Metabolically healthy obesity and the development of nonalcoholic fatty liver disease

Yoosoo Chang, Hyun Suk Jung, Juhee Cho, Yiyi Zhang, Kyung Eun Yun, Mariana Lazo-Elizondo, Roberto Pastor-Barriuso, Jiin Ahn, Chan Won Kim, Sanjay Rampal, Miguel Cainzos-Achirica, Di Zhao, Eun Cheol Chung, Hocheol Shin, Eliseo Guallar, Seungho Ryu

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: 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 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. 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% 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. CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)1133-1140
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume111
Issue number8
DOIs
StatePublished - Aug 1 2016

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Incidence
Body Mass Index
Obesity
Metabolically Benign Obesity
Non-alcoholic Fatty Liver Disease
Fatty Liver
Insulin Resistance
Homeostasis
Cohort Studies
Confidence Intervals
Inflammation
Phenotype
Weights and Measures

ASJC Scopus subject areas

  • Medicine(all)
  • Gastroenterology

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Metabolically healthy obesity and the development of nonalcoholic fatty liver disease. / Chang, Yoosoo; Jung, Hyun Suk; Cho, Juhee; Zhang, Yiyi; Yun, Kyung Eun; Lazo-Elizondo, Mariana; Pastor-Barriuso, Roberto; Ahn, Jiin; Kim, Chan Won; Rampal, Sanjay; Cainzos-Achirica, Miguel; Zhao, Di; Chung, Eun Cheol; Shin, Hocheol; Guallar, Eliseo; Ryu, Seungho.

In: American Journal of Gastroenterology, Vol. 111, No. 8, 01.08.2016, p. 1133-1140.

Research output: Contribution to journalArticle

Chang, Y, Jung, HS, Cho, J, Zhang, Y, Yun, KE, Lazo-Elizondo, M, Pastor-Barriuso, R, Ahn, J, Kim, CW, Rampal, S, Cainzos-Achirica, M, Zhao, D, Chung, EC, Shin, H, Guallar, E & Ryu, S 2016, 'Metabolically healthy obesity and the development of nonalcoholic fatty liver disease', American Journal of Gastroenterology, vol. 111, no. 8, pp. 1133-1140. https://doi.org/10.1038/ajg.2016.178
Chang, Yoosoo ; Jung, Hyun Suk ; Cho, Juhee ; Zhang, Yiyi ; Yun, Kyung Eun ; Lazo-Elizondo, Mariana ; Pastor-Barriuso, Roberto ; Ahn, Jiin ; Kim, Chan Won ; Rampal, Sanjay ; Cainzos-Achirica, Miguel ; Zhao, Di ; Chung, Eun Cheol ; Shin, Hocheol ; Guallar, Eliseo ; Ryu, Seungho. / Metabolically healthy obesity and the development of nonalcoholic fatty liver disease. In: American Journal of Gastroenterology. 2016 ; Vol. 111, No. 8. pp. 1133-1140.
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abstract = "OBJECTIVES: 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 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. 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{\%} 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. CONCLUSIONS: 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.",
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AU - Chang, Yoosoo

AU - Jung, Hyun Suk

AU - Cho, Juhee

AU - Zhang, Yiyi

AU - Yun, Kyung Eun

AU - Lazo-Elizondo, Mariana

AU - Pastor-Barriuso, Roberto

AU - Ahn, Jiin

AU - Kim, Chan Won

AU - Rampal, Sanjay

AU - Cainzos-Achirica, Miguel

AU - Zhao, Di

AU - Chung, Eun Cheol

AU - Shin, Hocheol

AU - Guallar, Eliseo

AU - Ryu, Seungho

PY - 2016/8/1

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N2 - OBJECTIVES: 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 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. 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% 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. CONCLUSIONS: 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.

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