, Volume 57, Issue 1, pp 89–97 | Cite as

Fatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals

  • Yoshitaka Hashimoto
  • Masahide HamaguchiEmail author
  • Takuya Fukuda
  • Akihiro Ohbora
  • Takao Kojima
  • Michiaki Fukui
Original Article



Recent studies identified that metabolically abnormal non-obese phenotype is a risk factor for cardiovascular diseases. However, little is known about risk factor for progression from metabolically healthy non-overweight to metabolically abnormal phenotype. We hypothesized that fatty liver had a clinical impact on progression from metabolically healthy non-overweight to metabolically abnormal phenotype.


In this retrospective cohort study, 14,093 Japanese (7557 men and 6736 women), who received the health-checkup program from 2004 to 2012, were enrolled. Overweight and obesity were defined as body mass index 23.0–25.0 and ≥25.0 kg/m2. Four metabolic factors (impaired fasting glucose, hypertension, hypertriglyceridemia and low high density lipoprotein-cholesterol concentration) were used for definition of metabolically healthy (less than two factors) or metabolically abnormal (two or more). We divided the participants into three groups: metabolically healthy non-overweight (9755 individuals, men/women = 4290/5465), metabolically healthy overweight (2547 individuals, 1800/747) and metabolically healthy obesity (1791 individuals, 1267/524). Fatty liver was diagnosed by ultrasonography.


Over the median follow-up period of 5.3 years, 873 metabolically healthy non-overweight, 512 metabolically healthy overweight and 536 metabolically healthy obesity individuals progressed to metabolically abnormal. The adjusted hazard risks of fatty liver on progression were 1.49 (95% confidence interval 1.20–1.83, p = 0.005) in metabolically healthy non-overweight, 1.37 (1.12–1.66, p = 0.002) in metabolically healthy overweight and 1.38 (1.15–1.66, p < 0.001) in metabolically healthy obesity, after adjusting for age, sex, alcohol, smoking, exercise, impaired fasting glucose, hypertension, hypertriglyceridemia, low high density lipoprotein-cholesterol concentration, and abdominal obesity.


Fatty liver is an independent risk factor for progression from metabolically healthy status to metabolically abnormal phenotype, even in non-overweight individuals.


Non-alcoholic fatty liver disease Metabolic syndrome Insulin resistance Obesity Lean 



We thank all of the staff members in the medical health checkup center at Murakami Memorial Hospital.

Author contributions

Y.H. designed and conducted the study, researched, analyzed and interpreted the data, and wrote the manuscript; M.H. designed and conducted the study, researched and interpreted the data, and reviewed and edited the manuscript. T.F., A.O. and T.K. researched and interpreted the data, and reviewed the manuscript. M.F. designed and conducted the study, researched and interpreted the data, and reviewed the manuscript. All authors have approved the final draft submitted.

Compliance with ethical standards

Conflict of interest

M. Fukui has received grant and research support from AstraZeneca plc, Astellas Pharma Inc., Bristol-Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Kyowa Hakko Kirin Company Ltd., Kowa Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Nippon Chemiphar Company Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Terumo Co. The sponsors were not involved in the study design; in the collection, analysis, interpretation of data; in the writing of this manuscript; or in the decision to submit the article for publication. M. Fukui, his immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article. M. Fukui received no current funding for this study and this does not alter their adherence to all of the journal policies on sharing data and materials. The remaining authors declare that they have no competing interests.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki, and an independent ethics committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismKyoto Prefectural University of Medicine, Graduate School of Medical ScienceKyotoJapan
  2. 2.Department of DiabetologyKameoka Municipal HospitalKyotoJapan
  3. 3.Department of Gastroenterology, Murakami Memorial HospitalAsahi UniversityGifuJapan

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