Lourdes Basurto ◽

Leticia Manuel-Apolinar ◽

Sara Vega-García ◽

Norma Basurto-Acevedo ◽

...

Keyword(s):

Body Size ◽

Cross Sectional Study ◽

Normal Weight ◽

The Body ◽

Metabolic Phenotype ◽

Obese Women ◽

Middle Aged ◽

Cross Sectional ◽

Metabolically Healthy Obese ◽

Metabolically Healthy

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = −0.107; p = 0.047); adiponectin with BMI (r = −0.217; p = 0.001), insulin (r = −0.415; p = 0.0001), HOMA-IR (r = −0.429; p = 0.0001), and VAT (r = −0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF−21 with insulin (r = −0.337; p= 0.030) and HOMA-IR (r = −0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06–1.81)) and a reduction of adiponectin (OR 0.9 (0.84–0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003–1.011)) and MCP-1 (1.044 (1.008–1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.

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Abstract 075: Differences In Body Composition At Baseline And In Response To Exercise Training By Metabolic Health And Weight Status

Circulation ◽

10.1161/circ.143.suppl_1.075 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Alexis Jones ◽

Jacob L Barber ◽

James S Skinner ◽

Claude Bouchard ◽

Mark A Sarzynski

Keyword(s):

Body Composition ◽

Exercise Training ◽

Visceral Fat ◽

Weight Status ◽

Normal Weight ◽

Metabolic Health ◽

Fat Free Mass ◽

Obese Adults ◽

Change Models ◽

Metabolically Healthy

Background: Body composition is known to differ across metabolic health and weight phenotypes. Regular exercise improves body composition, yet little is known about differences in exercise response across metabolic health and weight phenotypes. Methods: Normal weight (n=376) and overweight/obese (OWOB) adults (n=456) from the HERITAGE Family Study (56% female, 38% Black) completed a 20-week endurance training program. Four groups based on baseline BMI and metabolic risk were created: metabolically healthy normal weight, MHNW; metabolically unhealthy normal weight, MUNW; metabolically healthy OWOB, MHO; and metabolically unhealthy OWOB, MUO. Unhealthy was defined as having ≥2 metabolic syndrome components. General linear models tested for differences in baseline and change in measures of body composition (fat mass [FM], fat-free mass [FFM], % body fat [%BF], visceral fat) after adjusting for age, sex, and ethnicity (and baseline value in change models). Results: Table 1 shows adjusted mean baseline and change in body composition values by group. Baseline body composition tended to track with weight status, with NW adults having lower FM, %BF, and visceral fat compared to obese adults (p<0.05), regardless of metabolic health. However, the MHO group had lower baseline values of these traits compared to MUO (p<0.05). Body composition measures significantly improved with exercise training in all groups, however, the magnitude of change differed between groups. For example, both NW groups had larger decreases in %BF compared to the obese groups, with MUNW showing the largest decrease. Conversely, MHNW showed the largest decrease in visceral fat, which was greater than both obese groups, but change in visceral fat was similar between MHO and MUNW. Conclusions: Normal weight adults tended to have better body composition profiles at baseline and larger improvements with exercise compared to obese adults, regardless of metabolic health. Within weight groups, body composition improved regardless of metabolic health status.

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Impact of Transition in Metabolic Health and Obesity on the Incident Chronic Kidney Disease: A Nationwide Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa033 ◽

2020 ◽

Vol 105 (3) ◽

pp. e148-e157 ◽

Cited By ~ 2

Author(s):

Yun Kyung Cho ◽

Jiwoo Lee ◽

Hwi Seung Kim ◽

Joong-Yeol Park ◽

Woo Je Lee ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Confidence Interval ◽

Dynamic Condition ◽

National Sample ◽

Metabolic Health ◽

Hazard Ratio ◽

Longitudinal Change ◽

Increased Risk ◽

Metabolically Healthy

Abstract Context Metabolically healthy obesity (MHO) is a dynamic condition. Objective To evaluate the risk of chronic kidney disease (CKD) among people with MHO according to its longitudinal change. Design Observational study. Setting A nationwide population-based cohort. Participants A total of 514 866 people from the Korean National Health Insurance Service-National Sample Cohort. Intervention The initial presence and changes of obesity (using body mass index [BMI] and waist circumference [WC]) and metabolic health status. Main outcome Measure Incident CKD from 2011 to 2015. Results Of the people classified as MHO at baseline (BMI criteria), 47.6% remained as MHO in 2011 and 2012, whereas 12.1%, 5.5%, and 34.8% were classified as metabolically healthy, non-obese (MHNO), metabolically unhealthy, non-obese, and metabolically unhealthy, obese, respectively. The risk of incident CKD in the baseline MHO group was higher than that in the MHNO group (hazard ratio, 1.23; 95% confidence interval, 1.12-1.36). However, when transition was taken into account, people who converted to MHNO were not at increased risk (hazard ratio, 0.98; 95% confidence interval, 0.72-1.32), whereas the stable MHO group and the groups that evolved to metabolically unhealthy status had a higher risk of incident CKD than the stable MHNO group. When the risk was analyzed using WC criteria, it showed a similar pattern to BMI criteria except for the stable MHO group. Conclusions MHO was a dynamic condition, and people with MHO constituted a heterogeneous group. Although the MHO phenotype was generally associated with incident CKD, maintenance of metabolic health and weight reduction might alleviate the risk of CKD.

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