title: Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease.
abstract: 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.
  
  
  
  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 defined 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.
  
  
  
  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% confidence 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 inflammation status.
  
  
  
  In a large cohort of strictly defined 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.
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Suk
authors.initials: HS
authors.lastname: Jung
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Juhee
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Department of Medicine, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Yun
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Department of Medicine, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazo
authors.affiliation: National Center for Epidemiology, Carlos III Institute of Health and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pastor-Barriuso
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jiin
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chan-Won
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Department of Social and Preventive Medicine, Julius Centre University of Malaya, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rampal
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Ciccarone Center for the Prevention of Heart Disease, Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cainzos-Achirica
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Department of Medicine, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Eun Cheol
authors.initials: EC
authors.lastname: Chung
authors.affiliation: Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hocheol
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.|Department of Medicine, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Ryu
mesh_terms: D000328:Adult; D015992:Body Mass Index; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000000981:diagnostic imaging / Q000453:epidemiology*; D000067329:Obesity, Metabolically Benign / Q000453:epidemiology* / Q000378:metabolism; D050177:Overweight / Q000453:epidemiology / Q000378:metabolism; D016016:Proportional Hazards Models; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology; D012737:Sex Factors; D014463:Ultrasonography