Diabetes & Metabolism Journal

Review

Guideline/Statement/Fact Sheet
Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications: Jae Hyun Bae, Hun Jee Choe, Ye Seul Yang, Mi Hae Seo, Jong Han Choi, Gyuri Kim, Young Sang Lyu, Jeung Hun Han, Shinae Kang, Won Jun Kim, Kyung-Soo Kim, Young Min Cho, Bong Soo Cha, for the Severe Diabetes Mellitus Task Force of the Korean Diabetes Association; Diabetes Metab J. 2025;49(6):1141-1154. Published online October 28, 2025; DOI: https://doi.org/10.4093/dmj.2025.0739

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Diabetes mellitus comprises a heterogeneous group of metabolic disorders differing in etiology, clinical course, and outcomes. Traditional classifications, such as type 1 and type 2 diabetes mellitus, fail to capture the full heterogeneity, including variation in insulin deficiency, insulin resistance, and complication burden. To address these limitations, we propose the Diabetes Grade–Stage Classification, an integrated system that combines pathophysiology-based grading with complication-based staging. Grading quantifies metabolic dysfunction through the assessment of insulin deficiency and insulin resistance. In parallel, staging assesses the extent of target organ damage, particularly in the cardiovascular, renal, ocular, and nervous systems. Together, this framework enables a comprehensive assessment of disease status, identification of vulnerable or high-risk phenotypes, and implementation of risk-adapted management strategies. Clinically, it facilitates personalized care, promotes collaborative coordination, and strengthens physician–patient communication. Furthermore, this framework provides a scalable structure for integrating disease severity into both individual- and population-level interventions. Although the current criteria for grading and staging are based on expert consensus and selected clinical indicators, such as low C-peptide levels and advanced complications, further validation and refinement are needed. In conclusion, the grading and staging system provides an operational tool for classifying the severity of diabetes mellitus and has the potential to extend life expectancy and improve quality of life for people living with diabetes mellitus.

Citations

Citations to this article as recorded by

Material-driven glucose responsiveness in insulin delivery systems: carrier selection and performance
Zhihan Li, Jingge Jiang, Ziyu Zhu, Cheng Luo, Chunyi Xu, Chuanpin Chen, Guoqin Ren, Ruofei Huang, Dongjuan He
Frontiers in Endocrinology.2026;[Epub] CrossRef
Bridging Evidence and Practice: A Consensus Statement from the Korean Diabetes Association on Diabetes Screening, Pharmacological Treatment and Severe Diabetes
Jong Han Choi, Shinae Kang, Soo-Kyung Kim, Won Jun Kim, Ji Min Kim, Jaehyun Bae, Jae-Seung Yun, Eonju Jeon, Young-Eun Kim, Jae Hyun Bae, Hun Jee Choe, Young Min Cho, Seung-Hyun Ko, Sang Yong Kim, Hae Jin Kim, You-Cheol Hwang, Min Kyong Moon, Suk Chon, Seo
Diabetes & Metabolism Journal.2025; 49(6): 1155. CrossRef

Editorial

Addressing the Persistent Increase and Inequities in Metabolically Unhealthy Obesity: Toward an Understanding of Clinical Obesity: Young Sang Lyu, Sang Yong Kim; Diabetes Metab J. 2025;49(3):405-406. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0306

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Review

Guideline/Fact Sheet
Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association: Jaehyun Bae, Eugene Han, Hye Won Lee, Cheol-Young Park, Choon Hee Chung, Dae Ho Lee, Eun-Hee Cho, Eun-Jung Rhee, Ji Hee Yu, Ji Hyun Park, Ji-Cheol Bae, Jung Hwan Park, Kyung Mook Choi, Kyung-Soo Kim, Mi Hae Seo, Minyoung Lee, Nan-Hee Kim, So Hun Kim, Won-Young Lee, Woo Je Lee, Yeon-Kyung Choi, Yong-ho Lee, You-Cheol Hwang, Young Sang Lyu, Byung-Wan Lee, Bong-Soo Cha, on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association; Diabetes Metab J. 2024;48(6):1015-1028. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0541

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Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist’s perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.

Citations

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Comparison of diagnostic criteria for fatty liver disease in assessing cardiac dysfunction: a cross-sectional study
Yun Kyung Cho, Myung Jin Kim, Eun Hee Kim, Min Jung Lee, Hyo-Jung Nam, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
Hepatology International.2026; 20(1): 81. CrossRef
Biological determinants and outcomes of sex discrepancies in MASLD
Amedeo Lonardo, Mohamad Jamalinia, Ralf Weiskirchen
Metabolism and Target Organ Damage.2026;[Epub] CrossRef
Mazdutide Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Endoplasmic Reticulum Stress, Improving Lipid Metabolism and Alleviating Inflammation
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Special Population
Janus P. Ong, Hasmik Ghazinyan, Vincent Wai-Sun Wong, Yuichiro Eguchi
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Managing Metabolic Dysfunction–Associated Steatotic Liver Disease: Protocol for a Scoping Review of Patient Perceptions, Barriers, and Facilitators
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JMIR Research Protocols.2026; 15: e81404. CrossRef
Association between the Zhejiang University index and metabolic dysfunction-associated fatty liver disease as analyzed in National Health and Nutrition Examination Survey: A retrospective observational study
Wei Fu, Xiaoyue Wu, Guobin Cheng, Linya Lyu, Hulin Wang
Journal of International Medical Research.2026;[Epub] CrossRef
Aqueous Extract of Siraitia grosvenorii Alleviates MAFLD by Modulating Metabolism and Maintaining Gut Homeostasis in High-Fat Diet Fed Mice
Hong Li, Zhongzhen Zhao, Yiming Ding, Weixian Shao, Yu Zhou, Junxiu Li, Zailin Liang, Bin Peng, Fusheng Mo, Jiao Zheng, Shengli Wei, Yuan Zhang
Foods.2026; 15(7): 1241. CrossRef
Associations of body roundness index with steatotic liver disease and mortality from the UK biobank cohort study
Jinyoung Shin, Seok-Jae Heo, Yae-Ji Lee, Yu-Jin Kwon, Ji-Won Lee
BMC Gastroenterology.2026;[Epub] CrossRef
Income Persistence and the Risk of Hepatocellular Carcinoma in Individuals with Type 2 Diabetes
Jong-Ha Baek, Yong-Moon Mark Park, Benjamin C. Amick, Mario Schootman, Michael R. Thomsen, Oak-Kee Hong, Seung-Hyun Ko, Clare C. Brown, Marie-Rachelle Narcisse, Pearl A. McElfish, Seong-Su Lee, Kyungdo Han
Cancer Epidemiology, Biomarkers & Prevention.2026; 35(5): 743. CrossRef
Current Trends and Perspectives on Obesity and Metabolic Dysfunction-Associated Steatohepatitis in East Asia
Soo Lim, Hui Zhou, Wataru Ogawa
Journal of Obesity & Metabolic Syndrome.2026; 35(2): 130. CrossRef
DN203316, a novel PPARδ agonist, suppresses ferroptotic signaling and fibrogenesis in metabolic dysfunction-associated steatohepatitis
Ye Jin Kim, Jina Kim, Da Young An, Mihyang Park, Gui-Hwa Jeong, Jonghwa Jin, Mi Kyung Kim, Jungwook Chin, Yeon-Kyung Choi, Keun-Gyu Park
Experimental & Molecular Medicine.2026; 58(6): 1900. CrossRef
Association between the triglyceride-glycated hemoglobin index and diabetes risk among patients with Non-alcoholic fatty liver disease: A longitudinal cohort study
Cuimei Wei, Changchun Cao, Zengxin Xu, Gang Chen, Wenjing Liu, Miao Zhang, Haofei Hu, Shanghua Xu, Aleksandra Klisic
PLOS One.2026; 21(6): e0350633. CrossRef
Bioelectrical impedance analysis parameters are superior to liver enzymes in predicting metabolic dysfunction-associated steatotic liver disease in young adults
Kyungchul Song, Yu-Jin Kwon, Eunju Lee, Hye Sun Lee, Young Hoon Youn, Su Jung Baik, Hana Lee, Joon Young Kim, Youngha Choi, Hyun Wook Chae
Internal and Emergency Medicine.2025; 20(3): 785. CrossRef
Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease
Joonyub Lee, Won Gun Choi, Marie Rhee, Seung-Hwan Lee
Diabetes & Metabolism Journal.2025; 49(3): 348. CrossRef
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application
Jae Hyun Bae
Diabetes & Metabolism Journal.2025; 49(3): 386. CrossRef
Association of temporal MASLD with type 2 diabetes, cardiovascular disease and mortality
Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park
Cardiovascular Diabetology.2025;[Epub] CrossRef
Development of a simple metabolic score to predict liver fibrosis risk in chronic hepatitis B patients: A retrospective cross-sectional study
Li Liu, Peng Ye, Qiuping Gu, Ling Zeng, Lijuan Liang, Yingfeng Wei
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2025 Clinical Practice Guidelines for Diabetes: Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
Jaehyun Bae
The Journal of Korean Diabetes.2025; 26(3): 172. CrossRef
Research trends on the quality of life in patients with metabolic dysfunction-associated fatty liver diseases: a scientific metrology study
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Original Article

Drug/Regimen
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study: Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon; Diabetes Metab J. 2021;45(5):675-683. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0107

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Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

Citations to this article as recorded by

Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2026; 28(4): 3305. CrossRef
Empagliflozin-based quadruple oral therapy for type 2 diabetes: a prospective cohort study
Fatemeh Moosaie, Shiva Abedinzadeh, Soghra Rabizadeh, Kimia Daneshvar, Mohammadamin Noorafrooz, Fatemeh Alsadat Mojtahedi, Niloofar Deravi, Seyede Marzie Fatemi Abhari, Akam Ramezani, Alipasha Meysamie, Marzieh Hajibabaei, Sahar Karimpour Reyhan, Mahsa Ab
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Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
Rita Oliveira, Matilde Monteiro-Soares, José Pedro Guerreiro, Rúben Pereira, António Teixeira-Rodrigues
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Disease burden and symptom management in type 2 diabetic patients: A phenomenological study
Sevgi Demir Çam, Sevda Uzun
Public Health Nursing.2024; 41(6): 1291. CrossRef
Comparing dual oral agents plus insulin vs. Triple oral agents in uncontrolled type II diabetes: A pilot study
Nadia Gul, Inayat Ur Rehman, Yasar shah, Arbab Muhammad Ali, Zahid Ali, Omer Shehzad, Khang Wen Goh, Long Chiau Ming, Amal K. Suleiman, Nimesh Lageju
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Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
Kyung-Soo Kim, Kyung Ah Han, Tae Nyun Kim, Cheol-Young Park, Jung Hwan Park, Sang Yong Kim, Yong Hyun Kim, Kee Ho Song, Eun Seok Kang, Chul Sik Kim, Gwanpyo Koh, Jun Goo Kang, Mi Kyung Kim, Ji Min Han, Nan Hee Kim, Ji Oh Mok, Jae Hyuk Lee, Soo Lim, Sang S
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Effectiveness and safety of teneligliptin added to patients with type 2 diabetes inadequately controlled by oral triple combination therapy: A multicentre, randomized, double‐blind, and placebo‐controlled study
Minyoung Lee, Woo‐je Lee, Jae Hyeon Kim, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2022; 24(6): 1105. CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
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Glycaemic control with add‐on thiazolidinedione or a sodium‐glucose co‐transporter‐2 inhibitor in patients with type 2 diabetes after the failure of an oral triple antidiabetic regimen: A 24‐week, randomized controlled trial
Jaehyun Bae, Ji Hye Huh, Minyoung Lee, Yong‐Ho Lee, Byung‐Wan Lee
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