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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 21, 2024
DOI: https://doi.org/10.4093/dmj.2024.0541
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  • 136 Download
AbstractAbstract PDFPubReader   ePub   
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.
Original Articles
Guideline/Fact Sheet
2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Jaehyun Bae, Eonju Jeon, Ji Min Kim, Seon Mee Kang, Jung Hwan Park, Jae-Seung Yun, Bong-Soo Cha, Min Kyong Moon, Byung-Wan Lee
Diabetes Metab J. 2024;48(4):546-708.   Published online July 26, 2024
DOI: https://doi.org/10.4093/dmj.2024.0249
  • 5,957 View
  • 374 Download
  • 4 Crossref
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Citations

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  • Adherence to the nutritional recommendations according to diabetes status in Korean adults: a cross-sectional study
    Jong Han Choi, Chen Lulu, Seon-Joo Park, Hae-Jeung Lee
    BMC Public Health.2024;[Epub]     CrossRef
  • 당뇨병 치료의 진화: 관해를 향해가는 혁신적 약물치료와 첨단 관리기기의 결합
    종한 최, 민경 문
    Public Health Weekly Report.2024; 17(44): 1905.     CrossRef
  • The Impact of the Dietary Inflammatory Index, Fasting Blood Glucose, and Smoking Status on the Incidence and Survival of Pancreatic Cancer: A Retrospective Case–Control Study and a Prospective Study
    Ga Hyun Lee, Yeon Hee Kim, Sang Myung Woo, Woo Jin Lee, Sung-Sik Han, Sang-Jae Park, Sherry Price, Penias Tembo, James R. Hébert, Mi Kyung Kim
    Nutrients.2024; 16(22): 3941.     CrossRef
  • Enhancing Large Language Model Reliability: Minimizing Hallucinations with Dual Retrieval-Augmented Generation Based on the Latest Diabetes Guidelines
    Jaedong Lee, Hyosoung Cha, Yul Hwangbo, Wonjoong Cheon
    Journal of Personalized Medicine.2024; 14(12): 1131.     CrossRef
Drug/Regimen
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Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease
Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2022;46(5):701-712.   Published online June 3, 2022
DOI: https://doi.org/10.4093/dmj.2022.0002
  • 6,169 View
  • 352 Download
  • 13 Web of Science
  • 15 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).
Methods
Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.
Results
Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.
Conclusion
The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

Citations

Citations to this article as recorded by  
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    Kyoung Hwa Ha, Dae Jung Kim
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  • Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study
    Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim
    Endocrinology and Metabolism.2024; 39(5): 748.     CrossRef
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  • Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
    Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim
    Diabetes & Metabolism Journal.2024; 48(6): 1126.     CrossRef
  • Evaluating the appropriateness and the factors associated with sodium-glucose co-transporter 2 inhibitors prescribing in a Middle Eastern country: a cross-sectional study
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    International Journal of Clinical Pharmacy.2024;[Epub]     CrossRef
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    Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
    Journal of Diabetes Investigation.2024;[Epub]     CrossRef
  • Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis
    Teja Chakrala, Roshni O. Prakash, Justin Kim, Hanzhi Gao, Umar Ghaffar, Jaymin Patel, Alex Parker, Bhagwan Dass
    American Heart Journal Plus: Cardiology Research and Practice.2023; 28: 100286.     CrossRef
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    Seung-Hyun Ko
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    Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
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Review
Guideline/Fact Sheet
Article image
2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim, Sang Youl Rhee, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim, Chong Hwa Kim, Dae Jung Kim, SungWan Chun, Eun-Jung Rhee, Hyun Min Kim, Hyun Jung Kim, Donghyun Jee, Jae Hyun Kim, Won Seok Choi, Eun-Young Lee, Kun-Ho Yoon, Seung-Hyun Ko, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2021;45(4):461-481.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2021.0156
  • 29,808 View
  • 1,753 Download
  • 149 Web of Science
  • 165 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

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    Kyoung Hwa Ha, Kyung Ae Lee, Kyung-Do Han, Min Kyong Moon, Dae Jung Kim
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    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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  • The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-world Data Study
    Minyoung Kim, Hosu Kim, Kyong Young Kim, Soo Kyoung Kim, Junghwa Jung, Jong Ryeal Hahm, Jaehoon Jung, Jong Ha Baek
    Diabetes & Metabolism Journal.2023; 47(1): 135.     CrossRef
  • Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance
    Jun Sung Moon, Nam Hoon Kim, Jin Oh Na, Jae Hyoung Cho, In-Kyung Jeong, Soon Hee Lee, Ji-Oh Mok, Nan Hee Kim, Dong Jin Chung, Jinhong Cho, Dong Woo Lee, Sun Woo Lee, Kyu Chang Won
    Diabetes & Metabolism Journal.2023; 47(1): 82.     CrossRef
  • Evaluation and Management of Patients With Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
    Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
    International Journal of Heart Failure.2023; 5(1): 1.     CrossRef
  • Influenza vaccination trend and related factors among patients with diabetes in Korea: Analysis using a nationwide database
    Dong-Hwa Lee, Bumhee Yang, Seonhye Gu, Eung-Gook Kim, Youlim Kim, Hyung Koo Kang, Yeong Hun Choe, Hyun Jeong Jeon, Seungyong Park, Hyun Lee
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    Diabetes & Metabolism Journal.2023; 47(1): 42.     CrossRef
  • Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
    Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 10.     CrossRef
  • Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 1.     CrossRef
  • Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study
    Junghyun Noh, Min Kyong Moon, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
    Diabetes & Metabolism Journal.2023; 47(1): 59.     CrossRef
  • Analysis of the Incidence of Type 2 Diabetes, Requirement of Insulin Treatment, and Diabetes-Related Complications among Patients with Cancer
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    Cancers.2023; 15(4): 1094.     CrossRef
  • The 2022 focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension
    Hack-Lyoung Kim, Eun Mi Lee, Shin Young Ahn, Kwang-il Kim, Hyeon Chang Kim, Ju Han Kim, Hae-Young Lee, Jang Hoon Lee, Jong-Moo Park, Eun Joo Cho, Sungha Park, Jinho Shin, Young-Kwon Kim
    Clinical Hypertension.2023;[Epub]     CrossRef
  • Consistency of 1-day and 3-day average dietary intake and the relationship of dietary intake with blood glucose, hbA1c, BMI, and lipids in patients with type 2 diabetes
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    Journal of Korean Biological Nursing Science.2023; 25(1): 20.     CrossRef
  • 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
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  • Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension
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  • Association between antidiabetic drugs and the incidence of atrial fibrillation in patients with type 2 diabetes: A nationwide cohort study in South Korea
    Sunyoung Kim, So Young Park, Bongseong Kim, Chanyang Min, Wonyoung Cho, Dong Keon Yon, Joo Young Kim, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee, Sang Youl Rhee
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  • Effect of diabetes-specific oral nutritional supplements with allulose on weight and glycemic profiles in overweight or obese type 2 diabetic patients
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  • Associations Between Modifiable Risk Factors and Changes in Glycemic Status Among Individuals With Prediabetes
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  • Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: A 24‐week, multicentre, randomized, double‐blind, placebo‐controlled, phase III trial
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  • Adjusting the Use of Glucose-Lowering Agents in the Real-World Clinical Management of People with Type 2 Diabetes: A Narrative Review
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  • The association of perfluoroalkyl substances (PFAS) exposure and kidney function in Korean adolescents using data from Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018–2020): a cross-sectional study
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  • Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: Results of a 12‐week, multicentre, randomized, double‐blind, placebo‐controlled, phase 2 trial
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  • An Integrated Digital Health Care Platform for Diabetes Management With AI-Based Dietary Management: 48-Week Results From a Randomized Controlled Trial
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  • Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes
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  • Comparison of the effects of gemigliptin versus glimepiride on cardiac function in patients with type 2 diabetes uncontrolled with metformin: The gemi‐heart study
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  • Lost in translation: assessing the nomenclature change for diabetic kidney disease in Japan
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  • Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study
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  • Topic Modeling Analysis of Diabetes-Related Health Information during the Coronavirus Disease Pandemic
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  • Paradigm Shift in Management of Hyperglycemia in Patients with Type 2 Diabetes: Glucocentric versus Organ Protection
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  • Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes
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  • Association between the number of pregnancies and cardiac target organ damages: a cross-sectional analysis of data from the Korean women’s chest pain registry (KoROSE)
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    Journal of the Korean Medical Association.2023; 66(7): 427.     CrossRef
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    Journal of the Korean Medical Association.2023; 66(7): 421.     CrossRef
  • Identification of individuals at risk of hepatocellular carcinoma: screening for clinically significant liver fibrosis in patients with T2DM
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    Expert Review of Endocrinology & Metabolism.2023; 18(5): 355.     CrossRef
  • Additive impact of diabetes and sarcopenia on all-cause and cardiovascular mortality: A longitudinal nationwide population-based study
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    Metabolism.2023; 148: 155678.     CrossRef
  • Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis
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    Endocrinology and Metabolism.2023; 38(4): 426.     CrossRef
  • Incident infection risks depending on oral antidiabetic exposure in insulin-treated type 2 diabetes patients
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  • Dyslipidemia Fact Sheet in South Korea, 2022
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    Journal of Lipid and Atherosclerosis.2023; 12(3): 237.     CrossRef
  • Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020
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    Diabetes & Metabolism Journal.2023; 47(5): 643.     CrossRef
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  • Management of Dyslipidemia in Patients with Diabetes Mellitus
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    The Journal of Korean Diabetes.2023; 24(3): 111.     CrossRef
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Original Articles
Complications
Article image
Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus
Hae Kyung Kim, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
Diabetes Metab J. 2022;46(1):104-116.   Published online July 13, 2021
DOI: https://doi.org/10.4093/dmj.2020.0273
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

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Basic Research
Article image
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Diabetes Metab J. 2021;45(6):921-932.   Published online February 22, 2021
DOI: https://doi.org/10.4093/dmj.2020.0187
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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Technology/Device
Article image
Data Configuration and Publication Trends for the Korean National Health Insurance and Health Insurance Review & Assessment Database
Hae Kyung Kim, Sun Ok Song, Junghyun Noh, In-Kyung Jeong, Byung-Wan Lee
Diabetes Metab J. 2020;44(5):671-678.   Published online October 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0207
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AbstractAbstract PDFPubReader   ePub   
Background
Big data reports related to diseases and health care for the Korean population have been published since the National Health Insurance Service (NHIS) and the Health Insurance Review & Assessment (HIRA) Service provided limited open access to their databases. Here, we reviewed the structure, content, and means of using data from the National Health Insurance (NHI) system for the benefit of Korean researchers and presented the latest publication trends in Korean healthcare data procured from the NHI and HIRA databases.
Methods
Since 2013, researchers have been able to obtain nationwide population-based studies using the NHI and HIRA databases of the insured. We searched publications using the NHI and the HIRA databases between 2013 and 2019 retrieved from PubMed.
Results
The NHI and HIRA databases provide nationwide population-based data. The total number of publications from 2014 to 2019 using NHI and HIRA databases is 2,541 and 655, respectively. A total of 5,465 endocrinology-related studies were performed during 2014 to 2019.
Conclusion
The NHIS and HIRA databases have provided tools for guidelines to approach world-leading population-based epidemiology and disease research.

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Type 1 Diabetes
Article image
Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus
Jong Ha Baek, Woo Je Lee, Byung-Wan Lee, Soo Kyoung Kim, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Diabetes Metab J. 2021;45(1):46-54.   Published online July 10, 2020
DOI: https://doi.org/10.4093/dmj.2019.0134
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AbstractAbstract PDFPubReader   ePub   
Background

The aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).

Methods

A total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (<20, 20 to 29, and 30 to 40 years) according to age at diagnosis. Diabetic nephropathy (DN) was defined when spot urine-albumin creatinine ratio was 300 mg/g or more and/or estimated glomerular filtration ratio (eGFR) level was 60 mL/min/1.73 m2 or less.

Results

Median age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age <20 years) had lower stimulated C-peptide levels. They received more intensive insulin treatment with higher total daily insulin doses compared to older onset groups. The prevalence of DN was higher in the childhood/adolescent-onset group than in older onset groups (25.3% vs. 15.3% vs. 9.6%, P=0.022). The eGFR was inversely associated with disease duration whilst the degree of decrease was more prominent in the childhood/adolescent-onset group than in the later onset group (aged 30 to 40 years; P<0.001). Childhood/adolescent-onset group was independently associated with the risk of DN compared to the older onset group (aged 30 to 40 years; odds ratio, 3.47; 95% confidence interval, 1.45 to 8.33; P=0.005).

Conclusion

In individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.

Citations

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    Yen-Bo Lin, Wayne Huey-Herng Sheu, Su-Huey Lo, Yen-Po Yeh, Chien-Ning Huang, Chii-Min Hwu, Chang-Hsun Hsieh, Horng-Yi Ou, Lee-Ming Chuang, Jung-Fu Chen, Yu-Cheng Chen, Yun-Hsing Peng, Szu-Tah Chen, Shang-Ren Hsu, Yi-Ling Hsieh, Chih-Hsun Chu, Chieg-Hsiang
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Drug/Regimen
Article image
Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.   Published online May 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0203
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

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Review
Guideline/Fact Sheet
Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
Byung-Wan Lee, Yong-ho Lee, Cheol-Young Park, Eun-Jung Rhee, Won-Young Lee, Nan-Hee Kim, Kyung Mook Choi, Keun-Gyu Park, Yeon-Kyung Choi, Bong-Soo Cha, Dae Ho Lee, Korean Diabetes Association (KDA) Fatty Liver Research Group
Diabetes Metab J. 2020;44(3):382-401.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2020.0010
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AbstractAbstract PDFPubReader   

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

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Corrigendum
Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
Diabetes Metab J. 2019;43(5):731-731.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0188
Corrects: Diabetes Metab J 2019;43(1):31
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Citations

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Original Article
Clinical Diabetes & Therapeutics
Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea
Yu Mi Kang, Chang Hee Jung, Seung-Hwan Lee, Sang-Wook Kim, Kee-Ho Song, Sin Gon Kim, Jae Hyeon Kim, Young Min Cho, Tae Sun Park, Bon Jeong Ku, Gwanpyo Koh, Dol Mi Kim, Byung-Wan Lee, Joong-Yeol Park
Diabetes Metab J. 2019;43(4):432-446.   Published online June 19, 2019
DOI: https://doi.org/10.4093/dmj.2018.0092
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM).

Methods

This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia.

Results

The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011).

Conclusion

The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Citations

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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
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Short Communication
Clinical Diabetes & Therapeutics
A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor
You-Cheol Hwang, Jae Hyeon Kim, Byung-Wan Lee, Woo Je Lee
Diabetes Metab J. 2019;43(6):898-905.   Published online June 14, 2019
DOI: https://doi.org/10.4093/dmj.2018.0257
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AbstractAbstract PDFSupplementary MaterialPubReader   

We aimed to identify the clinical variables associated with a better glucose-lowering response to the sodium glucose cotransporter 2 inhibitor ipragliflozin in people with type 2 diabetes mellitus (T2DM). We especially focused on urinary glucose excretion (UGE). This was a single-arm multicenter prospective study. A total of 92 people with T2DM aged 20 to 70 years with glycosylated hemoglobin (HbA1c) levels ≥7.0% and ≤9.5% were enrolled. Ipragliflozin (50 mg) was added to the background therapy for these people for 12 weeks. After 3 months treatment with ipragliflozin, the mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of the people reached the HbA1c target of less than 7.0% (P<0.001). In addition, body weight, blood pressure, and lipid parameters were improved after ipragliflozin treatment (all P<0.001). The baseline HbA1c (r=0.66, P<0.001) and morning spot urine glucose to creatinine ratio (r=−0.30, P=0.001) were independently associated with the HbA1c reduction. Ipragliflozin treatment for 12 weeks improves glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicts a better glucose-lowering efficacy of ipragliflozin.

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Review
Clinical Diabetes & Therapeutics
Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment
Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
Diabetes Metab J. 2019;43(2):127-143.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2019.0034
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AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.

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Original Article
Metabolic Risk/Epidemiology
Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus
Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh
Diabetes Metab J. 2020;44(2):267-276.   Published online February 28, 2019
DOI: https://doi.org/10.4093/dmj.2019.0001
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AbstractAbstract PDFPubReader   
Background

Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods

We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results

LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions

Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

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  • Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
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