Endocrinology and Metabolism

Original Articles

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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Abstract PDF Supplementary Material PubReader ePub: 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.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Associations of Alcohol Consumption with All-Cause and Cancer Mortalities in Patients with Type 2 Diabetes Mellitus: A Nationwide Population Cohort Study: Da Yeon Lee, Sun-Joon Moon, Kyung-Do Han, Ji-Hee Ko, Han-na Jang, Hye-Mi Kwon, Se-Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2025;40(6):893-903. Published online July 14, 2025; DOI: https://doi.org/10.3803/EnM.2024.2275

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Background
To investigate the impact of alcohol consumption on all-cause and cancer mortalities in patients with type 2 diabetes (T2D).
Methods
This nationwide cohort study included Korean patients with T2D aged >20 years from a national health exams cohort (2009 to 2012). Participants were categorized based on alcohol consumption: non, mild (<30 g/day), and heavy drinkers (≥30 g/day). Primary outcomes were all-cause and cancer mortality rates. Cox proportional hazard regression analyses were used to calculate adjusted hazard ratios (aHRs) with a 95% confidence interval (CI) with adjustments for age, sex, body mass index, smoking, exercise, comorbidities, diabetes duration, and medications.
Results
Among 2,642,359 participants (median follow-up, 7.8 years), 57.2%, 32.7%, and 10.1% were non, mild, and heavy drinkers, respectively. Compared to non-drinkers, mild alcohol consumption was associated with reduced all-cause mortality (aHR, 0.81; 95% CI, 0.80 to 0.82) and cancer mortality (aHR, 0.88; 95% CI, 0.86 to 0.89), while heavy drinking increased both all-cause (aHR, 1.06; 95% CI, 1.04 to 1.07) and cancer mortalities (aHR, 1.09; 95% CI, 1.06 to 1.11). Subgroup analyses revealed variations: in chronic kidney disease and older age groups, heavy drinkers showed lower risk of all-cause mortality compared to non-drinkers. Regarding cancer mortality, younger and middle-aged groups showed protective effects of alcohol even for heavy drinkers, while females showed linear association between alcohol consumption and cancer mortality.
Conclusion
This study indicates a J-shaped relationship between alcohol consumption and all-cause and cancer mortality risk in patients with T2D, with variations across subgroups. These findings suggest the need for personalized recommendations considering individual risk factors.

Citations

Citations to this article as recorded by

Alcohol and the endocrine system: A critical review of disruptions, potential mechanisms, and health implications
Patricia E. Molina, Liz Simon
Alcohol, Clinical and Experimental Research.2026;[Epub] CrossRef
High BMI-attributable female-specific cancers: a comprehensive analysis of the global disease burden and trends from 1990 to 2021 and projections to 2040
Guangming Sun, Junmei Tang, Hao Chen, Yue Zhu, Pan Ren, Hanyue Gan, Wenbin Wu
Frontiers in Oncology.2025;[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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Abstract PDF Supplementary Material PubReader ePub: 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.

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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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
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
The Emerging Therapeutic Promise of SGLT2 Inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease
Wenjing Zhang, Huaidong Hu
Digestive Diseases and Sciences.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 Report

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

Review Article

Mineral, Bone & Muscle
Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia: Nobuaki Ito, Naoko Hidaka, Hajime Kato; Endocrinol Metab. 2024;39(2):255-261. Published online March 11, 2024; DOI: https://doi.org/10.3803/EnM.2023.1908

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Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning-Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.

Citations

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Surgical management strategies and clinical outcomes of cutaneous skeletal hypophosphatemia syndrome: a case series
Yi Qiao, Jin Dai, Ting Zhuang, Yicong Liu, Xiuzhi Ren
Frontiers in Pediatrics.2026;[Epub] CrossRef
Paraneoplastic endocrine syndromes: a contemporary overview
Juan Eduardo Quiroz-Aldave, Jacsel Suarez-Rojas, Elman Rolando Gamarra-Osorio, Katia Rivera-Fabián, María Del Carmen Durand-Vásquez, Luis Alberto Concepción-Urteaga, José Paz-Ibarra, Marcio José Concepción-Zavaleta
Expert Review of Endocrinology & Metabolism.2025; 20(1): 51. CrossRef
Excess fibroblast growth factor 23 in alcoholic osteomalacia is derived from the bone
Naoko Hidaka, Yuko Oyama, Minae Koga, Naoki Kondo, Yoichi Yasunaga, Taketoshi Shimakura, Noriaki Yamamoto, Hideaki E Takahashi, Yoichi Iwafuchi, So Watanabe, Soichiro Kimura, Yoshitomo Hoshino, Hajime Kato, Yuka Kinoshita, Hiroshi Kobayashi, Takeyuki Tana
JBMR Plus.2025;[Epub] CrossRef
X-linked hypophosphatemia and tumor-induced osteomalacia: a narrative review and expert opinion on the diagnostic and therapeutic challenges in the era of burosumab
Maria Luisa Brandi, Cristina Eller Vainicher, Danilo Fintini, Andrea Giusti, Andrea Magnolato, Salvatore Minisola, Sandro Giannini
Orphanet Journal of Rare Diseases.2025;[Epub] CrossRef
Acquired hypophosphatemic osteomalacia: case series from a Peruvian referral center (1999–2023)
José Paz-Ibarra, Sofía Sáenz-Bustamante, Manuel Inostroza-Fernández, Paola Sifuentes Hermenegildo, Liliana Ancajima Lescano, Marcio Concepción-Zavaleta, Alejandro Román-González, Alfredo Adolfo Reza-Albarrán
Archives of Osteoporosis.2024;[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
The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease
Rong Ren, Yanxia Pei, Lufei Kong, Yixin Shi
Journal of Diabetes and its Complications.2025; 39(2): 108932. CrossRef
Metabolic-Associated Steatotic Liver Disease (MASLD) and Type 2 Diabetes: Mechanisms, Diagnostic Approaches, and Therapeutic Interventions
Anastasia Ntikoudi, Anastasia Papachristou, Afroditi Tsalkitzi, Nikoletta Margari, Eleni Evangelou, Eugenia Vlachou
Diabetology.2025; 6(4): 23. CrossRef
DiabetesLiver score: A non-invasive algorithm for advanced liver fibrosis and liver-related outcomes in type 2 diabetes mellitus population
Chuan Liu, Jie Shen, Jie Li, Zhihui Li, Ming-Hua Zheng, Hua Bian, Xiqiao Zhou, Wenjing Ni, Zhongji Meng, Jiaojian Lv, Yijun Tang, Xuan Liang, Min Li, Taolong Zhou, Heng Wan, Yuping Chen, Yuxia Qi, Yuli Ge, Yan Wang, Wen-Yue Liu, Mingxing Huang, Shanghao L
Med.2025; 6(8): 100700. CrossRef
Multiple Definitions of Fatty Liver Disease: Which One Most Accurately Predicts Diabetes?
Eun-Jung Rhee
Endocrinology and Metabolism.2024; 39(2): 397. 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
Prevalence of High and Moderate Risk of Liver Fibrosis Among Patients With Diabetes at a Noncommunicable Diseases (NCD) Clinic in a Primary Healthcare Center in Northern India
Anubhav Mondal, Aninda Debnath, Ghurumourthy Dhandapani, Abhishek Sharma, Shveta Lukhmana, Geeta Yadav
Cureus.2023;[Epub] CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association among Current Smoking, Alcohol Consumption, Regular Exercise, and Lower Extremity Amputation in Patients with Diabetic Foot: Nationwide Population-Based Study: Yoon Jae Lee, Kyung-Do Han, Jun Hyeok Kim; Endocrinol Metab. 2022;37(5):770-780. Published online October 12, 2022; DOI: https://doi.org/10.3803/EnM.2022.1519

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Background
The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.
Methods
A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.
Results
The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.
Conclusion
Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

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Fatores associados à amputação de membros inferiores em pacientes diabéticos: uma abordagem epidemiológica
Edimar Chaves Junior, Ana Clara Paulino Queiroz, Arthur Felipe Vieira Bastos, Isadora Borges Toledo, Jessica Coelho Costa, Julien Barbosa, Lilian Nunes de Assis Lacerda, Marcos Bruno Couto Garcia, Maria Eduarda Avelina Bontempo, Maria Eduarda Mendes Reis,
Caderno Pedagógico.2025; 22(1): e13493. CrossRef
Are There Sex Differences in the Association of Alcohol Consumption With the Risk of Soft Tissue Sarcoma? A Nationwide Population-based Study in Korea
Min Wook Joo, Kyungdo Han, Yoon Joo Cho, Nicholas Matthew Bernthal, Ye Bin Park
Clinical Orthopaedics & Related Research.2025; 483(9): 1583. CrossRef
Knowledge, attitudes, and practices among patients with diabetic foot ulcers towards disease management
Liangxiao Xie, Changshun Wei, Liqun Chen, Huaqiang Zheng, Jiajia Dong, Jinzhi Wu
Scientific Reports.2025;[Epub] CrossRef
Diabetes‐Associated Major Limb Amputation in Solomon Islands: A National, 5‐Year Retrospective Study
Dylan M. Bush, Adrian Garcia Hernandez, Anita Pickard, Thomas H. Fitzpatrick, Rooney Jagilly, Micky Olangi, Michael Buin, Johanna Roth, Hendrick Kaniki, Jones Ghabu, Tony Quity, Alexandra L. Martiniuk
World Journal of Surgery.2025; 49(8): 2266. CrossRef
The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study
Jin Yu, Ji-Hyun Kim, Bongseong Kim, Kyungdo Han, Seung Hwan Lee, Mee Kyoung Kim
Endocrinology and Metabolism.2025; 40(4): 574. CrossRef
Nationwide study of income-based disparities in diabetic limb preservation in South Korea
Yoon Jae Lee, Kyung-Do Han, Jun Hyeok Kim
Scientific Reports.2025;[Epub] CrossRef
Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series
Rita de Cassia Ferreira, Rebeca Boltes Cecatto, Silvana Torres Perez, Raquel Agnelli Mesquita‐Ferrari, Sandra Kalil Bussadori, Cinthya Cosme Duran, Anna Carolina Tempestini Horliana, Kristianne Porta Santos Fernandes
Journal of Biophotonics.2024;[Epub] CrossRef
Factors associated with diabetic foot ulcers and lower limb amputations in type 1 and type 2 diabetes supported by real‐world data from the German/Austrian DPV registry
Alexander J. Eckert, Stefan Zimny, Marcus Altmeier, Ana Dugic, Anton Gillessen, Latife Bozkurt, Gabriele Götz, Wolfram Karges, Frank J. Wosch, Stephan Kress, Reinhard W. Holl
Journal of Diabetes.2024;[Epub] CrossRef
Patients with diabetic foot ulcers: A qualitative study of patient knowledge, experience, and encountered obstacles
Vahide Semerci Çakmak, Serap Çetinkaya Özdemir
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Gyuri Kim, Seohyun Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
BMC Medicine.2024;[Epub] CrossRef
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Magdalena Walicka, Arkadiusz Krysiński, Giusy Rita Maria La Rosa, Ang Sun, Davide Campagna, Agostino Di Ciaula, Tabinda Dugal, Andre Kengne, Phuong Le Dinh, Anoop Misra, Riccardo Polosa, Syed Abbas Raza, Cristina Russo, Roberta Sammut, Noel Somasundaram
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Visceral Adiposity as an Independent Risk Factor for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus: A Retrospective Study
Rui-Ling Wu, Niyao Chen, Yanni Chen, Xiaohong Wu, Chih-Yuan Ko, Xiao-Yu Chen, Takayuki Masaki
Journal of Diabetes Research.2024;[Epub] CrossRef
Age Characteristics of Patients With Type 2 Diabetic Foot Ulcers and Predictive Risk Factors for Lower Limb Amputation: A Population‐Based Retrospective Study
Yuanying Yao, Lei Chen, Yu Qian, Munmun Chattopadhyay
Journal of Diabetes Research.2024;[Epub] CrossRef
Investigating Diabetic Foot Pathophysiology and Amputation Prevention Strategies through Behavioral Modification
Jun Hyeok Kim
Journal of Wound Management and Research.2023; 19(3): 167. CrossRef

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.

Citations

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Growth Differentiation Factor 15 (GDF-15) as a modulator of hepatic steatosis and fibrosis: insights from a 6-year retrospective cohort study
Nicole Anna Dietzel, Maria Schmidt, Johannes Wiegand, Thomas Berg, Ronald Biemann, Ronny Baber, Michael Kluge, Kerstin Wirkner, Dirk Alexander Wittekind
Frontiers in Medicine.2026;[Epub] CrossRef
Appendicular skeletal muscle mass is associated with metabolic dysfunction-associated steatotic liver disease severity in young men: a cross-sectional and longitudinal study
Jaejun Lee, Jinson So, Chang In Han, Hyun Yang, Pil Soo Sung, Si Hyun Bae, Do Seon Song
Hepatology International.2025; 19(1): 181. CrossRef
Association between the triglyceride-glucose index and liver fibrosis in adults with metabolism-related fatty liver disease in the United States: a cross-sectional study of NHANES 2017–2020
Yuou Ying, Yuan Ji, Ruyi Ju, Jinhan Chen, Mingxian Chen
BMC Gastroenterology.2025;[Epub] 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
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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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Effect of Submaximal-Dose Semaglutide on MASLD Biopsy-Free Scoring Systems in Patients with Obesity
Boris Focko, Martin Jozef Péč, Zuzana Miertová, Jakub Jurica, Andrej Miert, Lucia Kubíková, Peter Tudík, Norbert Nagy, Patrik Lecký, Ivana Ságová, Tomáš Bolek, Daniel Ján Havaj, Ľubomír Skladaný, Marián Mokáň, Matej Samoš
Livers.2026; 6(1): 3. CrossRef
Glucagon-like peptide-1 and dual/triple receptor agonists in the treatment of metabolic dysfunction-associated steatotic liver disease: advances in mechanistic research
Xinyi Lu, Li Yang
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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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Therapeutic effects and mechanisms of Xinmaitong formula for type 2 diabetes mellitus via GLP-1R signaling
Weidong Pu, Yang Pan, Kang Yang, Jian Gao, Fen Tian, Jingrui Song, Yubing Huang, Yanmei Li
Frontiers in Pharmacology.2025;[Epub] CrossRef
Glucagon-like peptide-1 receptor agonists improve cholesterol metabolism by inhibiting SREBP-2 via SIRT6-AMPK pathway in HepG2 cells treated with palmitic acid
Jinmi Lee, Eun-Jung Rhee, Yu-Mi Lim, Seok-Woo Hong, Won-Young Lee
Cardiovascular Prevention and Pharmacotherapy.2025; 7(3): 61. CrossRef
Tirzepatide and Obesity: A Narrative Review
Arya Singh, Rahnuma Ahmad, Kona Chowdhury, Mahendra Narwaria, Mainul Haque
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GLP-1/GLP-1RAs: New Options for the Drug Treatment of NAFLD
Haoran Jiang, Linquan Zang
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Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan
Diabetes & Metabolism Journal.2024; 48(3): 354. CrossRef
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Inha Jung, Dae-Jeong Koo, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence
Salvatore Corrao, Chiara Pollicino, Dalila Maggio, Alessandra Torres, Christiano Argano
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Toshitaka Sawamura, Ren Mizoguchi, Ai Ohmori, Mitsuhiro Kometani, Takashi Yoneda, Shigehiro Karashima
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FABP1 induces lipogenesis by regulating the processing of SREBP1 in hepatocytes of large yellow croaker (Larimichthys crocea)
Fan Chen, Tingting Hao, Qiang Chen, Yuning Sun, Yanan Shen, Zengqi Zhao, Jianlong Du, Yueru Li, Kangsen Mai, Qinghui Ai
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Riccardo Nevola, Raffaella Epifani, Simona Imbriani, Giovanni Tortorella, Concetta Aprea, Raffaele Galiero, Luca Rinaldi, Raffaele Marfella, Ferdinando Carlo Sasso
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FAM3A mediates the phenotypic switch of human aortic smooth muscle cells stimulated with oxidised low-density lipoprotein by influencing the PI3K-AKT pathway
Lei Yang, Baoshun Du, Shitao Zhang, Maode Wang
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Jing Li, Han Yan, Rui Xiang, Weili Yang, Jingjing Ye, Ruili Yin, Jichun Yang, Yujing Chi
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Xiaohan Xu, Kyle L. Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang
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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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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
Scientific Reports.2025;[Epub] CrossRef
Body composition mediates the association between fatty acids and NAFLD risk: a prospective cohort study
Qishan Yang, Xinming Xu, Yue Chen, Zhicheng Zhang, Berty Ruping Song, Liang Sun, Xiang Gao
Journal of Health, Population and Nutrition.2025;[Epub] CrossRef
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
BMC Gastroenterology.2024;[Epub] CrossRef
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
Association between Alcohol Consumption and Metabolic Dysfunction-Associated Steatotic Liver Disease Based on Alcohol Flushing Response in Men: The Korea National Health and Nutrition Examination Survey 2019–2021
Dae Eon Kang, Si Nae Oh
Nutrients.2023; 15(18): 3901. CrossRef

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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Impact of Change, Fluctuation, or Variability in Weight on the Risk of Nonalcoholic Fatty Liver Disease in General Population: A Systematic Review and Meta‐Analysis
Dorsa Alijanzadeh, Masoud Noroozi, Negin Rostami, Narges Norouzkhani, Mahdie ShojaeiBaghini, Saeed Zivari Lashkajani, Ali Mirzaei, Maryam Dianati, Maryam Salimi, Hamidreza Sadeghsalehi, Faezeh Jadidian, Sajjad Ghane Ezabadi, Mohammad Sadegh Fallahi, Mobin
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Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model
Anouk Charlot, Anthony Bringolf, Léa Debrut, Joris Mallard, Anne-Laure Charles, Emilie Crouchet, Delphine Duteil, Bernard Geny, Joffrey Zoll
Nutrients.2024; 16(5): 646. CrossRef
Body weight variability and the risk of liver‐related outcomes in type 2 diabetes and steatotic liver disease: a cohort study
Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
Obesity.2024; 32(6): 1210. 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
A machine-learned model for predicting weight loss success using weight change features early in treatment
Farzad Shahabi, Samuel L. Battalio, Angela Fidler Pfammatter, Donald Hedeker, Bonnie Spring, Nabil Alshurafa
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Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish
Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang, Ching-Yi Chen
International Journal of Molecular Sciences.2024; 25(23): 13225. CrossRef
Weight variability, physical functioning and incident disability in older adults
Katie J. McMenamin, Tamara B. Harris, Joshua F. Baker
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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
Endocrinology and Metabolism.2022; 37(1): 74. 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
Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight
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.

Citations

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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
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.

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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
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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
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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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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
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Georgiana-Diana Cazac, Cristina-Mihaela Lăcătușu, Cătălina Mihai, Elena-Daniela Grigorescu, Alina Onofriescu, Bogdan-Mircea Mihai
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Review Article

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

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

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 Articles

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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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

Citations to this article as recorded by

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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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Abstract PDF PubReader ePub

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

Citations to this article as recorded by

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Review Articles

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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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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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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Thyroid
Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease: Wilmar M. Wiersinga; Endocrinol Metab. 2016;31(2):213-222. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.213

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Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

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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

Citations to this article as recorded by

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
Nonalcoholic Fatty Liver Disease Increases Cardiovascular Risk in Inflammatory Bowel Diseases
Dana Kablawi, Faisal Aljohani, Chiara Saroli Palumbo, Sophie Restellini, Alain Bitton, Gary Wild, Waqqas Afif, Peter L Lakatos, Talat Bessissow, Giada Sebastiani
Crohn's & Colitis 360.2023;[Epub] CrossRef
Low Relative Handgrip Strength Is Associated with a High Risk of Non-Alcoholic Fatty Liver Disease in Italian Adults: A Retrospective Cohort Study
Samantha Maurotti, Roberta Pujia, Elisa Mazza, Maria Francesca Pileggi, Franco Arturi, Maria Grazia Tarsitano, Tiziana Montalcini, Arturo Pujia, Yvelise Ferro
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Yedidya Saiman, Andres Duarte-Rojo, Mary E. Rinella
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Adriana Cervo, Giada Sebastiani, Jovana Milic, Thomas Krahn, Sergio Mazzola, Salvatore Petta, Antonio Cascio, Giovanni Guaraldi, Giovanni Mazzola
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Julia Karády, Maros Ferencik, Thomas Mayrhofer, Nandini M. Meyersohn, Daniel O. Bittner, Pedro V. Staziaki, Balint Szilveszter, Travis R. Hallett, Michael T. Lu, Stefan B. Puchner, Tracey G. Simon, Borek Foldyna, Geoffrey S. Ginsburg, Robert W. McGarrah,
Hepatology Communications.2022; 6(12): 3406. CrossRef
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Triglyceride Glucose Index Is Superior to the Homeostasis Model Assessment of Insulin Resistance for Predicting Nonalcoholic Fatty Liver Disease in Korean Adults
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Eun-Jung Rhee
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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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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.

Citations

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Do Vitamin D Levels Affect Bone Mineral Density in Reproductive Women with Low Ferritin Levels?
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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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Abstract PDF PubReader

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.

Citations

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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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Abstract PDF PubReader

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

Case Report

A Case of Fetal Alcohol Syndrome with Secondary Amenorrhea.: Yoon Young Cho, Hyo Jin Oh, Seok Jae Han, Sang Hun Sung, Gyu Hwan Bae, Ho Sang Shon, Hyun Dae Yoon; J Korean Endocr Soc. 2005;20(5):524-530. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.524

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Abstract PDF

Alcohol ingestion during pregnancy can be damaging to embryonic and fetal development. A specific pattern of malformation, identified as Fetal alcohol syndrome, has been documented in 1~2 of every 1,000 live infant births Fetal alcohol syndrome is characterized by growth deficiency, facial abnormalities, cardiac defects, minor joint and limb abnormalities, as well as central nervous system dysfunction, including microcephaly, mental retardation and abnormal neurobehavioral development. However, there are few reports of fetal alcohol syndrome associated with hormonal abnormality or amenorrhea. Recently, a case of secondary amenorrhea, which developed in a 19-year-old woman with fetal alcohol syndrome, was experienced at our institute, but the exact cause of the amenorrhea was difficulty to find. Herein, this case is reported, with a review of the literature.

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Citations to this article as recorded by

Alcohol Use during Pregnancy and Related Risk Factors in Korea
So Hee Lee, Seung Ju Shin, Seong-Du Won, Eun-Ju Kim, Dong-Yul Oh
Psychiatry Investigation.2010; 7(2): 86. CrossRef

Original Articles

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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