Endocrinology and Metabolism

Original Articles

Fibrate-Statin Combination Therapy and Change of Hepatic Steatosis-Related Indices in Patients with Dyslipidemia: A Retrospective Study Using Korean National Health Insurance Data: Jong Han Choi, Bongseong Kim, Kyungdo Han, Dong-Lim Kim, Suk Kyeong Kim, Keeho Song; Received January 6, 2026 Accepted March 25, 2026 Published online July 7, 2026; DOI: https://doi.org/10.3803/EnM.2026.2891 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The role of fibrates in modifying hepatic steatosis-related outcomes remains uncertain, particularly in real-world populations receiving statin therapy for dyslipidemia. We investigated the association between fibrate use and longitudinal changes in hepatic steatosis-related indices in statin-treated patients with moderate hypertriglyceridemia using nationwide health screening data.
Methods
We analyzed data from 307,992 adults with triglyceride level of 150–500 mg/dL receiving statin therapy, identified from the Korean National Health Insurance Service database. Participants were classified according to fibrate exposure (users vs. non-users). Hepatic steatosis was operationally assessed using two validated surrogate indices, the fatty liver index (FLI) and the hepatic steatosis index (HSI), measured at baseline and follow-up health checkups. Propensity score matching was performed to balance baseline characteristics. Subgroup analyses were conducted according to medication possession ratio (MPR <0.8 vs. ≥0.8).
Results
In propensity score-matched analyses, fibrate use was associated with lower odds of hepatic steatosis as defined by FLI (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95) and HSI (OR, 0.82; 95% CI, 0.78 to 0.87). Among participants with high medication adherence (MPR ≥0.8), stronger associations were observed (FLI OR, 0.30; HSI OR, 0.34).
Conclusion
In this large nationwide cohort, fibrate use in statin-treated patients with moderate hypertriglyceridemia was associated with lower prevalence of hepatic steatosis-related indices, particularly among individuals with high medication adherence. These findings should be interpreted as associations based on surrogate markers rather than definitive evidence of histologic improvement. Further studies incorporating imaging or histological endpoints are warranted to clarify the role of fibrates in the management of metabolic dysfunction-associated steatotic liver disease.

Impact of Fatty Liver Index on Cardiovascular Disease and Mortality across Alcohol Consumption Levels in Young Adults: Byung-Hun Han, Joonyub Lee, Hun-Sung Kim, Jae-Hyoung Cho, Kyungdo Han, Seung-Hwan Lee; Received October 13, 2025 Accepted January 22, 2026 Published online March 30, 2026; DOI: https://doi.org/10.3803/EnM.2025.2710 [Epub ahead of print]

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Background
The fatty liver index (FLI) is widely used as a surrogate marker for metabolic dysfunction-associated steatotic liver disease, but its predictive value among individuals who consume alcohol remains uncertain. We aimed to investigate the association between FLI and the risk of cardiovascular disease (CVD) and mortality in young adults by alcohol consumption status.
Methods
Using the Korean National Health Information Database, we identified 6,487,686 individuals aged 20–39 years who underwent health examinations between 2009 and 2012. FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase, and categorized as <30, 30–59, or ≥60. Alcohol consumption was classified as non-drinking, mild, moderate, or heavy using sex-specific thresholds. Risks of CVD—including myocardial infarction (MI) and stroke—and all-cause mortality were evaluated using multivariable Cox proportional hazards models.
Results
During a mean follow-up of 13.3 years, 49,399 MI, 29,842 stroke, and 53,330 deaths were identified. The risk of CVD and mortality increased stepwise across higher FLI categories in all alcohol consumption groups. Compared with participants with FLI <30, the adjusted hazard ratios (95% confidence intervals [CIs]) for composite outcome among those with FLI ≥60 were 1.72 (95% CI, 1.67 to 1.77) in non-drinkers, 1.41 (95% CI, 1.38 to 1.43) in mild drinkers, 1.19 (95% CI, 1.15 to 1.24) in moderate drinkers, and 1.20 (95% CI, 1.12 to 1.30) in heavy drinkers. The association was strongest among non-drinkers (P for interaction <0.0001).
Conclusion
FLI is a useful and practical indicator for predicting CVD and mortality in young adults, regardless of alcohol intake, with the highest predictive performance in non-drinkers.

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Association Between Metabolic Obesity Phenotypes and Alcohol-Associated Fatty Liver Disease Among US Adults: A NHANES 2013–2018 Analysis
Priyanka Dadha, Fatima Sayyed, Shakeel Ahmed, Alok Dwivedi, Jennifer Molokwu
Journal of Clinical Medicine.2026; 15(14): 5726. CrossRef

Trends in Prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Nationwide Survey in Korea: Junhyun Kwon, Hanbit Shin, Dae Ho Lee, Eunji Kim; Received July 24, 2025 Accepted October 15, 2025 Published online December 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2578 [Epub ahead of print]

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Background
The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD), which is associated with higher risks of obesity, type 2 diabetes mellitus, cardiovascular disease, chronic kidney disease, and extrahepatic cancer, is increasing. This study aimed to examine the temporal trends in MASLD prevalence among Korean adults, with a focus on age-stratified patterns and related health conditions.
Methods
This secondary analysis of Korea National Health and Nutrition Examination Survey data included data of 90,912 adults aged ≥19 years from 2007 to 2023. MASLD was defined as having the presence of at least one cardiometabolic risk factor and no heavy alcohol consumption. Temporal trends in MASLD prevalence and associated cardiometabolic risk factors were examined across age groups using weighted prevalence estimates and log-linear regression models.
Results
The overall prevalence of MASLD increased from 25.0% in 2007–2009 to 31.0% in 2022–2023 (annual percent change [APC], 1.36%). The most substantial increase was observed in young adults aged 19–44 years (22.3% to 30.5%; APC=2.09%), particularly among men. Middle-aged (45–64 years) and older (≥65 years) adults showed relatively stable or modest increases over time. Among young adults with MASLD, chronic kidney disease prevalence increased from 2.1% to 5.7%.
Conclusion
This nationwide study revealed a significant and continuous increase in MASLD prevalence among Korean adults, particularly in younger age groups. The disproportionate burden in these populations, along with high rates of metabolic comorbidities, underscores an emerging public health concern that may place considerable strain on future healthcare systems.

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Impact of probiotics and prebiotics on glucose/lipid metabolism in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications
Yinan Zhao, Ziyan Li, Guoying Yu
Frontiers in Nutrition.2026;[Epub] CrossRef

Diabetes, obesity and metabolism
Fatty Liver Index Dynamics as a Predictor of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus and Non-Cirrhotic Livers: Eun-Hee Cho, Min Gu Kang, Chang Hun Lee, Shinyoung Oh, Chen Shen, Ha Ram Oh, Young Ran Park, Hyun Lee, Jong Seung Kim, Ji Hyun Park; Endocrinol Metab. 2025;40(6):883-892. Published online May 29, 2025; DOI: https://doi.org/10.3803/EnM.2024.2286

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Background
Type 2 diabetes mellitus (T2DM) is a significant risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease; however, surveillance strategies for patients with T2DM, especially without cirrhosis, are inadequate. This study examined whether the fatty liver index (FLI) and its dynamic changes can effectively identify patients with T2DM at increased risk for HCC.
Methods
Data from 92,761 individuals with T2DM aged 40 to 79 who underwent two health screenings (2012 to 2015) were analyzed. The FLI, calculated using waist circumference, body mass index, triglycerides, and gamma-glutamyl transferase, was used to stratify patients by baseline FLI and FLI changes between screenings. HCC cases were identified via International Classification of Diseases codes and reimbursement records (2016 to 2020).
Results
Patients with baseline FLI of 30 to 59.9 had a 1.90-fold higher risk (P<0.01) and those with FLI ≥60 had a 2.94-fold higher risk (P<0.01) of developing HCC compared to those with FLI <30. An increase in FLI from <30 to ≥30 resulted in a 2.10-fold higher risk of HCC (P<0.01), while a reduction in FLI from ≥30 to <30 led to a 0.64-fold lower risk (P=0.03). Protective benefits of FLI reduction took approximately 3 years to manifest.
Conclusion
Baseline and dynamic monitoring of FLI effectively identified HCC risk in T2DM patients with non-cirrhotic livers, supporting early detection and intervention.

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Risk Assessment and Prediction of Hepatocellular Carcinoma in Noncirrhotic Metabolic Dysfunction-Associated Steatotic Liver Disease
Emilie K. Mitten, Piero Portincasa, György Baffy
International Journal of Molecular Sciences.2026; 27(7): 3241. CrossRef
Impact of Fatty Liver Index on Cardiovascular Disease and Mortality across Alcohol Consumption Levels in Young Adults
Byung-Hun Han, Joonyub Lee, Hun-Sung Kim, Jae-Hyoung Cho, Kyungdo Han, Seung-Hwan Lee
Endocrinology and Metabolism.2026;[Epub] CrossRef
Circulating GDF15 levels reflect metabolic and inflammatory burden in early dysglycemia: findings from the ADIOS cohort
Ji Yoon Kim, Ah Hyeon Lee, Jiyoon Lee, Hye-Min Jang, Sin Gon Kim, Dong-Hoon Kim, Nam Hoon Kim
Diabetes Research and Clinical Practice.2026; 239: 113461. CrossRef

Diabetes, obesity and metabolism
Sodium-Glucose Cotransporter-2 Inhibitor Enhances Hepatic Gluconeogenesis and Reduces Lipid Accumulation via AMPK-SIRT1 Activation and Autophagy Induction: Si Woo Lee, Hyunki Park, Minyoung Lee, Hyangkyu Lee, Eun Seok Kang; Endocrinol Metab. 2025;40(4):583-597. Published online May 12, 2025; DOI: https://doi.org/10.3803/EnM.2024.2223

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Background
Sodium-glucose cotransporter type 2 (SGLT2) inhibitors, such as dapagliflozin, are primarily used to lower glucose in type 2 diabetes. Recent studies suggest broader metabolic effects, particularly in the liver. This study explores the molecular mechanisms by which dapagliflozin influences hepatic glucose and lipid metabolism, hypothesizing that it activates the 5’-adenosine monophosphate-activated protein kinase (AMPK)-sirtuin 1 (Sirt1) pathway to promote gluconeogenesis and reduce lipid accumulation via autophagy.
Methods
HepG2 hepatocellular carcinoma cells were treated with dapagliflozin, and Western blotting, quantitative reverse transcription polymerase chain reaction, and fluorescence microscopy were used to assess gluconeogenic enzyme expression and autophagy. In vivo, mice with liver-specific autophagy related 7 (Atg7) deletion and those on a high-fat diet were used to evaluate glucose regulation, lipid metabolism, and autophagy.
Results
Dapagliflozin significantly increased expression of gluconeogenic enzymes like phosphoenolpyruvate carboxykinase (PEPCK) in HepG2 cells and enhanced autophagic flux, evidenced by increased light chain 3B (LC3B)-II levels and autophagosome formation. AMPK-Sirt1 activation was confirmed as the underlying mechanism. Additionally, dapagliflozin reduced fatty acid synthesis by suppressing enzymes such as acetyl-CoA carboxylase and fatty acid synthase, while promoting fatty acid degradation via carnitine palmitoyltransferase 1α (CPT1α) upregulation. In high-fat diet mice, dapagliflozin increased hepatic gluconeogenesis and reduced lipid accumulation, though serum cholesterol and triglyceride levels were unaffected.
Conclusion
Dapagliflozin enhances hepatic gluconeogenesis and reduces steatosis by activating the AMPK-Sirt1 pathway and promoting autophagy. These findings suggest that SGLT2 inhibitors could offer therapeutic benefits for managing hepatic lipid disorders, beyond glycemic control.

Citations

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The Emerging Therapeutic Promise of SGLT2 Inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease
Wenjing Zhang, Huaidong Hu
Digestive Diseases and Sciences.2026; 71(3): 852. CrossRef
Association of SGLT2 inhibitors use with a lower risk of biliary diseases in patients with type 2 diabetes mellitus: a retrospective cohort study
Ming Gao, Qiuyu Lin, Kaiyue Hu, Bei Zhong, Tingyi Zhu, Zheng Gong, Kaini Zhang, Xiaoli Chen, Xinyu Chen, Ying Zhang, Yangyang Li, Shaowen Tang, Dongming Su, Xiubin Liang, Yu Liu
Annals of Medicine.2026;[Epub] CrossRef
Redefining SGLT2 inhibitors through cytoprotective mechanisms
Sanja Stankovic, Zoran Miloradovic, Vladimir Petrovic, Milan Stoiljkovic
European Journal of Pharmacology.2026; 1016: 178647. CrossRef
Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options
Ruizhe Ren, Xiao Liang, Xiyang Wei
Molecular Biomedicine.2026;[Epub] CrossRef
Mechanism of swertiamarin and novel nitrogen-containing metabolites (R)-Gentiandiol and (S)-Gentiandiol in treating non-alcoholic fatty liver disease in rats: an untargeted metabolomics study based on UPLC-Q-TOF/MS
Yidan Sun, Fuyan Cui, Shuhan Tang, Pengyu Li, Yaqi Xu, Hao Li, Yige Wang, Xintong Li, Minyue Zhang, Rong Ma, Xianna Li, Hongying Xu, Ying Wang, Hailong Zhang, Zhigang Wang
Frontiers in Pharmacology.2025;[Epub] CrossRef
SGLT2 Inhibitors as Systemic Metabolic Modulators: Linking Glucose Excretion to Liver Function Restoration
Seung Wan Noh, Han Sol Ryu, Yong-Ho Kim, Byung-Chul Oh
Endocrinology and Metabolism.2025; 40(6): 851. CrossRef

Brief Reports

Diabetes, obesity and metabolism
Characteristics of Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Risk for Hepatic Fibrosis in 476,124 Korean Adults: A Cross-Sectional Study: Da Yeon Lee, Ji-Hee Ko, Han-Na Jang, Sun Joon Moon, Hye-Mi Kwon, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Eun-Jung Rhee; Endocrinol Metab. 2025;40(4):648-652. Published online March 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2281

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As the new terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) has emerged, the clinical significance of MASLD is increasing. This cross-sectional study analyzed 476,124 health checkup participants (2002–2022) to compare hepatic fibrosis risks across MASLD, MetALD, non-alcoholic fatty liver disease (NAFLD), and metabolic dysfunction-associated fatty liver disease (MAFLD). Steatotic liver was identified via ultrasonography, and fibrosis risk was assessed using aspartate aminotransferase to platelet ratio index and NAFLD fibrosis score. The prevalence of NAFLD, MAFLD, MASLD, and MetALD was 30.1%, 32.3%, 29.8%, and 3.0%, respectively, with a 27.9% overlap among three conditions. Participants with steatotic liver were predominantly male, with higher glucose, lipids, liver enzymes, and homeostasis model assessment of insulin resistance levels. Three disease definitions largely overlapped, with MASLD and NAFLD being very similar, while participants with MAFLD and MetALD showed increased fibrosis risk (clinical trial registration number: 2024-11-050).

Citations

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Associations between steatotic liver disease subtypes and incident diabetes in young Korean adults: A nationwide cohort study
Goh Eun Chung, Su Jong Yu, Jeayeon Park, Yoon Jun Kim, Jung‐Hwan Yoon, Kyungdo Han, Eun Ju Cho
Diabetes, Obesity and Metabolism.2026; 28(3): 1947. CrossRef
Epidemiology and characteristics of obesity in Koreans based on the 2024 Obesity Fact Sheet
Eun-Jung Rhee
Journal of the Korean Medical Association.2026; 69(1): 4. CrossRef
Using an integrative multi-omics and in vitro approach to investigate the role of tris(2-butoxyethyl) phosphate in promoting hepatic steatosis
Gang Zhou, Xihan Gu, Xinyao Zhou, Shuai Chen, Hanyang Liu, Jing Wang
BMJ Open Gastroenterology.2026; 13(1): e002123. CrossRef
Distinct Laboratory and Clinical Features of Metabolic and Alcohol-Related Liver Disease (MetALD): A Systematic Review and Meta-Analysis
Maria Tampaki, Vasileios Lekakis, Christos Chologkitas, Stergios Α. Polyzos, Evangelos Cholongitas
Current Obesity Reports.2026;[Epub] CrossRef
Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef

Diabetes, obesity and metabolism
Association of Steatotic Liver Disease with Retinal Vascular Occlusion: The Influence of Obesity in a Large Health Screening Cohort: Younjin Oh, Su Jeong Song; Endocrinol Metab. 2025;40(2):299-303. Published online February 12, 2025; DOI: https://doi.org/10.3803/EnM.2024.2181

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In this cross-sectional study, we aimed to investigate the relationship between steatotic liver disease (SLD) and retinal abnormalities in a cohort undergoing health screening. Our study included 353,607 participants who underwent fundus photography and abdominal ultrasonography at least once at the Kangbuk Samsung Health Promotion Center from 2002 to 2022. After adjusting for age and sex, the risk of retinal vein occlusion (RVO) significantly increased with the presence of non-alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, and metabolic dysfunction-associated SLD, with odds ratios of 1.259 (95% confidence interval [CI], 1.050 to 1.510), 1.498 (95% CI, 1.249 to 1.796), and 1.342 (95% CI, 1.121 to 1.605), respectively. However, these associations weakened after adjusting for body mass index. No statistically significant associations were observed with other retinal disorders after adjusting for age, sex, and other confounding factors. Our findings suggest that obesity may mediate the relationship between SLD and RVO, while other retinal abnormalities may be more closely associated with known risk factors rather than SLD itself.

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Association Between Baseline Smoking Exposure and Incident Branch Retinal Vein Occlusion: A Retrospective Cohort Study
EunAh Kim, Nak Gyeong Ko, Mihyeon Jin
Ophthalmic Epidemiology.2026; : 1. CrossRef

Original Articles

Thyroid
Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean: Hye In Kim, Jun Young Kim, Jung Hwan Cho, Ji Min Han, Sunghwan Suh, Ji Cheol Bae, Tae Hyuk Kim, Sun Wook Kim, Jong Ryeal Hahm, Jae Hoon Chung; Endocrinol Metab. 2025;40(1):135-145. Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040

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Background
The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.
Methods
This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.
Results
During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.
Conclusion
In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

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Association Between Thyroid Dysfunction and Non-Alcoholic Fatty Liver Disease: A Systematic Review
Tanya ., Aryan Kler, Sunil Singh Bains
International Journal of Health Sciences and Research.2025; : 171. CrossRef

Diabetes, obesity and metabolism
Protective Effects of Melatonin in High-Fat Diet-Induced Hepatic Steatosis via Decreased Intestinal Lipid Absorption and Hepatic Cholesterol Synthesis: Hyungjune Ku, Yeonji Kim, Alvin Lyle Kim, Garam Lee, Youngsik Choi, Bukyung Kim; Endocrinol Metab. 2023;38(5):557-567. Published online September 1, 2023; DOI: https://doi.org/10.3803/EnM.2023.1672

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Background
The preventative effect of melatonin on the development of obesity and the progression of fatty liver under a high-fat diet (HFD) has been well elucidated through previous studies. We investigated the mechanism behind this effect regarding cholesterol biosynthesis and regulation of cholesterol levels.
Methods
Mice were divided into three groups: normal chow diet (NCD); HFD; and HFD and melatonin administration group (HFD+M). We assessed the serum lipid profile, mRNA expression levels of proteins involved in cholesterol synthesis and reabsorption in the liver and nutrient transporters in the intestines, and cytokine levels. Additionally, an in vitro experiment using HepG2 cells was performed.
Results
Expression of hepatic sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) demonstrated that melatonin administration significantly reduces hepatic cholesterol synthesis in mice fed an HFD. Expression of intestinal sodium-glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), GLUT5, and Niemann-pick C1-like 1 (NPC1L1) demonstrated that melatonin administration significantly reduces intestinal carbohydrate and lipid absorption in mice fed an HFD. There were no differences in local and circulatory inflammatory cytokine levels among the NCD, HFD, and HFD+M group. HepG2 cells stimulated with palmitate showed reduced levels of SREBP, LDLR, and HMGCR indicating these results are due to the direct mechanistic effect of melatonin on hepatocytes.
Conclusion
Collectively, these data indicate the mechanism behind the protective effects of melatonin from weight gain and liver steatosis under HFD is through a reduction in intestinal caloric absorption and hepatic cholesterol synthesis highlighting its potential in the treatment of obesity and fatty liver disease.

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Sleep Deprivation Exacerbates High‐Fat Diet‐Induced Obesity and MAFLD Through Melatonin Reduction Mediated NF‐κB Activation
Renjiao Liu, Yiping Zhou, Chongyang Wei, Xincheng Wang, Huiyu Hao, Lifeng Wang, Yakun Ma, Yi Wang, Chunjun Li, Dongyan Chen
Journal of Pineal Research.2026;[Epub] CrossRef
Lipid metabolism-MAFLD crosstalk: mechanisms and therapy
Bojia Li, Shengai Piao, Yin Fu, Qiang Fu, Peiyao Qin, Weitai Kong, Yidi Ma, Zhe Zhang, Xue Fang, Xiaoyang Hu
Frontiers in Endocrinology.2026;[Epub] CrossRef
Melatonin Prevents the Progression of MASLD via Inhibiting FFAs-Induced Ferroptosis through KEAP1/NRF2/HO-1 Pathway
Shuojiao Li, Peng Rao, Wenxian Yu, Yue Tang, Xuanpeng Jiang, Jiatao Liu
Biomolecules & Therapeutics.2025; 33(5): 876. CrossRef
Effect of melatonin on adipokines, biochemical parameters, clock genes, and lipid metabolism in a rat obesity model
Héctor Edmundo Álvarez-Loredo, Esther Layseca-Espinosa, Claudia Inés Victoria-Campos, Héctor Hernández-Mendoza, Estefanía Chávez-Prieto, María Judith Rios-Lugo
Hormones.2025; 24(4): 1067. CrossRef
Melatonin in the pathogenesis and treatment of metabolic liver diseases
Karen B. Ovanesov, Natalia V. Bakulina
Reviews on Clinical Pharmacology and Drug Therapy.2025; 23(4): 337. CrossRef
Influence of dark deprivation on the ultrastructure and mitochondrial apparatus of rat hepatocytes
David A. Areshidze
Morphology.2024; 161(3): 53. CrossRef

Diabetes, obesity and metabolism
Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study: Ji Min Han, Jung Hwan Cho, Hye In Kim, Sunghwan Suh, Yu-Ji Lee, Jung Won Lee, Kwang Min Kim, Ji Cheol Bae; Endocrinol Metab. 2023;38(4):418-425. Published online July 12, 2023; DOI: https://doi.org/10.3803/EnM.2023.1729

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Background
Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes.
Methods
We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41–57 HU), and moderate to severe hepatic steatosis (≤40 HU).
Results
During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63).
Conclusion
We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

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Metabolic Dysfunction-Associated Steatotic Liver Disease: The Role of Hepatic Steatosis in Insulin Resistance and Metabolic Health
Ji Cheol Bae
Endocrinology and Metabolism.2025; 40(2): 304. CrossRef
Diagnostic accuracy of convolutional neural networks in classifying hepatic steatosis from B-mode ultrasound images: a systematic review with meta-analysis and novel validation in a community setting in Telangana, India
Akshay Jagadeesh, Chanchanok Aramrat, Santosh Rai, Fathima Hana Maqsood, Adarsh Kibballi Madhukeshwar, Santhi Bhogadi, Judith Lieber, Hemant Mahajan, Santosh Kumar Banjara, Alexandra Lewin, Sanjay Kinra, Poppy Mallinson
The Lancet Regional Health - Southeast Asia.2025; 40: 100644. CrossRef
Opportunistic AI-derived adiposity measures from coronary artery calcium scans predict new-onset type 2 diabetes in adults without obesity or hyperglycemia: insights from the AI-CVD study within MESA
Morteza Naghavi, Amir Azimi, Kyle Atlas, Anthony P. Reeves, Chenyu Zhang, Jakob Wasserthal, Seyed Reza Mirjalili, Mohammadhossein Mozafarybazargany, Ali Hashemi, Thomas Atlas, Claudia I. Henschke, David F. Yankelevitz, Jeffrey I. Mechanick, Andrea D. Bran
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef

Brief Report

Diabetes, obesity and metabolism
Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes: Seung Min Chung, Min Kyu Kang, Jun Sung Moon, Jung Gil Park; Endocrinol Metab. 2023;38(2):277-281. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1635

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This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

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Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction–associated steatotic liver disease
Xiaolong Qi, Jie Li, Cyrielle Caussy, Gao-Jun Teng, Rohit Loomba
Hepatology.2026; 83(3): 661. CrossRef
Hepatorenal vulnerability flagged by glomerular hyperfiltration in metabolic liver disease: a large health-screening cohort evidence
Dae-Jeong Koo, Yun Tae Kim, Sun-Joon Moon, Hyemi Kwon, Se Eun Park, Sang Min Lee, Cheol-Young Park, Won-Young Lee, Sung Rae Cho, Eun-Jung Rhee
Diabetology & Metabolic Syndrome.2026;[Epub] CrossRef
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Original Article

Diabetes, Obesity and Metabolism
The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018: Ji Cheol Bae, Lauren A. Beste, Kristina M. Utzschneider; Endocrinol Metab. 2022;37(3):455-465. Published online June 21, 2022; DOI: https://doi.org/10.3803/EnM.2022.1434

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Background
We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods
We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results
Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion
Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

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Review Article

Diabetes, Obesity and Metabolism
State-of-the-Art Overview of the Pharmacological Treatment of Non-Alcoholic Steatohepatitis: Yongin Cho, Yong-ho Lee; Endocrinol Metab. 2022;37(1):38-52. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.102

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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the current treatment for NAFLD/NASH is limited to lifestyle modifications, and no drugs are currently officially approved as treatments for NASH. Many global pharmaceutical companies are pursuing the development of medications for the treatment of NASH, and results from phase 2 and 3 clinical trials have been published in recent years. Here, we review data from these recent clinical trials and reports on the efficacy of newly developed antidiabetic drugs in NASH treatment.

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Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
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Original Articles

Diabetes, Obesity and Metabolism
Dulaglutide Ameliorates Palmitic Acid-Induced Hepatic Steatosis by Activating FAM3A Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2022;37(1):74-83. Published online February 9, 2022; DOI: https://doi.org/10.3803/EnM.2021.1293

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Background
Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA).
Methods
HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting.
Results
Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation.
Conclusion
These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.

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Arya Singh, Rahnuma Ahmad, Kona Chowdhury, Mahendra Narwaria, Mainul Haque
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Sukwoo Han, Jaehee Shin, Jae Cheon Kim, Dong Hee Na
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Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes
Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-DeMarzio
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Jinmi Lee, Eun-Jung Rhee, Yu-Mi Lim, Seok-Woo Hong, Won-Young Lee
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Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan
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Inha Jung, Dae-Jeong Koo, Won-Young Lee
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Salvatore Corrao, Chiara Pollicino, Dalila Maggio, Alessandra Torres, Christiano Argano
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Fan Chen, Tingting Hao, Qiang Chen, Yuning Sun, Yanan Shen, Zengqi Zhao, Jianlong Du, Yueru Li, Kangsen Mai, Qinghui Ai
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Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE^−/−FXR^−/− Mice: Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi; Endocrinol Metab. 2021;36(6):1243-1253. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1100

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Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)^−/− and ApoE^−/−FXR^−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE^−/− mice, ApoE^−/−FXR^−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE^−/−FXR^−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

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Review Article

Diabetes, Obesity and Metabolism
Serotonergic Regulation of Hepatic Energy Metabolism: Jiwon Park, Wooju Jeong, Chahyeon Yun, Hail Kim, Chang-Myung Oh; Endocrinol Metab. 2021;36(6):1151-1160. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1331

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The liver is a vital organ that regulates systemic energy metabolism and many physiological functions. Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease and end-stage liver failure. NAFLD is primarily caused by metabolic disruption of lipid and glucose homeostasis. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic amine with several functions in both the central and peripheral systems. 5-HT functions as a neurotransmitter in the brain and a hormone in peripheral tissues to regulate systemic energy homeostasis. Several recent studies have proposed various roles of 5-HT in hepatic metabolism and inflammation using tissue-specific knockout mice and 5-HT-receptor agonists/antagonists. This review compiles the most recent research on the relationship between 5-HT and hepatic metabolism, and the role of 5-HT signaling as a potential therapeutic target in NAFLD.

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Original Articles

Diabetes, Obesity and Metabolism
The Leg Fat to Total Fat Ratio Is Associated with Lower Risks of Non-Alcoholic Fatty Liver Disease and Less Severe Hepatic Fibrosis: Results from Nationwide Surveys (KNHANES 2008–2011): Hyun Min Kim, Yong-ho Lee; Endocrinol Metab. 2021;36(6):1232-1242. Published online November 23, 2021; DOI: https://doi.org/10.3803/EnM.2021.1087

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Background
The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea.
Methods
This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used.
Results
The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis.
Conclusion
A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

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Heterogeneous associations of regional adipose depots with liver fibrosis in U.S. adults
Kuan-Yu Lai, Chun-Yi Wang, Hsian-Han Kao, Wen-Yuan Lin, Tsung-Po Chen
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Low leg fat mass is associated with low insulin sensitivity, inflammatory markers, and β-cell dysfunction in non-obese Japanese people
Satomi Minato-Inokawa, Mari Honda, Ayaka Tsuboi-Kaji, Mika Takeuchi, Kaori Kitaoka, Miki Kurata, Bin Wu, Tsutomu Kazumi, Keisuke Fukuo
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Body composition mediates the association between fatty acids and NAFLD risk: a prospective cohort study
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Waistline to thigh circumference ratio as a predictor of MAFLD: a health care worker study with 2-year follow-up
Xiaoyan Hao, Honghai He, Liyuan Tao, Wei Zhao, Peng Wang
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Regional fat distribution and hepatic fibrosis and steatosis severity in patients with nonalcoholic fatty liver disease and type 2 diabetes
Asieh Mansour, Saeed Pourhassan, Hadis Gerami, Mohammad Reza Mohajeri‐Tehrani, Marziye Salahshour, Ali Abbasi, Elham Madreseh, Sayed Mahmoud Sajjadi‐Jazi
Obesity Science & Practice.2024;[Epub] CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Adipose tissue insulin resistance index was inversely associated with gluteofemoral fat and skeletal muscle mass in Japanese women
Satomi Minato-Inokawa, Mari Honda, Ayaka Tsuboi-Kaji, Mika Takeuchi, Kaori Kitaoka, Miki Kurata, Bin Wu, Tsutomu Kazumi, Keisuke Fukuo
Scientific Reports.2024;[Epub] CrossRef
A greater ratio of thigh subcutaneous fat to abdominal fat is associated with protection against non-alcoholic fatty liver disease
Yebei Liang, Peizhu Chen, Siyu Chen, Dan Liu, Fusong Jiang, Zhijun Zhu, Keqing Dong, Li Wei, Xuhong Hou
JHEP Reports.2023; 5(7): 100730. CrossRef
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Dae Eon Kang, Si Nae Oh
Nutrients.2023; 15(18): 3901. CrossRef

Diabetes, Obesity and Metabolism
Changes in Insulin Resistance Index and the Risk of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease without Diabetes: Kangbuk Samsung Health Study: Dae-Jeong Koo, Mi Yeon Lee, Inha Jung, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(5):1016-1028. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1110

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Background
Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.
Methods
We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (<0), G2 (0–0.50), G3 (0.51–1.00), and G4 (>1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).
Results
After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m². The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4).
Conclusion
Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

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Minjeong Sung, Dae-Hwan Kim, Eun-Gene Sun, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung, Hyun-Jeong Shim, Woo Kyun Bae
Endocrinology and Metabolism.2026; 41(1): 121. CrossRef
Insulin Resistance as a Dynamic Correlate of Fibrosis Status in Chronic Hepatitis B: A Visit-Level Longitudinal Risk Stratification Framework
Abdalwahab Omar Alshammari, Idris Adewale Ahmed
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Insulin Resistance and Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients Under Antiviral Therapy
Dong Hyun Sinn, Kyung-Ah Kim, Jung Il Lee, Geum-Youn Gwak
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Metabolic Dysfunction-Associated Steatotic Liver Disease: The Role of Hepatic Steatosis in Insulin Resistance and Metabolic Health
Ji Cheol Bae
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Associations between non-insulin-based insulin resistance surrogate markers and liver-related outcomes in metabolic dysfunction-associated steatotic liver disease: a nationwide cohort study in South Korea
Sang Yi Moon, Minkook Son, Yeo Wool Kang, Myeongseok Koh, Jong Yoon Lee, Yang Hyun Baek
BMC Gastroenterology.2025;[Epub] CrossRef
Application of insulin resistance score in type 2 diabetes mellitus complicated with fatty liver and liver fibrosis
Shaojie Duan, Mengdie Chen, Jie Chen, Yaojian Shao, Xiaolong Jin, Chaohui Wang, Ping Feng, Xiaosheng Teng, Zhenjun Yu
European Journal of Gastroenterology & Hepatology.2025; 37(10): 1155. CrossRef
Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis
Mohammad E. Khamseh, Mojtaba Malek, Soodeh Jahangiri, Sohrab Nobarani, Azita Hekmatdoost, Marieh Salavatizadeh, Samira Soltanieh, Haleh Chehrehgosha, Hoda Taheri, Zeinab Montazeri, Fereshteh Attaran, Faramarz Ismail-Beigi, Fariba Alaei-Shahmiri
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Gyuri Kim, Tae Yang Yu, Jae Hwan Jee, Ji Cheol Bae, Mira Kang, Jae Hyeon Kim
Diabetes & Metabolism.2024; 50(3): 101534. CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Effects of luseogliflozin on suspected MASLD in patients with diabetes: a pooled meta-analysis of phase III clinical trials
Takumi Kawaguchi, Kenta Murotani, Hiromitsu Kajiyama, Hitoshi Obara, Hironori Yamaguchi, Yuko Toyofuku, Fumi Kaneko, Yutaka Seino, Saeko Uchida
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O. Kozak
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Yu Luo, Cuiyu Wang, Tian Zhang, Xiaoyu He, Jianan Hao, Andong Shen, Hang Zhao, Shuchun Chen, Luping Ren
International Journal of General Medicine.2023; Volume 16: 293. CrossRef
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Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
Nutrients.2022; 14(14): 2795. CrossRef
Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
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Diabetes, Obesity and Metabolism
Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability: Inha Jung, Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2021;36(4):845-854. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1098

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Background
Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.
Methods
We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.
Results
On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).
Conclusion
Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

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Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
Nature Reviews Gastroenterology & Hepatology.2022; 19(10): 638. CrossRef
Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
Nutrients.2022; 14(14): 2795. CrossRef
Higher Weight Variability Could Bring You a Fatty Liver
Yeoree Yang, Jae-Hyoung Cho
Endocrinology and Metabolism.2021; 36(4): 766. CrossRef
Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease
Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
Frontiers in Endocrinology.2021;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts: Jiwon Kim, Minyoung Lee, Soo Yeon Kim, Ji-Hye Kim, Ji Sun Nam, Sung Wan Chun, Se Eun Park, Kwang Joon Kim, Yong-ho Lee, Joo Young Nam, Eun Seok Kang; Endocrinol Metab. 2021;36(4):823-834. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1074

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Background
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM.
Methods
A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD.
Results
Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters.
Conclusion
The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinical practice.

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An interpretable machine learning model for predicting metabolic dysfunction‐associated steatotic liver disease in patients with type 2 diabetes
Zhuolin Zhou, Nan Gao, Jiaojiao Liu, Xuerong Ma, Zhijuan Ge, Cheng Ji
Diabetes, Obesity and Metabolism.2026; 28(1): 122. CrossRef
Surveying the features of screening strategies for non-alcoholic fatty liver disease: A scoping review
Nazanin Mir, Hamid R Baradaran, Seidamir Pasha Tabaeian, Nasrin Abolhasanbeigi Gallehzan, Aziz Rezapour
Journal of Education and Health Promotion.2026;[Epub] CrossRef
Prevalence, Sonographic Characteristics, and Metabolic Predictors of Nonalcoholic Fatty Liver Disease in Adults With Type 2 Diabetes in Tanzania
Zubeir Zubeir, Zuhura Nkrumbih, Salama Ally, Yasser H. Hadi
Dr. Sulaiman Al Habib Medical Journal.2025; 7(3): 180. CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma
Marcin Kosmalski, Agnieszka Śliwińska, Józef Drzewoski
Biomedicines.2023; 11(4): 1097. CrossRef

Diabetes, Obesity and Metabolism
High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study: Sung-Woo Kim, Jae-Han Jeon, Jun Sung Moon, Mi Kyung Kim; Endocrinol Metab. 2021;36(4):800-809. Published online August 20, 2021; DOI: https://doi.org/10.3803/EnM.2021.1040

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Background
Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.
Methods
This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Results
The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.
Conclusion
Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

Citations

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The clinical features and outcomes of diabetes patients infected with COVID-19: a systematic review and meta-analysis comprising 192,693 patients
Kai Liu, Shu Liu, Ting-ting Xu, Hong Qiao
Frontiers in Medicine.2025;[Epub] CrossRef
Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy
Raffaele Galiero, Giuseppe Loffredo, Vittorio Simeon, Alfredo Caturano, Erica Vetrano, Giulia Medicamento, Maria Alfano, Domenico Beccia, Chiara Brin, Sara Colantuoni, Jessica Di Salvo, Raffaella Epifani, Riccardo Nevola, Raffaele Marfella, Celestino Sard
PLOS ONE.2024; 19(5): e0296495. CrossRef
COVID-19 and hepatic injury: Diversity and risk assessment
Fares E M Ali, Mostafa K Abd El-Aziz, Mahmoud M Ali, Osama M Ghogar, Adel G Bakr
World Journal of Gastroenterology.2023; 29(3): 425. CrossRef
Differential Effects of COVID-19 Hospitalization on the Trajectory of Liver Disease Progression
Dilara Hatipoğlu, Connor Mulligan, Jeffrey Wang, Juan Peticco, Reid Grinspoon, Sanjay Gadi, Camilla Mills, Jay Luther, Raymond T. Chung
Gastro Hep Advances.2023; 2(4): 480. CrossRef
Association of non-alcoholic fatty liver and metabolic-associated fatty liver with COVID-19 outcomes: A systematic review and meta-analysis
Gowthami Sai Kogilathota Jagirdhar, Rakhtan K Qasba, Harsha Pattnaik, Kaanthi Rama, Akshat Banga, Shiva Teja Reddy, Anna Carolina Flumignan Bucharles, Rahul Kashyap, Praveen Reddy Elmati, Vikas Bansal, Yatinder Bains, Theodore DaCosta, Salim Surani
World Journal of Gastroenterology.2023; 29(21): 3362. CrossRef
COVID-19 and Fatty Liver Disorders
Maria Guarino, Valentina Cossiga, Francesco Cutolo, Maria Attanasio, Raffaele Lieto, Filomena Morisco
Journal of Clinical Medicine.2023; 12(13): 4316. CrossRef
Prevalence and Prognostic Significance of Liver Fibrosis in Patients With Aneurysmal Subarachnoid Hemorrhage
Tiangui Li, Peng Wang, Xiao Gong, Weelic Chong, Yang Hai, Chao You, Juan Kang, Fang Fang, Yu Zhang
Frontiers in Neurology.2022;[Epub] CrossRef

Clinical Study
Development of a Non-Invasive Liver Fibrosis Score Based on Transient Elastography for Risk Stratification in Patients with Type 2 Diabetes: Chi-Ho Lee, Wai-Kay Seto, Kelly Ieong, David T.W. Lui, Carol H.Y. Fong, Helen Y. Wan, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Karen S.L. Lam; Endocrinol Metab. 2021;36(1):134-145. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.887

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Background
In non-alcoholic fatty liver disease (NAFLD), transient elastography (TE) is an accurate non-invasive method to identify patients at risk of advanced fibrosis (AF). We developed a diabetes-specific, non-invasive liver fibrosis score based on TE to facilitate AF risk stratification, especially for use in diabetes clinics where TE is not readily available.
Methods
Seven hundred sixty-six adults with type 2 diabetes and NAFLD were recruited and randomly divided into a training set (n=534) for the development of diabetes fibrosis score (DFS), and a testing set (n=232) for internal validation. DFS identified patients with AF on TE, defined as liver stiffness (LS) ≥9.6 kPa, based on a clinical model comprising significant determinants of LS with the lowest Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NFS, FIB-4, and APRI), using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (NPV).
Results
DFS comprised body mass index, platelet, aspartate aminotransferase, high-density lipoprotein cholesterol, and albuminuria, five routine measurements in standard diabetes care. Derived low and high DFS cut-offs were 0.1 and 0.3, with 90% sensitivity and 90% specificity, respectively. Both cut-offs provided better NPVs of >90% than conventional fibrosis scores. The AUROC of DFS for AF on TE was also higher (P<0.01) than the conventional fibrosis scores, being 0.85 and 0.81 in the training and testing sets, respectively.
Conclusion
Compared to conventional fibrosis scores, DFS, with a high NPV, more accurately identified diabetes patients at-risk of AF, who need further evaluation by hepatologists.

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Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes—A real‐world study
Chi‐Ho Lee, David Tak‐Wai Lui, Lung‐Yi Mak, Carol Ho‐Yi Fong, Kylie Sze‐Wing Chan, Jimmy Ho‐Cheung Mak, Chloe Yu‐Yan Cheung, Wing‐Sun Chow, Yu‐Cho Woo, Man‐Fung Yuen, Wai‐Kay Seto, Karen Siu‐Ling Lam
Diabetes, Obesity and Metabolism.2025; 27(2): 574. CrossRef
Moving diagnosis of liver fibrosis into the community
Elisa Pose, Salvatore Piano, Maja Thiele, Núria Fabrellas, Emmanuel A. Tsochatzis, Pere Ginès
Journal of Hepatology.2025; 83(1): 258. CrossRef
Implementation of a liver health check in people with type 2 diabetes
Kushala W M Abeysekera, Luca Valenti, Zobair Younossi, John F Dillon, Alina M Allen, Mazen Noureddin, Mary E Rinella, Frank Tacke, Sven Francque, Pere Ginès, Maja Thiele, Philip N Newsome, Indra Neil Guha, Mohammed Eslam, Jörn M Schattenberg, Saleh A Alqa
The Lancet Gastroenterology & Hepatology.2024; 9(1): 83. CrossRef
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease
Chi-Ho Lee, David Tak-Wai Lui, Raymond Hang-Wun Li, Michele Mae-Ann Yuen, Carol Ho-Yi Fong, Ambrose Pak-Wah Leung, Justin Chiu-Man Chu, Loey Lung-Yi Mak, Tai-Hing Lam, Jean Woo, Yu-Cho Woo, Aimin Xu, Hung-Fat Tse, Kathryn Choon-Beng Tan, Bernard Man-Yung
Frontiers in Endocrinology.2023;[Epub] CrossRef
Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review
Luca Rinaldi, Chiara Giorgione, Andrea Mormone, Francesca Esposito, Michele Rinaldi, Massimiliano Berretta, Raffaele Marfella, Ciro Romano
Viruses.2023; 15(8): 1730. CrossRef
Metabolic dysfunction-associated fatty liver disease — How relevant is this to primary care physicians and diabetologists?
Chi-Ho Lee
Primary Care Diabetes.2022; 16(2): 245. CrossRef
Non‐alcoholic fatty liver disease and type 2 diabetes: An update
Chi‐H Lee, David TW Lui, Karen SL Lam
Journal of Diabetes Investigation.2022; 13(6): 930. CrossRef
Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes
Georgiana-Diana Cazac, Cristina-Mihaela Lăcătușu, Cătălina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
Biomedicines.2022; 10(10): 2375. CrossRef

Endocrine Research
Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice: Dae Hyun Kim, Ye Ra Kim, EunJin Bang, Sugyeong Ha, Sang Gyun Noh, Byeong Moo Kim, Seong Ho Jeong, Hee Jin Jung, Ji Young Lee, Hae Young Chung; Endocrinol Metab. 2021;36(1):171-184. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.850

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Background
Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated.
Methods
To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD).
Results
Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups.
Conclusion
Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.

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Peng Zhang, Naicheng Liu, Mingyang Xue, Mengjie Zhang, Zidong Xiao, Chen Xu, Yuding Fan, Junqiang Qiu, Qinghua Zhang, Yong Zhou
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Gal Reches, Ron Piran
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Min Hi Park, Dae Hyun Kim
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Gabriella Meier Bürgisser, Olivera Evrova, Dorothea M. Heuberger, Julia Rieber, Pietro Giovanoli, Maurizio Calcagni, Johanna Buschmann
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Review Articles

Diabetes, Obesity and Metabolism
Metabolically Healthy and Unhealthy Normal Weight and Obesity: Norbert Stefan; Endocrinol Metab. 2020;35(3):487-493. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.301

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Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

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Diabetes, Obesity and Metabolism
Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease: Dae Ho Lee; Endocrinol Metab. 2020;35(2):243-259. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.243

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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver diseases and can progress to advanced fibrosis and end-stage liver disease. Thus, intensive research has been performed to develop noninvasive methods for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis. Currently, no single noninvasive tool covers all of the stages of pathologies and conditions of NAFLD, and the cost and feasibility of known techniques are also important issues. Blood biomarkers for NAFLD may be useful to select subjects who need ultrasonography (US) screening for NAFLD, and noninvasive tools for assessing fibrosis may be helpful to exclude the probability of significant fibrosis and to predict advanced fibrosis, thus guiding the decision of whether to perform liver biopsy in patients with NAFLD. Among various methods, magnetic resonance-based methods have been shown to perform better than other methods in assessing steatosis as well as in detecting hepatic fibrosis. Many genetic markers are associated with the development and progression of NAFLD. Further well-designed studies are needed to determine which biomarker panels, imaging studies, genetic marker panels, or combinations thereof perform well for diagnosing NAFLD, differentiating NASH and fibrosis, and following-up NAFLD, respectively.

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Original Article

Clinical Study
Visceral-to-Subcutaneous Abdominal Fat Ratio Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis: Chan-Hee Jung, Eun-Jung Rhee, Hyemi Kwon, Yoosoo Chang, Seungho Ryu, Won-Young Lee; Endocrinol Metab. 2020;35(1):165-176. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.165

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Background

We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.

Methods

This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.

Results

The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.

Conclusion

High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.

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Namgok Lecture 2019

Diabetes, Obesity and Metabolism
Impact of Skeletal Muscle Mass on Metabolic Health: Gyuri Kim, Jae Hyeon Kim; Endocrinol Metab. 2020;35(1):1-6. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.1

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Abstract PDF PubReader ePub

Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.

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Review Article

Diabetes, Obesity and Metabolism
Nonalcoholic Fatty Liver Disease and Diabetes: An Epidemiological Perspective: Eun-Jung Rhee; Endocrinol Metab. 2019;34(3):226-233. Published online September 26, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.3.226

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Abstract PDF PubReader ePub

Nonalcoholic fatty liver disease (NAFLD) is thought to stem from the body's inability to store excess energy in adipocytes; as such, it is commonly viewed as the hepatic manifestation of metabolic syndrome. The pathogenesis of NAFLD involves ectopic fat accumulation, which also takes place in the liver, muscle and visceral fat. NAFLD is rapidly becoming more widespread in Korea, with an estimated prevalence of 30% in adults. Type 2 diabetes mellitus (T2DM) and NAFLD share insulin resistance as a common pathophysiological mechanism, and each of these two diseases affects the development of the other. Recent studies have suggested that NAFLD is often present as a comorbidity in T2DM patients. The mutual interrelationship between these conditions is shown by findings suggesting that T2DM can exacerbate NAFLD by promoting progression to nonalcoholic hepatosteatosis or fibrosis, while NAFLD causes the natural course of diabetic complications to worsen in T2DM patients. It remains unknown whether one disease is the cause of the other or vice versa. In this review, I would like to discuss current epidemiological data on the associations between NAFLD and T2DM, and how each disease affects the course of the other.

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Original Article

Clinical Study
Triglyceride Glucose Index Is Superior to the Homeostasis Model Assessment of Insulin Resistance for Predicting Nonalcoholic Fatty Liver Disease in Korean Adults: Sang Bae Lee, Min Kyung Kim, Shinae Kang, Kahui Park, Jung Hye Kim, Su Jung Baik, Ji Sun Nam, Chul Woo Ahn, Jong Suk Park; Endocrinol Metab. 2019;34(2):179-186. Published online May 20, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.179

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Abstract PDF PubReader ePub

Background

Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults.

Methods

Participants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography.

Results

Significant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend <0.01), respectively. According to the receiver operating characteristic analysis, the TyG index was superior to HOMA-IR in predicting NAFLD.

Conclusion

The TyG index and prevalence of NAFLD were significantly related and the TyG index was superior to HOMA-IR in predicting NAFLD in Korean adults.

Citations

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Obesity Surgery.2026; 36(5): 2442. CrossRef
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Frontiers in Nutrition.2026;[Epub] CrossRef
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The Kaohsiung Journal of Medical Sciences.2026;[Epub] CrossRef
TyG index combined with BMI predicts metabolism dysfunction-associated fatty liver disease in patients with type 2 diabetes
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Open Medicine.2026;[Epub] CrossRef
Triglyceride-glucose index as a predictor of body composition changes in patients undergoing bariatric surgery
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Scientific Reports.2026;[Epub] CrossRef
Association between the C-reactive protein-triglyceride glucose index and erectile dysfunction in US males: results from NHANES 2001–2004
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International Journal of Impotence Research.2025; 37(8): 612. CrossRef
Triglyceride-glucose index as a marker for visceral obesity in patients with gastric cancer
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Frontiers in Nutrition.2025;[Epub] CrossRef
The Prognostic Value of the Triglyceride-Glucose and Fibrosis-4 Indices in Patients Undergoing Coronary Angiography: A Retrospective Cohort Analysis
Amir Aker, Tom Tarchitzky, Yuval Avidan, Barak Zafrir
CJC Open.2025; 7(4): 465. CrossRef
Prediction of MASLD using different screening indexes in Chinese type 2 diabetes mellitus
Mengmeng Hu, Jingyu Yang, Beibei Gao, Zhoulu Wu, Ying Wu, Dandan Hu, Qiong Shen, Lei Chen
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
Predictive Value of the Triglyceride-Glucose Index for Metabolic-Associated Fatty Liver Disease in Individuals with Different Metabolic Obese Phenotypes
Dan Lv, Zepu Wang, Huanxin Liu, Cuiqiao Meng
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 125. CrossRef
Use of the FHTHWA Index as a Novel Approach for Predicting the Incidence of Diabetes in a Japanese Population Without Diabetes: Data Analysis Study
Jiao Wang, Jianrong Chen, Ying Liu, Jixiong Xu
JMIR Medical Informatics.2025; 13: e64992. CrossRef
The predictive value of triglyceride-glucose-high density lipoprotein-body mass index (TGH-BMI) for different degrees of hepatic steatosis and liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD)
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Clinical Nutrition ESPEN.2025; 66: 290. CrossRef
Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents
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Diabetes & Metabolism Journal.2025; 49(2): 264. CrossRef
The Value of TyG‐Related Indices in Evaluating MASLD and Significant Liver Fibrosis in MASLD
Haoxuan Zou, Jiejie Xie, Xiaopu Ma, Yan Xie, Xingshun Qi
Canadian Journal of Gastroenterology and Hepatology.2025;[Epub] CrossRef
Association of triglyceride-glucose index with bone mineral density and fracture: a systematic review
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Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
The triglyceride glucose-waist circumference is the best indicator for screening non-alcoholic fatty liver disease in middle-aged and elderly people
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Nutrición Hospitalaria.2025;[Epub] CrossRef
Triglyceride-glucose index is independently associated with fatty pancreas disease in Chinese elderly
Weinuo Mi, Yuzhi Zhang, Qifeng Wang, Wenbo Ding, Xiaodong Mao, Yu Sun, Xingjia Li, Chao Liu, Shuhang Xu
BMC Endocrine Disorders.2025;[Epub] CrossRef
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Derya Kalyoncu, Melis Kavrak Kursun
BMC Endocrine Disorders.2025;[Epub] CrossRef
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BMC Gastroenterology.2025;[Epub] CrossRef
Association of Triglyceride-Glucose (TyG) Index With Severe Acute Pancreatitis: A Systematic Review and Meta-Analysis
Roshan K Mahat, Vedika Rathore, Ravindra Saxena
Cureus.2025;[Epub] CrossRef
Triglyceride-glucose parameters as predictors of diabetes mellitus incidence in Korean adults: a secondary analysis of a Prospective Cohort Study
Yu Jin Park, Miseon Shin, Hyun Seon Jeon, Eun Hee Yang
Journal of Korean Academy of Nursing.2025; 55(2): 205. CrossRef
Potential utility of the triglyceride-glucose index as a predictor of erectile dysfunction and its severity: a cross-sectional, case–control study
Huseyin Aytac Ates, Taha Burak Bulut
Scientific Reports.2025;[Epub] CrossRef
Relationship between triglyceride-glucose index and stroke risk in middle-aged and older Chinese population: a national longitudinal study based on explainable machine learning
Ying Gao, Meihui Zhang, Chen Xu, Birong Wu, Shan Qiao, Yong Cai, Fan Hu
Diabetes Research and Clinical Practice.2025; 227: 112414. CrossRef
Gender differences in the association between the triglyceride-glucose index and peripheral artery disease in vascular surgery inpatients aged 50 and above: a retrospective cross-sectional study
Zhi-wei Li, Peng Zhou, Bei-hao Shi, Ya-qin Gong, Ke Lu, Jian Zhu
Frontiers in Endocrinology.2025;[Epub] CrossRef
Impact of genotyping (PTPN2, rs2542151) and (MBOAT7, rs641738) in prediction of fibrosis in Metabolic dysfunction- associated steatotic liver disease’ patients
Shimaa Abdelsattar, Hiba S. Al-Amodi, Hala F. M. Kamel, Zeinab A. Kasemy, Ehab Darwish, Asmaa Mosbeh, Ayman A. Sakr, Hanaa M. Elgazzar, Mervat Abdelkareem, Mai Abozeid, Shimaa K. Zewain, Hanan M. Bedair, Sabry M. Abdelmageed
Frontiers in Endocrinology.2025;[Epub] CrossRef
Associations of triglyceride-glucose index with N-terminal pro-B-type natriuretic peptide and mortality in middle-aged and elderly individuals
Haitao Xie, Le Shen, Jianghong Li, Chuxin Lv, Tong Sun, Peng Yu, Xiaohu Chen, Shuhua Tang
Frontiers in Endocrinology.2025;[Epub] CrossRef
Association between the TyG index and MAFLD and its subtypes: a population-based cross-sectional study
Cui’e Liu, Chaochen Li, Jia Fu, Long Bai, Man Wang, Pei Song, Meng Zheng
BMC Gastroenterology.2025;[Epub] CrossRef
Novel surrogate markers of insulin resistance in patients with metabolic dysfunction-associated steatosis liver disease: Associations with dietary and lifestyle inflammatory scores in the large cross-sectional study
Yusuf Yilmaz, Behrad Saeedian, Nastaran Babajani, Sara Ashtari, Fereshteh Ghorat, Ehsaneh Taheri
Clinical Nutrition ESPEN.2025; 70: 204. CrossRef
Landscape and research trends of triglyceride-glucose index with health: a bibliometric analysis
Jia Liu, Song Hu, Shan Wang, Tongxiao Luan, Yuting Duan, Nina An, Jing Zhou, Li Jia, Yongjun Mao
Discover Medicine.2025;[Epub] CrossRef
The Predictive Role of the Triglyceride/High-Density Lipoprotein Ratio and the Triglyceride–Glucose Index, Along with Anthropometric Measurements, in Diagnosing Non-Alcoholic Fatty Liver Disease in Obese Kids and Juveniles, and the Evaluation of Novel Car
Emrah Çığrı, Funda Çatan İnan, Sedat Gülten, Mehmet Akif Bildirici, Ayşe Ece Gökkaya, Metin Asıleren, Mustafa Koyun, Bahadır Reis, Merve Esen
Children.2025; 12(11): 1439. CrossRef
Associations of longitudinal trajectories of triglyceride-glucose index combined with classical and novel obesity indices and cardiovascular disease: evidence from a nationwide prospective cohort study in China
Chao Wang, Shiming He, Guobo Xie, Shuhua Zhang, Zhiyu Xiong, Hengcheng Lu, Qun Wang, Lin Xie, Wei Wang, Yang Zou, Xue Li
Cardiovascular Diabetology.2025;[Epub] CrossRef
High triglyceride-glucose index is associated with diabetes mellitus in people with HIV in Southwest China
Liangjia Wei, Chunxing Tao, Xinju Huang, Ruby Congjiang Wang, Jianhua Che, Aidan Nong, Rongye Huang, Zhiman Yan, Lijing Huang, Jiao Qin, Lincong Chen, Sanqi An, Junjun Jiang, Lixian Xiong, Hao Liang, Lijuan Bao, Bingyu Liang, Li Ye
AIDS.2025; 39(15): 2295. CrossRef
Assessing the role of the Triglyceride-glucose related indices in identifying metabolic syndrome risk across body mass index categories
Chengcheng Qian, Liling Mao, Yu Liu, Xinxin Zhao, Jin Li, Fei Sheng, Haoming Song
Endocrine.2025;[Epub] CrossRef
Comparison of the TyG index, TyG-traditional obesity indices, and TyG-novel obesity indices: does increased complexity help in predicting cardiometabolic multimorbidity?
Fanzhi Zhang, Bin Zhang, Xinfang Huang, Zhenyu Wang, Juan Wang, Houhui Lan, Guobo Xie, Wei Wang, Yang Zou, Chao Wang
Lipids in Health and Disease.2025;[Epub] CrossRef
Triglyceride-glucose body mass index predicts prognosis in patients with ST-elevation myocardial infarction
Ming Liu, Jianyuan Pan, Ke Meng, Yuwei Wang, Xueqing Sun, Likun Ma, Xiaofan Yu
Scientific Reports.2024;[Epub] CrossRef
Triglyceride-glucose index is capable of identifying metabolically obese, normal-weight older individuals
Bokun Kim, Keisuke Taniguchi, Tomonori Isobe, Sechang Oh
Journal of Physiological Anthropology.2024;[Epub] CrossRef
Comparison of triglyceride/glucose index and related parameters with Indian Diabetes Risk Score assessment in non-diabetic individuals visiting primary healthcare centre—A community-based cross-sectional study
Sivapragasam Ramalingam, Amlan Kumar Kar, Rajini Senthil
Journal of Family Medicine and Primary Care.2024; 13(1): 235. CrossRef
Insulin resistance in NSCLC: unraveling the link between development, diagnosis, and treatment
Shizhang Zhan, Liu Wang, Wenping Wang, Ruoran Li
Frontiers in Endocrinology.2024;[Epub] CrossRef
The association between the triglyceride–glucose index and prognosis in postoperative renal cell carcinoma patients: a retrospective cohort study
Guoliang Qin, Zhuang Sun, Yuxiang Jin, Xiangguo Ren, Zhaocun Zhang, Shuo Wang, Guanwen Zhou, Kun Huang, Haifeng Zhao, Xianzhou Jiang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Profiling triglyceride-glucose index in Filipinos with type 2 diabetes mellitus: a single-center study
Chastene Christopher Flake, Madonna Morales-Valenzuela, Raphael Enrique Tiongco, Annalyn Navarro
The Egyptian Journal of Internal Medicine.2024;[Epub] CrossRef
Diagnostic Performance of Insulin Resistance Indices for Identifying Metabolic Dysfunction–Associated Fatty Liver Disease
A. Lum Han, Hee Kyung Lee, Sae Ron Shin
Metabolic Syndrome and Related Disorders.2024; 22(5): 402. CrossRef
Metabolic profiling of galectin-1 and galectin-3: a cross-sectional, multi-omics, association study
Emanuel Fryk, Vagner Ramon Rodrigues Silva, Lena Strindberg, Robin Strand, Håkan Ahlström, Karl Michaëlsson, Joel Kullberg, Lars Lind, Per-Anders Jansson
International Journal of Obesity.2024; 48(8): 1180. CrossRef
A Study of the Relationship Between the Triglyceride-Glucose Index and Skeletal Muscle Mass in a General Chinese Population
Yue Liu, Hongwei Chen, Ziyi Wei, Tingting Han, Ningxin Chen, Yurong Weng, Yaomin Hu
Clinical Medicine Insights: Endocrinology and Diabetes.2024;[Epub] CrossRef
Triglyceride–glucose–alanine aminotransferase index: A noninvasive serum predictor for identifying the severity of pediatric nonalcoholic fatty liver disease
Eu-Seon Noh, Il Tae Hwang
Medicine.2024; 103(26): e38241. CrossRef
Triglyceride glucose index as a predictor for non-alcoholic fatty liver disease: insights from a longitudinal analysis in non-obese individuals
Qi Ning, Keyang Zheng, Jiafu Yan, Chao Zhu
Frontiers in Medicine.2024;[Epub] CrossRef
The nutritional metabolic risk index as a predictor of all-cause and cardiovascular mortality: A national cohort study
Chuanwei Zhao, Yane Yang, Conghao Duan, Chenxuan Gao, Yansi Wang, Huan Ni, Lanping Zhou, Yunfang Xiang, MeiJu Li, Zhao Xu
Clinical Nutrition ESPEN.2024; 63: 391. CrossRef
Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease
Bitgyeol Kim, Hye Young Jin, Jong Seo Yoon, Eu Seon Noh, Il Tae Hwang
Journal of Clinical Research in Pediatric Endocrinology.2024;[Epub] CrossRef
Triglyceride-glucose index and combined indicators: effective indicators for screening NAFLD in snoring patients
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BMC Pulmonary Medicine.2024;[Epub] CrossRef
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Sandeep Samethadka Nayak, Dona Kuriyakose, Lakshmi D. Polisetty, Anjali Avinash Patil, Daniyal Ameen, Rakshita Bonu, Samatha P. Shetty, Pubali Biswas, Micheal T. Ulrich, Negin Letafatkar, Arman Habibi, Mohammad-Hossein Keivanlou, Sara Nobakht, Abdulhadi A
Cardiovascular Diabetology.2024;[Epub] CrossRef
Relationship between triglyceride-glucose index and endometriosis: a cross-sectional analysis
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BMC Women's Health.2024;[Epub] CrossRef
Association Between Triglyceride-Glucose Index and Lung Function Parameters in the General Population Undergoing Health Examinations
Yu Yang, Shuqi Wang, Boying Jia, Shuchun Chen
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 4031. CrossRef
Association of HOMA-IR Versus TyG Index with Diabetes in Individuals Without Underweight or Obesity
Bokun Kim, Gwon-Min Kim, Up Huh, Juhyun Lee, Eunji Kim
Healthcare.2024; 12(23): 2458. CrossRef
The Triglyceride-Glucose Index is Associated with Vitamin D Status in Metabolic-Associated Fatty Liver Disease
Zhiping Liu, Wensha Zhang, Zhiwei Zhao, Wenhao Li, Jinhua Zhang
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2651. CrossRef
The triglyceride and glucose index and risk of nonalcoholic fatty liver disease: A dose–response meta-analysis
Qin Ling, Jiawei Chen, Xiao Liu, Yi Xu, Jianyong Ma, Peng Yu, Kai Zheng, Fuwei Liu, Jun Luo
Frontiers in Endocrinology.2023;[Epub] CrossRef
Triglyceride–Glucose Index as a Potential Indicator of Sarcopenic Obesity in Older People
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Nutrients.2023; 15(3): 555. CrossRef
Association of insulin resistance with bone mineral density in a nationwide health check-up population in China
Ming Zhuo, Ze Chen, Mao-Lin Zhong, Fang Lei, Juan-Juan Qin, Shuhua Liu, Ye-Mao Liu, Tao Sun, Xiao-Jing Zhang, Lihua Zhu, Jingjing Cai, Jun-Ming Ye, Erping Yang
Bone.2023; 170: 116703. CrossRef
Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes & Metabolism Journal.2023; 47(2): 220. CrossRef
Comparison of the prognostic value of a comprehensive set of predictors in identifying risk of metabolic-associated fatty liver disease among employed adults
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BMC Public Health.2023;[Epub] CrossRef
The triglyceride glucose index and CDKAL1 gene rs10946398 SNP are associated with NAFLD in Chinese adults
Jun ZHU, Dujuan XU, Ruihua YANG, Min LIU, Ying LIU
Minerva Endocrinology.2023;[Epub] CrossRef
PNPLA3 rs738409 risk genotype decouples TyG index from HOMA2-IR and intrahepatic lipid content
Ákos Nádasdi, Viktor Gál, Tamás Masszi, Anikó Somogyi, Gábor Firneisz
Cardiovascular Diabetology.2023;[Epub] CrossRef
Baseline level and change trajectory of the triglyceride-glucose index in relation to the development of NAFLD: a large population-based cohort study
Yaqin Wang, Jiangang Wang, Lei Liu, Pingting Yang, Shuwen Deng, Xuelian Liu, Linlin Zhao, Changfa Wang, Ying Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Assessing temporal differences in the predictive power of baseline TyG-related parameters for future diabetes: an analysis using time-dependent receiver operating characteristics
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Journal of Translational Medicine.2023;[Epub] CrossRef
Metabolic Score for Insulin Resistance (METS-IR) Predicts Adverse Cardiovascular Events in Patients with Type 2 Diabetes and Ischemic Cardiomyopathy
Xuehe Zhang, Fen Liu, Wenling Li, Jixin Zhang, Tong Zhang, Xiaolin Yu, Junyi Luo, Qian Zhao, Jinyu Zhang, Binbin Fang, Yining Yang, Xiaomei Li
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1283. CrossRef
Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease Among Hospital Staff
Daya Zhang, Lijun Zhang, Shiju Chen, Runxiang Chen, Xiaodong Zhang, Feihu Bai
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1221. CrossRef
The metabolic score of insulin resistance is positively correlated with bone mineral density in postmenopausal patients with type 2 diabetes mellitus
Peng Gu, Bin Pu, Qiao Xin, Dan Yue, LieLiang Luo, JiaSheng Tao, HaiShan Li, Ming Chen, MingHua Hu, XiaoRong Hu, XiaoHui Zheng, ZhanPeng Zeng
Scientific Reports.2023;[Epub] CrossRef
Prevalence estimates of the insulin resistance and associated prevalence of heart failure among United Status adults
Xiaozhong Li, Jihong Wang, Liyan Niu, Ziqi Tan, Jianyong Ma, Ling He, Peng Yu, Xiao Liu, Juxiang Li
BMC Cardiovascular Disorders.2023;[Epub] CrossRef
From NAFLD to HCC: Advances in noninvasive diagnosis
Qinchen Xu, Maoxiao Feng, Yidan Ren, Xiaoyan Liu, Huiru Gao, Zigan Li, Xin Su, Qin Wang, Yunshan Wang
Biomedicine & Pharmacotherapy.2023; 165: 115028. CrossRef
Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents
Jong Seo Yoon, Kyoung Ja Lim, Il Tae Hwang
Scientific Reports.2023;[Epub] CrossRef
A non-linear relationship between triglyceride glucose waist circumference and nonalcoholic fatty liver disease in a Japanese population: a secondary analysis
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Frontiers in Endocrinology.2023;[Epub] CrossRef
Neck Circumference as a Predictor of Insulin Resistance in People with Non-alcoholic Fatty Liver Disease
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Journal of Obesity & Metabolic Syndrome.2023; 32(3): 214. CrossRef
Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Insulin Resistance-Related Indices in the Japanese Population
Kengo Moriyama, Nagamu Inoue, Jin Imai, Yumi Masuda, Chizumi Yamada, Noriaki Kishimoto, Shinji Takashimizu, Akira Kubo, Yasuhiro Nishizaki
Metabolic Syndrome and Related Disorders.2023; 21(9): 489. CrossRef
Application value of triglyceride-glucose index and triglyceride-glucose body mass index in evaluating the degree of hepatic steatosis in non-alcoholic fatty liver disease
Mengyuan Wang, Mingxing Chang, Peipu Shen, Wei Wei, Huayao Li, Guifang Shen
Lipids in Health and Disease.2023;[Epub] CrossRef
Homeostatic Model Assessment of Insulin Resistance as a Potential Screening Test for Non-Alcoholic Fatty Liver Disease in Korean Adults without Diabetes
Hyejung Lee, Jae-Ho Lee
Korean Journal of Family Practice.2023; 13(4): 233. CrossRef
Comparison of the Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict Nonalcoholic Fatty Liver Disease in Youths
Kyungchul Song, Goeun Park, Hye Sun Lee, Myeongseob Lee, Hae In Lee, Han Saem Choi, Junghwan Suh, Ahreum Kwon, Ho-Seong Kim, Hyun Wook Chae
The Journal of Pediatrics.2022; 242: 79. CrossRef
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Ehsaneh Taheri, Mohammad Amin Pourhoseingholi, Alireza Moslem, Amir Hossein Hassani, Alireza Mousavi Jarrahi, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Behzad Hatami
Journal of Diabetes & Metabolic Disorders.2022; 21(1): 97. CrossRef
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Nutrition, Metabolism and Cardiovascular Diseases.2022; 32(3): 596. CrossRef
Triglycerides/Glucose Index Is Associated with Sperm Parameters and Sperm DNA Fragmentation in Primary Infertile Men: A Cross-Sectional Study
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Metabolites.2022; 12(2): 143. CrossRef
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Xiaomeng Yang, Guangyao Wang, Jing Jing, Anxin Wang, Xiaoli Zhang, Qian Jia, Xia Meng, Xingquan Zhao, Liping Liu, Hao Li, Yongjun Wang, Yilong Wang
BMC Neurology.2022;[Epub] CrossRef
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Diabetes & Metabolism.2022; 48(4): 101345. CrossRef
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Diabetes and Vascular Disease Research.2022;[Epub] CrossRef
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Journal of Clinical Medicine.2022; 11(9): 2666. CrossRef
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Journal of Clinical Medicine.2022; 11(11): 3043. CrossRef
Triglyceride glucose index is superior biomarker for predicting type 2 diabetes mellitus in children and adolescents
Jong Seo Yoon, Hye Jin Lee, Hwal Rim Jeong, Young Suk Shim, Min Jae Kang, Il Tae Hwang
Endocrine Journal.2022; 69(5): 559. CrossRef
Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
Obesity.2022; 30(6): 1279. CrossRef
Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
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Journal of General Internal Medicine.2022; 37(16): 4153. CrossRef
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Journal of Clinical Medicine.2022; 11(13): 3649. CrossRef
Comparison of the diagnostic value between triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio in metabolic-associated fatty liver disease patients: a retrospective cross-sectional study
Zhi Liu, He He, Yuzhao Dai, Lidan Yang, Shenling Liao, Zhenmei An, Shuangqing Li
Lipids in Health and Disease.2022;[Epub] CrossRef
Insulin Resistance Markers to Detect Nonalcoholic Fatty Liver Disease in a Male Hispanic Population
Maritza Pérez-Mayorga, Jose P. Lopez-Lopez, Maria A. Chacon-Manosalva, Maria G Castillo, Johanna Otero, Daniel Martinez-Bello, Diego Gomez-Arbelaez, Daniel D. Cohen, Patricio Lopez-Jaramillo, Federico Ravaioli
Canadian Journal of Gastroenterology and Hepatology.2022; 2022: 1. CrossRef
Risk factors and prediction model for nonalcoholic fatty liver disease in northwest China
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Scientific Reports.2022;[Epub] CrossRef
The triglyceride glucose index is associated with the cerebral small vessel disease in a memory clinic population
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Journal of Clinical Neuroscience.2022; 104: 126. CrossRef
Integrating experimental model, LC-MS/MS chemical analysis, and systems biology approach to investigate the possible antidiabetic effect and mechanisms of Matricaria aurea (Golden Chamomile) in type 2 diabetes mellitus
Yassin Ismail, Dina M. Fahmy, Maivel H. Ghattas, Mai M. Ahmed, Walaa Zehry, Samy M. Saleh, Dina M. Abo-elmatty
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Review Article

Diabetes, Obesity and Metabolism
Implications of Mitochondrial Unfolded Protein Response and Mitokines: A Perspective on Fatty Liver Diseases: Hyon-Seung Yi; Endocrinol Metab. 2019;34(1):39-46. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.39

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The signaling network of the mitochondrial unfolded protein response (UPR^mt) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPR^mt is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPR^mt and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPR^mt and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

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Original Article

Clinical Study
Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease: Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Bo-Yeon Kim; Endocrinol Metab. 2018;33(3):387-394. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.387

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Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin.

Methods

Among patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed.

Results

A total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (−2.9 kg vs. −0.4 kg, P=0.005; −21.1 U/L vs. −9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046).

Conclusion

ALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Citations

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Review Articles

Diabetes, Obesity and Metabolism
Association of Adipokines with Development and Progression of Nonalcoholic Fatty Liver Disease: Chrysoula Boutari, Nikolaos Perakakis, Christos Socrates Mantzoros; Endocrinol Metab. 2018;33(1):33-43. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.33

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Abstract PDF PubReader ePub

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting 30% of the general population and 40% to 70% of obese individuals. Adipose tissue plays a crucial role in its pathogenesis, as it produces and secretes pro- and anti-inflammatory cytokines called adipokines. Adiponectin and leptin have well-determined actions in terms of NAFLD pathophysiology. Adiponectin deficiency is associated with a pro-inflammatory condition, as it is observed in obesity and other metabolic disorders. On the other hand, increased leptin levels, above the normal levels, act as a pro-inflammatory stimulus. Regarding other adipokines (resistin, visfatin, chemerin, retinol-binding protein 4, irisin), data about their contribution to NAFLD pathogenesis and progression are inconclusive. In addition, pharmacological agents like thiazolidinediones (pioglitazone and rosiglitazone), that are used in the management of NAFLD exert favourable effects on adipokine levels, which in turn may contribute to the improvement of liver function. This review summarizes the current knowledge and developments in the association between adipokines and NAFLD and discusses possible therapeutic implications targeting the modulation of adipokine levels as a potential tool for the treatment of NAFLD.

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The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis: Young-Ah Moon; Endocrinol Metab. 2017;32(1):6-10. Published online January 19, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.6

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Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, obesity, and dyslipidemia. NAFLD encompasses a wide range of states from the simple accumulation of triglycerides in the hepatocytes to serious states accompanied by inflammation and fibrosis in the liver. De novo lipogenesis has been shown to be a significant factor in the development of hepatic steatosis in insulin-resistant states. Sterol regulatory element binding protein-1c (SREBP-1c) is the main transcription factor that mediates the activation of lipogenesis, and SREBP cleavage activating protein (SCAP) is required for the activation of SREBPs. Here, recent animal studies that suggest SCAP as a therapeutic target for hepatic steatosis and hypertriglyceridemia are discussed.

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Diabetes, Obesity and Metabolism
Bile Acid Nuclear Receptor Farnesoid X Receptor: Therapeutic Target for Nonalcoholic Fatty Liver Disease: Sun-Gi Kim, Byung-Kwon Kim, Kyumin Kim, Sungsoon Fang; Endocrinol Metab. 2016;31(4):500-504. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.500

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Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure. The main causes of NAFLD have not been revealed yet, metabolic syndromes including obesity and insulin resistance are widely accepted for the critical risk factors for the pathogenesis of NAFLD. Nuclear receptors (NRs) are transcriptional factors that sense environmental or hormonal signals and regulate expression of genes, involved in cellular growth, development, and metabolism. Several NRs have been reported to regulate genes involved in energy and xenobiotic metabolism and inflammation. Among various NRs, farnesoid X receptor (FXR) is abundantly expressed in the liver and a key regulator to control various metabolic processes in the liver. Recent studies have shown that NAFLD is associated with inappropriate function of FXR. The impact of FXR transcriptional activity in NAFLD is likely to be potential therapeutic strategy, but still requires to elucidate underlying potent therapeutic mechanisms of FXR for the treatment of NAFLD. This article will focus the physiological roles of FXR and establish the correlation between FXR transcriptional activity and the pathogenesis of NAFLD.

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Original Articles

Clinical Study
The Relationship between 10-Year Cardiovascular Risk Calculated Using the Pooled Cohort Equation and the Severity of Non-Alcoholic Fatty Liver Disease: Jeong In Lee, Min Chul Kim, Byung Sub Moon, Young Seok Song, Eun Na Han, Hyo Sun Lee, Yoonjeong Son, Jihyun Kim, Eun Jin Han, Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(1):86-92. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.86

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Background

We investigated the association between the severity of non-alcoholic fatty liver disease (NAFLD) and the estimated 10-year risk of cardiovascular disease (CVD) calculated by Pooled Cohort Equation (PCE) and Framingham risk score (FRS).

Methods

A total of 15,913 participants (mean age, 46.3 years) in a health screening program were selected for analysis. The presence and severity of fatty liver was assessed by abdominal ultrasonogram. Subjects who drank alcohol more than three times a week were excluded from the study.

Results

Among the participants, 57.6% had no NAFLD, 35.4% had grade I, 6.5% had grade II, and 0.5% had grade III NAFLD. Mean estimated 10-year CVD risk was 2.59%, 3.93%, 4.68%, and 5.23% calculated using the PCE (P for trend <0.01) and 4.55%, 6.39%, 7.33%, and 7.13% calculated using FRS, according to NAFLD severity from none to severe (P for trend <0.01). The odds ratio for ≥7.5% estimated CVD risk calculated using the PCE showed a higher correlation with increasing severity of NAFLD even after adjustment for conventional CVD risk factors (1.52, 2.56, 3.35 vs. the no NAFLD group as a reference, P<0.01) compared with calculated risk using FRS (1.65, 1.62, 1.72 vs. no NAFLD group as a reference, P<0.01).

Conclusion

In our study of apparently healthy Korean adults, increasing severity of NAFLD showed a higher correlation with estimated 10-year CVD risk when calculated using the PCE than when calculated using FRS.

Citations

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Clinical Study
Metabolic Health Is More Important than Obesity in the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Retrospective Study: Min-Kyung Lee, Eun-Jung Rhee, Min Chul Kim, Byung Sub Moon, Jeong In Lee, Young Seok Song, Eun Na Han, Hyo Sun Lee, Yoonjeong Son, Se Eun Park, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2015;30(4):522-530. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.522

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Background

The aim of this study is to compare the risk for future development of nonalcoholic fatty liver disease (NAFLD) according to different status of metabolic health and obesity.

Methods

A total of 3,045 subjects without NAFLD and diabetes at baseline were followed for 4 years. Subjects were categorized into four groups according to the following baseline metabolic health and obesity statuses: metabolically healthy, non-obese (MHNO); metabolically healthy, obese (MHO); metabolically unhealthy, non-obese (MUHNO); and metabolically unhealthy, obese (MUHO). Being metabolically healthy was defined as having fewer than two of the following five components: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostasis model assessment-insulin resistance index. Obesity was defined as a body mass index >25 kg/m². The presence of NAFLD was assessed by ultrasonography.

Results

The proportions of subjects included in the MHNO, MHO, MUHNO, and MUHO groups were 71.4%, 9.8%, 13.0%, and 5.8%, respectively. The proportions of subjects who developed NAFLD were 10.5%, 31.4%, 23.2%, and 42% in the MHNO, MHO, MUHNO, and MUHO groups, respectively. The risk for developing NAFLD was highest in subjects who were metabolically unhealthy both at baseline and after 4 years compared with subjects who were consistently metabolically healthy during the follow-up period (odds ratio, 2.862). Using the MHNO group as reference, the odds ratios for the MHO, MUHNO, and MUHO groups were 1.731, 1.877, and 2.501, respectively.

Conclusion

The risk for NAFLD was lower in MHO subjects than in MUNO subjects.

Citations

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Diabetes, Obesity and Metabolism
Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults: Dong Wook Jeong, Hye Won Lee, Young Hye Cho, Dong Won Yi, Sang Yeoup Lee, Seok Man Son, Yang Ho Kang; Endocrinol Metab. 2014;29(4):479-488. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.479

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Background

Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D₃ levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults.

Methods

A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D₃, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012.

Results

In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI ≥60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D₃, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D₃ level were observed in men. No significant differences in either serum ferritin or 25(OH)D₃ level were observed among women with different levels of severity of US-NAFLD.

Conclusion

Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

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Maternal vitamin D intake correlates with serum 25-Hydroxyvitamin D, Interleukin-6, and ferritin in maternal and umbilical cord
Yusrawati Yusrawati, Efrida Efrida, Nasrum Massi, Bahrul Fikri, Naoki Shimojo
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Serum 25-hydroxyvitamin D levels and the risk of non-alcoholic fatty liver
Qi Sheng, Huanchen Shi, Shousheng Liu, Likun Zhuang, Zhenzhen Zhao, Yongning Xin
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2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis
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Do Vitamin D Levels Affect Bone Mineral Density in Reproductive Women with Low Ferritin Levels?
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Ahmed A. Hassan, Mohiee E.-D.A. El-Aziz Awad, Hanan H. Soliman, Reda A.F. Usef, Dina S. Ata
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Diabetes, Obesity and Metabolism
Association of Serum Adipocyte-Specific Fatty Acid Binding Protein with Fatty Liver Index as a Predictive Indicator of Nonalcoholic Fatty Liver Disease: Won Seon Jeon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2013;28(4):283-287. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.283

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Background

Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects.

Methods

A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day).

Results

Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001). The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006). After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012).

Conclusion

This study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.

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Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
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FABP4 Expression in Subcutaneous Adipose Tissue Is Independently Associated with Circulating Triglycerides in Obesity
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Ricardo Rodríguez-Calvo, Juan Moreno-Vedia, Josefa Girona, Daiana Ibarretxe, Neus Martínez-Micaelo, Jordi Merino, Nuria Plana, Lluis Masana
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Yiting Xu, Xiaojing Ma, Xiaoping Pan, Xingxing He, Yufei Wang, Yuqian Bao
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Diabetes, Obesity and Metabolism
Tumor Necrosis Factor-α as a Predictor for the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Follow-Up Study: Yun Yong Seo, Yong Kyun Cho, Ji-Cheol Bae, Mi Hae Seo, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2013;28(1):41-45. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.41

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Background

Tumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study.

Methods

Three hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003.

Results

At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P<0.05). The risk of developing NAFLD was significantly greater in the highest tertile of TNF-α than in the lowest tertile after adjusting for age, smoking, and BMI (OR, 2.20; 95% confidence interval, 1.12 to 4.01; P<0.05).

Conclusion

Higher serum TNF-α levels in subjects without NAFLD were associated with the development of NAFLD. The results of study might suggest a pathologic role of inflammation in NAFLD.

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Free T4 is Negatively Correlated with Non-alcoholic Fatty Liver Disease in Euthyroid Women.: Eon Ju Jun, Hyun Sook Kim, Hyue Kyung Chung, Ji Hyun Lee, Sae Rom Kim, Eui Dal Jung; J Korean Endocr Soc. 2009;24(2):87-92. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.87

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Abstract PDF: BACKGROUND
Thyroid hormones play an important role in the regulation of lipid and carbohydrate metabolism and the body mass index (BMI), which all affect non-alcoholic fatty liver disease (NAFLD). In a previous study, we demonstrated that free T4 was negatively associated with the BMI in euthyroid women. However, there is still uncertain as to whether the thyroid function within the normal range is associated with NAFLD and liver function abnormalities. We sought to evaluate the thyroid function (free T4, TSH) and its possible relationship with NAFLD in euthyroid women. METHODS: A total of 835 euthyroid, non heavy alcoholics women who visited the Daegu Catholic University University Medical Centre for primary health screening from January 1, 2006 to December 31, 2006 participated in this cross-sectional study. The women who were not euthyroid or heavy alcoholics (> 70 g/week in women according to the DSM-IV), there was no known history of diabetes mellitus, the fasting blood glucose was more than 5.55 mmol/L and those who had viral hepatitis were excluded. Hepatic ultrasonography scanning was performed in all the participants by a single experienced radiologist. The TSH, free T4, BP, fasting glucose, serum liver enzymes (AST, ALT, GGT, T-bilirubin), lipid profiles [total-cholesterol, triglyceride (TG), HDL-C, LDL-C] and NAFLD were evaluated. RESULTS: Euthyroid women with NAFLD had lower free T4 levels than did the euthyroid women without NAFLD. After adjustment for age and BMI, free T4 was negatively correlated with TG, but free T4 was positively correlated with the total serum bilirubin. Free T4 was not correlated with the serum AST, ALT and GGT. After adjustment for age, the BMI, the fasting glucose, the GGT and free T4, but not TSH, were significantly negatively correlated with NAFLD. CONCLUSION: We demonstrated a negative correlation between free T4 and NAFLD in euthyroid women. This finding suggests lower levels of free T4 is associated with NAFLD in euthyroid subjects.

Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells.: Tae Sung Yun, Ae Kyung Min, Nam Kyung Kim, Mi Kyung Kim, Ho Chan Cho, Hye Soon Kim, Jae Seok Hwang, Seong Yeol Ryu, Keun Gyu Park, In Kyu Lee; J Korean Endocr Soc. 2008;23(1):27-34. Published online February 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.1.27

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Abstract PDF

BACKGROUND
Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression. METHODS: We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK). RESULTS: Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation. CONCLUSION: The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed.

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Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
Journal of Nutrition and Health.2015; 48(1): 1. CrossRef
Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
Journal of Nutrition and Health.2015; 48(1): 1. CrossRef

Association between Non-alcoholic Fatty Liver and Metabolic Diseases.: Hong Kyu Kim, Chan Jong Suh, Hyo Joong Yoon, Yong Ha Hwang, Kee Young Lee, Hye Young Park, Kap Hwan Kim, Moon Ho Kang; J Korean Endocr Soc. 2002;17(4):526-534. Published online August 1, 2002

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Abstract PDF: BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is known to be frequently associated with obesity, type 2 diabetes and dyslipidemia. Recently, the diagnosis of fatty liver disease, based on ultrasonographic findings, has increased. Therefore, we examined the association between NAFLD and various metabolic diseases, such as obesity, glucose intolerance, dyslipidemia, and hypertension or metabolic syndrome, and tried to find out whether NAFLD was independently related to insulin resistance. METHODS: From April to June 2000, 262 subjects, attending for routine physical check-ups, were screened. Of these, 115 one hundred fifteen subjects were studied, with the other 147 excluded due to significant alcohol consumption, evidence of viral or toxic hepatitis, significant liver or renal dysfunction, and overt thyroid disease. Fatty liver was diagnosed if the subject had a "bright" liver on ultrasonographic examination. All diagnoses were made by a single experienced radiologist. RESULTS: Of the 115 subjects. 30 (26%) showed NAFLD. 1. Systolic and diastolic blood pressures, body weight, serum total cholesterol, triglyceride, fasting insulin levels and HOMA IR (homeostasis model assessment insulin resistance index) were higher in the subjects with NAFLD than in the controls. 2. Multiple logistic regression analysis, including age, sex, BMI, waist to hip ratio, fasting serum glucose, lipids and insulin levels, HOMA IR, and hypertension showed that BMI, total cholesterol and HOMA IR were independently related with NAFLD. 3. 27% of the subjects with NAFLD showed metabolic syndrome, and 53% of subjects with metabolic syndrome had NAFLD. 4. The percentage of subjects who had more than two factors of metabolic syndrome was three times higher in the subjects with NAFLD compared to the controls. CONCLUSION: These results suggest that NAFLD may be independently related with insulin resistance. Metabolic diseases, such as glucose intolerance, obesity, dyslipidemia and hypertension, were more prevalent in the subjects with NAFLD than in the controls. Therefore, we should try to assess the status of the metabolic diseases, and treat them in patients with NAFLD.

Metabolic Abnormalities according to Severity of Non-alcoholic Fatty Liver Disease in Korean Adults.: H J Kim, D J Kim, S K Kim, S H Kim, Y M Rhee, C W Ahn, B S Cha, Y D Song, S K Lim, K R Kim, H C Lee, K B Huh; J Korean Endocr Soc. 2002;17(4):514-525. Published online August 1, 2002

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Abstract PDF: BACKGROUND
We evaluated the frequency of non-alcoholic fatty liver diseases, and the associations between the metabolic abnormalities and severity of non-alcoholic fatty liver disease in Korean adults using ultrasonography. METHODS: We examined 1074 Korean adults above the age of 30 years, comprising of 502 men and 572 women, participating in medical check-ups at the Health Promotion Center. Hepatitis B and C serologies were negative, and the average weekly alcohol intake was < or = 2 standard drinks. A standard interview, physical exam and biochemical study, were conducted, and an experienced operator carried out ultrasound liver studies. RESULTS: 522 of the subjects had non-alcoholic fatty liver disease, and the remaining 552 did not. The frequency in the men was higher than that in the women (57 vs 42%, p<0.05). The frequency of non-alcoholic fatty liver disease in the subjects without diabetes, obesity or dyslipidemia was 20%. We classified subjects into 4 groups: the controls (n=552) and those with mild (n=218), moderate (n=273) or severe fatty liver disease (n=31), according to their ultrasonographic findings. BMI, waist circumference, body fat, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, the total- to HDL-cholesterol ratio, impaired fasting glucose, hypertension and insulin resistance, were all significantly increased with the increased severity of non-alcoholic fatty liver disease (p<0.05). Following the multiple regression analyses, waist, alanine aminotransferase, HOMAIR, the total- to HDL-cholesterol ratio, aspartate aminotransferase and systolic blood pressure, were all associated with the severity of non-alcoholic fatty liver disease. Odd ratios of insulin resistance in the mild, moderate and severe non-alcoholic fatty liver disease were 14.7 (CI: 6.8~32.0), 6.9 (CI: 4.6~10.3) and 5.7 (CI3.6~8.8), respectively. The percentages of subjects with insulin resistance in each group were 7.6, 32.0, 36.0 and 55.0% (p<0.05), respectively. The percentages of subjects with risk of non-alcoholic steatohepatitis in each groups were 5.0, 21.6, 27.8 and 58.1% (p<0.05) respectively. CONCLUSION: The frequency of non-alcoholic fatty liver disease was relatively high in Korean adults. Proportional differences in metabolic abnormalities, relation to the severity of non-alcoholic fatty liver disease, were found by ultrasonography.

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