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HOME > Endocrinol Metab > Volume 39(2); 2024 > Article
Letter
Diabetes, obesity and metabolism Multiple Definitions of Fatty Liver Disease: Which One Most Accurately Predicts Diabetes?
Eun-Jung Rheeorcid
Endocrinology and Metabolism 2024;39(2):397-398.
DOI: https://doi.org/10.3803/EnM.2024.202
Published online: April 25, 2024

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Eun-Jung Rhee. Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea Tel: +82-2-2001-2485, Fax: +82-2-2001-1588, E-mail: hongsiri@hanmail.net
• Received: April 4, 2024   • Revised: April 6, 2024   • Accepted: April 10, 2024

Copyright © 2024 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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A few years ago, multinational liver disease academic societies recommended a new definition for fatty liver disease, shifting from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) [1]. The definition of MAFLD is based on the evidence of hepatic steatosis in the presence of at least one of the following three metabolic conditions, overweight/obesity, type 2 diabetes, or the presence of at least two of the metabolic abnormalities. This change was proposed because the term NAFLD does not adequately reflect the pathophysiological causes of fatty liver disease, which are now understood to be insulin resistance and ectopic fat accumulation. Additionally, the label “nonalcoholic” is misleading, as some individuals with NAFLD may consume alcohol in quantities that exceed the threshold defining NAFLD. Last year, an even more precise concept of fatty liver disease was introduced by multinational societies: metabolic dysfunction-associated steatotic liver disease (MASLD) [2]. Again, this new definition was recommended because the term NAFLD fails to encapsulate the pathophysiologic causes and can stigmatize those diagnosed with the disease [3].
According to this new definition, MASLD is defined by the presence of fatty liver disease in conjunction with at least one of five cardiometabolic risk factors, provided that no other cause of fatty liver has been identified. Furthermore, a new category of steatotic liver disease has been introduced: “metabolic dysfunction and alcoholic liver disease (MetALD).” This category applies to individuals who consume alcohol exceeding the threshold for NAFLD but below the threshold for alcoholic liver disease. Experts in the field have emphasized these new definitions because the revisions are grounded in the etiology of the diseases and place a greater emphasis on the pathophysiological mechanisms [3].
NAFLD was previously regarded as a contributing factor to the development of diabetes, with a 2- to 5-fold increased risk for the disease, and diabetes, in turn, influences the progression of NAFLD, reflecting a reciprocal effect on the risk and prognosis of each condition [4,5]. Given that the new definitions of MAFLD and MASLD have evolved from NAFLD, and considering NAFLD’s status as a significant risk factor for type 2 diabetes, it is crucial to analyze the risk and prevention strategies for diabetes in individuals diagnosed with MAFLD or MASLD.
We analyzed the risk of developing diabetes in individuals with MAFLD and MASLD among participants in a health checkup program. The study included 52,606 participants (mean age, 35.4 years) from the Kangbuk Samsung Hospital health checkup program, spanning from 2002 to 2019. These individuals underwent at least 10 health checkups. After applying strict exclusion criteria, 48,147 participants were selected for analysis to monitor the development of diabetes over a median follow-up period of 14.25 years. At the start of the study, 12,289 (25.52%) participants were diagnosed with MAFLD, while 35,801 (74.36%) had MASLD. Throughout the follow-up, 5,815 (12.1%) participants were diagnosed with diabetes mellitus. Among those with MAFLD, 3,067 (25.0%) developed diabetes, compared to 4,806 (13.4%) with MASLD. After adjusting for metabolic risk factors, the hazard ratio for diabetes was 2.57 (95% confidence interval [CI], 1.86 to 3.55) in the MAFLD group, and 2.18 (95% CI, 1.46 to 3.24) in the MASLD group (Table 1). MAFLD was a marginally better predictor of diabetes development than MASLD (Harrell’s C-index: 0.82 [95% CI, 0.79 to 0.85] for MAFLD vs. 0.8 [95% CI, 0.77 to 0.84] for MASLD). Although the difference was not substantial, the findings suggest that both conditions significantly increase the risk of diabetes and are strong predictors of its development.
In conclusion, our preliminary report analyzed data from over 50,000 participants in a health checkup database with a median follow-up of 14.3 years. The results indicate that the two newer definitions of fatty liver disease, MAFLD and MASLD, are associated with more than a 2-fold increased risk for the development of diabetes, which is similar to or slightly higher than that associated with NAFLD. Additionally, both criteria demonstrated strong predictive value for future diabetes development. It will be intriguing to observe the outcomes of numerous studies analyzing the risk of future cardiometabolic diseases and mortality in individuals with MASLD and MetALD, a newly distinguished category of steatotic liver disease.

CONFLICTS OF INTEREST

Eun-Jung Rhee is the deputy editor of the journal. However, she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Table 1.
Risk of Diabetes Development in People with Baseline MAFLD and MASLD within 14.3 Years of Follow-up (n=48,147)
Variable PY Event IR (95% CI)/1,000 PY HR (95% CI)
Crude model Model 1 Model 2 Model 3
MAFLD 653,506.91 5,815 8.9 (8.67–9.13)
 No 497,970.03 2,748 5.52 (5.32–5.73) 1 (reference) 1 (reference) 1 (reference) 1 (reference)
 Yes 155,536.88 3,067 19.72 (19.03–20.43) 3.68 (3.5–3.88) 3.16 (2.99–3.33) 2.68 (2.53–2.83) 2.57 (1.86–3.55)
 Harrell’s C-index 0.68 (0.67–0.68) 0.75 (0.74–0.75) 0.76 (0.75–0.77) 0.82 (0.79–0.85)
MASLD
 No 173,474.31 1,009 5.82 (5.47–6.19) 1 (reference) 1 (reference) 1 (reference) 1 (reference)
 Yes 480,032.6 4,806 10.01 (9.73–10.3) 1.79 (1.67–1.92) 2.54 (2.37–2.73) 2.21 (2.06–2.38) 2.18 (1.46–3.24)
 Harrell’s C-index 0.57 (0.56–0.57) 0.71 (0.7–0.72) 0.74 (0.73–0.75) 0.8 (0.77–0.84)

Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, systolic blood pressure, total cholesterol, and triglycerides; Model 3: adjusted for age, sex, systolic blood pressure, total cholesterol, triglycerides, and homeostatic model assessment for insulin resistance.

MAFLD, metabolic dysfunction-associated fatty liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; PY, person-years; IR, incidence rate; CI, confidence interval; HR, hazard ratio.

  • 1. Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol 2020;73:202–9.PubMed
  • 2. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol 2024;29:101133.PubMed
  • 3. Bae JC. No more NAFLD: the term is now MASLD. Endocrinol Metab (Seoul) 2024;39:92–4.ArticlePubMedPMCPDF
  • 4. Rhee EJ. Nonalcoholic fatty liver disease and diabetes: an epidemiological perspective. Endocrinol Metab (Seoul) 2019;34:226–33.ArticlePubMedPMCPDF
  • 5. Chung SM, Kang MK, Moon JS, Park JG. Performance of simple fibrosis score in non-alcoholic fatty liver disease with and without type 2 diabetes. Endocrinol Metab (Seoul) 2023;38:277–81.ArticlePubMedPMCPDF

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