Metabolically healthy obesity, transition to unhealthy phenotypes and type 2 diabetes in 0.5 million Chinese adults: The China Kadoorie Biobank

Objectives: To prospectively assess the association of metabolic health status and its transition with incident diabetes risk across body mass index (BMI) categories. Design: Cohort study based on the China Kadoorie Biobank (CKB) Methods: The CKB study enrolled 512,715 adults aged 30-79 years from 10 diverse areas in China during 2004-2008. After exclusion, 432,763 participants were cross-classified by BMI categories and the metabolic status during followed-up for incident diabetes disease. The changes in BMI and metabolic health status were defined from baseline to the second resurvey. Results: Type 2 diabetes risk is higher for metabolically healthy obese (MHO) subjects than metabolically healthy normal weight (MHN) individuals (HR: 3.97, 95% CI: 3.64-3.66), and it is highest for those affected by metabolically healthy obese (MUO) (HR: 6.47, 95% CI: 6.17-6.79). About 15.26% of participants with MHN converted to metabolically healthy overweight or obesity (MHOO), whereas 48.40% of MHOO remained unconverted throughout the follow-up. In obese or overweight people, the conversion from metabolically healthy to unhealthy might increase the chances of developing diabetes as compared to those with a stable metabolic healthy state (HR: 3.70, 95% CI: 2.99-4.59), while those with persistent metabolic disorders are most likely to have diabetes (HR: 8.32, 95% CI: 7.08-9.78). Conclusions: Metabolic healthy is a transient state, and individuals converted from metabolically healthy status to unhealthy phenotypes across all BMI categories might raise the risk of diabetes.

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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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Metabolically Healthy Obesity—Heterogeneity in Definitions and Unconventional Factors

Metabolites ◽

10.3390/metabo10020048 ◽

2020 ◽

Vol 10 (2) ◽

pp. 48 ◽

Cited By ~ 5

Author(s):

Inês Brandão ◽

Maria João Martins ◽

Rosário Monteiro

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Normal Weight ◽

Metabolic Dysfunction ◽

Metabolically Healthy Obese ◽

Healthy Obese ◽

Metabolically Healthy ◽

Contaminant Accumulation ◽

Metabolic Endotoxemia

The concept of heterogeneity among obese individuals in their risk for developing metabolic dysfunction and associated complications has been recognized for decades. At the origin of the heterogeneity idea is the acknowledgement that individuals with central obesity are more prone to developing type 2 diabetes and cardiovascular disease than those with peripheral obesity. There have been attempts to categorize subjects according to their metabolic health and degree of obesity giving rise to different obese and non-obese phenotypes that include metabolically unhealthy normal-weight (MUHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Individuals belonging to the MHO phenotype are obese according to their body mass index although exhibiting fewer or none metabolic anomalies such as type 2 diabetes, dyslipidemia, hypertension, and/or unfavorable inflammatory and fribinolytic profiles. However, some authors claim that MHO is only transient in nature. Additionally, the phenotype categorization is controversial as it lacks standardized definitions possibly blurring the distinction between obesity phenotypes and confounding the associations with health outcomes. To add to the discussion, the factors underlying the origin or protection from metabolic deterioration and cardiometabolic risk for these subclasses are being intensely investigated and several hypotheses have been put forward. In the present review, we compare the different definitions of obesity phenotypes and present several possible factors underlying them (adipose tissue distribution and cellularity, contaminant accumulation on the adipose tissue, dysbiosis and metabolic endotoxemia imposing on to the endocannabinoid tone and inflammasome, and nutrient intake and dietary patterns) having inflammatory activation at the center.

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Abstract 17843: Visceral Adipose Tissue Secretion of Adiponectin Decreases with Increased Body Mass Index

Circulation ◽

10.1161/circ.130.suppl_2.17843 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Lenore R Rengel ◽

Brittaney Obi ◽

Jon Gould ◽

Matthew Goldblatt ◽

Andrew Kastenmeier ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Metabolic Health ◽

Metabolically Healthy Obese ◽

Obese Subjects ◽

Healthy Obese ◽

Metabolically Healthy ◽

Visceral Adipose ◽

Subcutaneous Adipose

Introduction: Peripheral adiposity is associated with better metabolic health and higher plasma adiponectin (ADPN) levels. Since ADPN is secreted mainly by adipose tissue (AT), it is intriguing that higher visceral adipose tissue (VAT) is associated with lower ADPN levels and poor metabolic health. Hypothesis: We hypothesized that various AT depots differ in their ability to secrete ADPN. Methods: Paired AT samples (VAT and subcutaneous adipose tissue (SAT)) were collected from 19 subjects (10 women, 15 obese) undergoing elective abdominal surgery. The samples were cultured and the supernatant was collected after 24 hours. ADPN levels released into the supernatant from VAT and SAT were measured using multiplex methods. Subjects were defined as obese or non-obese (NO) based on BMI > or ≤ 30kg/m2 respectively. Obese subjects were further classified as metabolically unhealthy obese (MUO) or metabolically healthy obese (MHO) based on presence or absence of type 2 diabetes mellitus, hypertension, or cardiovascular disease at the time of surgery. Results: Mean ADPN secretion levels from SAT and VAT were similar in NO subjects (17.3 ± 3.4 vs. 9.8 ± 13.0 ng/mL/mg, p=0.5) whereas the mean ADPN secretion was lower from VAT among obese subjects (15.9 ± 0.8 vs. 4.5 ± 0.2 ng/mL/mg, p=0.0002). ADPN secretion decreased from VAT (r=-0.16) and increased from SAT (r=0.33) with increased BMI (Fig.1). When MHO and MUO were compared, ADPN secretion from VAT in MHO was reduced only slightly (16.1 ± 8.2 vs. 4.0 ± 2.0 ng/mL/mg, p=0.07) whereas ADPN secretion was significantly reduced in MUO (15.9 ± 5.3 vs. 4.7 ± 4.6 ng/mL/mg, p=0.003). Conclusions: Reduced ADPN secretion from VAT in subjects with increasing BMI may explain lower circulating ADPN levels in obese individuals. Higher ADPN production from SAT and the relatively preserved secretion of ADPN from VAT may explain metabolic health in some obese individuals. Futures studies will help identify factors that control ADPN secretion from AT.

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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 ◽

Metabolically Healthy Obese ◽

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.

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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 ◽

Metabolically Healthy Obese ◽

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

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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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