Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis

Sung, Ki‐Chul; Cha, Sung-Chul; Sung, Joo-Wook; So, Min-Suk; Byrne, Christopher D.

doi:10.1016/j.numecd.2013.07.005

Cited by 57 publications

(65 citation statements)

References 29 publications

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“…LIVER VOLUME 111 | AUGUST 2016 on the risk of NAFLD has rarely been reported in previous studies. A previous cross-sectional study showed a higher prevalence of fatty liver among MHO individuals, but this study did not consider other risk factors for fatty liver such as excessive alcohol consumption, or compare obese with non-obese participants (including overweight and underweight participants in the reference group) ( 16 ). Furthermore, the cross-sectional design resulted in temporal ambiguity of exposure and outcome.…”

Section: Discussionmentioning

confidence: 96%

“…Th e health implications of MHO are controversial (13)(14)(15). Only one study has evaluated the association of MHO with NAFLD ( 16 ). In this study, MHO subjects had an increased prevalence of NAFLD compared with metabolically healthy non-obese subjects, but the cross-sectional design of this study limited its ability to establish a temporal relation between obesity and NAFLD.…”

Section: Introductionmentioning

confidence: 90%

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Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

Chang

Jung

Cho

et al. 2016

American Journal of Gastroenterology

182

153

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The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women. METHODS:A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defi ned as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound. RESULTS:During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confi dence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women ( P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low infl ammation status. CONCLUSIONS:In a large cohort of strictly defi ned metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se , regardless of metabolic abnormalities, can increase the risk of NAFLD. Am J Gastroenterol 2016; 111:1133-1140 doi: 10.1038/ajg.2016 Specifi cally, it is unclear whether obesity is a risk factor for NALFD in subjects who do not have any of the metabolic abnormalities associated with excess adiposity, a group oft en described as metabolically healthy obese (MHO) ( 11,12 ). Th e health implications of . Only one study has evaluated the association of MHO with NAFLD ( 16 ). In this study, MHO subjects had an increased prevalence of NAFLD compared with metabolically healthy non-obese subjects, but the cross-sectional design of this study limited its ability to establish a temporal relation between obesity and NAFLD.No cohort study has evaluated the role of MHO as a determinant of incident NAFLD among subjects free of NAFLD at baseline. Th erefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women who participated in a health screening examination program. METHODS Study populationTh e Kangbuk Samsung Health Study is a cohort study of men and women 18 years of age or older who underwent a comprehensive annual or biennial health examination at the clinics of the Kangbuk Samsu...

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 90%

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

Chang

Jung

Cho

et al. 2016

American Journal of Gastroenterology

182

153

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“…Previously, one study examined the cross-sectional association between obesity and NAFLD using data from a large Korean occupational cohort, and showed that the prevalence of ultrasonography-diagnosed NAFLD amongst 945 individuals with MHO was 45% 8 . Using data from the same occupational cohort, Chang et al have now developed the work further and have undertaken a retrospective cohort study to examine relationships between BMI categories and incident NAFLD, having excluded patients who were metabolically abnormal at baseline (defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance of less than 2.5) 1 .…”

Section: Standfirst (51 Words)mentioning

confidence: 99%

Metabolically healthy obesity and NAFLD

Targher

Byrne

2016

Nat Rev Gastroenterol Hepatol

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Refers to Standfirst (51 words)Obesity is a risk factor for several noncommunicable diseases, but some individuals with obesity remain metabolically healthy throughout life; whether these individuals are at risk of developing NAFLD is uncertain. In a new study, Chang et al. showed a statistically significant, graded relationship between BMI and NAFLD in metabolically healthy individuals.Obesity is known to be an important risk factor for a whole range of noncommunicable diseases that include type 2 diabetes mellitus (T2DM), chronic obstructive sleep apnoea, various types of cancers (e.g., colorectal cancer, oesophagus and breast cancer after the menopause) and NAFLD. Although the fact that obesity increases risk of certain diseases is well accepted by clinicians, evidence has shown that some individuals who are obese are also metabolically healthy: so-called metabolically healthy obesity (MHO).In a recent retrospective cohort study involving metabolically healthy individuals, Chang et al. found that BMI categories are positively associated with an increased incidence of NAFLD, suggesting that the obese phenotype, regardless of metabolic abnormalities, might increase the risk of developing NAFLD 1 .Increasing evidence suggests that BMI, the most common proxy measure used to help categorize overweight or obesity, is an imprecise measure of body-fat-related risk of noncommunicable diseases. Rather, other features associated with overweight or obesity, such as visceral fat mass, adipose tissue inflammation, adipose tissue function, or factors such as insulin resistance and metabolic syndrome components, might be the key pathogenetic aspects that mediate increased risk of noncommunicable diseases in individuals with overweight or obesity (TABLE 1). Nevertheless, the concept of MHO has gained much interest in the scientific community.MHO is a complex, emerging phenotype with risks intermediate between metabolically healthy individuals with normal-weight and individuals who are metabolically abnormal with obesity (MAO). Compared with metabolically healthy individuals with normal-weight, persons with obesity are at increased risk of all-cause and cause-specific mortality and cardiovascular disease events even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight 2-4 . However, compared with their peers who are MAO, individuals with MHO have lower risk of all-cause and cause-specific mortality 2-4 . Furthermore, studies suggest that individuals with MHO have similar insulin sensitivity to lean individuals, as well as lower liver fat content and lower intimal-medial thickness of the carotid artery compared with individuals who are MAO 5,6 . Agreement on a universally accepted definition of MHO, however, would improve the design of future studies and would facilitate comparisons between studies.Obesity is a much stronger risk factor for T2DM than for cardiovascular disease, suggesting that there could be differential effects of fat mass, fat function or other obesity-rel...

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“…Healthy obese women have also shown more subcutaneous fat in the thigh than unhealthy obese women (31), likely reflecting a genderbiased pattern of fat storage. Others have gone further, demonstrating lower traces of fat in the liver among healthy than among unhealthy obese adults ( [34][35][36], which is strongly deterministic of insulin resistance (25). A recent experimental study demonstrated that adults who were initially unhealthy obese were more likely than those initially healthy obese to gain fat in visceral stores in response to an equal amount of diet-induced weight gain over a period of 2 weeks (37).…”

Section: What Explains Healthy Obesity?mentioning

confidence: 99%

“…'Healthy' is a matter of binary labelling based on clinical cut-points, and subtle differences in these metabolic risk factors may exist between obese and normal-weight adults who are both given this label, which would reveal important differences in subclinical disease burden. Studies which have examined differences in continuous levels of metabolic risk factors between healthy obese and healthy normal-weight adults report that blood lipids, blood pressure, and insulin resistance are indeed more adverse among the healthy obese (20,36,54,55). Levels of coronary artery calcification have also been found to be higher among healthy obese than among healthy normal-weight adults (56), providing more direct evidence of subclinical cardiovascular disease burden; calcification was not higher in one additional study (36) but this lack of difference may be due to reliance on a restrictive sub-sample of healthy obese adults who were free of hypertension and type 2 diabetes, given that differences in calcification were mediated by such factors in the larger study (56).…”

Section: Is Healthy Obesity Harmless?mentioning

confidence: 99%

Healthy obesity as an intermediate state of risk: a critical review

Bell

Hamer

2016

Expert Review of Endocrinology & Metabolism

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Introduction: Obesity is a top public health priority but interventions to reverse the condition have had limited success. About 1-in-3 obese adults are free of metabolic risk factor clustering and are considered 'healthy', and much attention has focused on the implications of this state for obesity management. Areas covered:We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal-weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary:Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease.

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Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis

Cited by 57 publications

References 29 publications

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

Metabolically healthy obesity and NAFLD

Healthy obesity as an intermediate state of risk: a critical review

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