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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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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
Drug/Regimen
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Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park
Diabetes Metab J. 2024;48(3):418-428.   Published online February 2, 2024
DOI: https://doi.org/10.4093/dmj.2023.0030
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  • 2 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the real-world safety and effectiveness of dulaglutide in Korean adults with type 2 diabetes mellitus (T2DM).
Methods
This was a real-world, prospective, non-interventional post-marketing safety study conducted from May 26, 2015 to May 25, 2021 at 85 Korean healthcare centers using electronic case data. Data on patients using dulaglutide 0.75 mg/0.5 mL or the dulaglutide 1.5 mg/0.5 mL single-use pens were collected and pooled. The primary objective was to report the frequency and proportion of adverse and serious adverse events that occurred. The secondary objective was to monitor the effectiveness of dulaglutide at 12 and 24 weeks by evaluating changes in glycosylated hemoglobin (HbA1c ), fasting plasma glucose, and body weight.
Results
Data were collected from 3,067 subjects, and 3,022 subjects who received ≥1 dose (of any strength) of dulaglutide were included in the safety analysis set (53% female, mean age 56 years; diabetes duration 11.2 years, mean HbA1c 8.8%). The number of adverse events reported was 819; of these, 68 (8.3%) were serious adverse events. One death was reported. Adverse events were mostly mild in severity; 60.81% of adverse events were considered related to dulaglutide. This study was completed by 72.73% (2,198/3,022) of subjects. At 12/24 weeks there were significant (P<0.0001) reductions from baseline in least-squares mean HbA1c (0.96%/0.95%), fasting blood glucose (26.24/24.43 mg/dL), and body weight (0.75/1.21 kg).
Conclusion
Dulaglutide was generally well tolerated and effective in real-world Korean individuals with T2DM. The results from this study contribute to the body of evidence for dulaglutide use in this population.

Citations

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  • One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients
    Myung Jin Kim, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee
    Clinical Therapeutics.2024; 46(9): 683.     CrossRef
  • Safety and Effectiveness of Naltrexone-Bupropion in Korean Adults with Obesity: Post-Marketing Surveillance Study
    Young Lyu, Hongyup Ahn, Sangmo Hong, Cheol-Young Park
    Drug Design, Development and Therapy.2024; Volume 18: 5255.     CrossRef
Metabolic Risk/Epidemiology
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Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography
Hwi Seung Kim, Jiwoo Lee, Eun Hee Kim, Min Jung Lee, In Young Bae, Woo Je Lee, Joong-Yeol Park, Hong-Kyu Kim, Chang Hee Jung
Diabetes Metab J. 2023;47(1):104-117.   Published online January 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0081
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  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population.
Methods
Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores.
Results
According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all).
Conclusion
A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Citations

Citations to this article as recorded by  
  • Association between atherogenic dyslipidemia and muscle quality defined by myosteatosis
    Hwi Seung Kim, Yun Kyung Cho, Myung Jin Kim, Eun Hee Kim, Min Jung Lee, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Myosteatosis Predicts Bariatric Surgery Response: A Longitudinal Study in Patients With Morbid Obesity
    Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Artificial intelligence-based evaluation of prognosis in cirrhosis
    Yinping Zhai, Darong Hai, Li Zeng, Chenyan Lin, Xinru Tan, Zefei Mo, Qijia Tao, Wenhui Li, Xiaowei Xu, Qi Zhao, Jianwei Shuai, Jingye Pan
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Hwi Seung Kim, Hong-Kyu Kim, Chang Hee Jung
    Diabetes & Metabolism Journal.2023; 47(2): 304.     CrossRef
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Eun Roh
    Diabetes & Metabolism Journal.2023; 47(2): 301.     CrossRef
  • Sarcopenia, a condition shared by various diseases: can we alleviate or delay the progression?
    Giovanni Tarantino, Gaia Sinatti, Vincenzo Citro, Silvano Santini, Clara Balsano
    Internal and Emergency Medicine.2023; 18(7): 1887.     CrossRef
  • Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
    Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
    Clinical and Molecular Hepatology.2023; 29(4): 987.     CrossRef
  • Current view of the surgical anatomy of the anterolateral abdominal wall muscles and their aponeuroses
    A.V. Pavlov, A.S. Baranova, A.V. Fedoseyev, A.I. Vvedensky, G.S. Lazutina, N.V. Ovchinnikova, I.V. Bakharev
    Operativnaya khirurgiya i klinicheskaya anatomiya (Pirogovskii nauchnyi zhurnal).2023; 7(3): 44.     CrossRef
  • Muscle Fat Content Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Chinese Adults
    W. Guo, X. Zhao, D. Cheng, X. Liang, M. Miao, X. Li, J. Lu, N. Xu, Shuang Hu, Qun Zhang
    The Journal of nutrition, health and aging.2023; 27(11): 960.     CrossRef
Response
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Hwi Seung Kim, Woo Je Lee
Diabetes Metab J. 2022;46(4):665-666.   Published online July 27, 2022
DOI: https://doi.org/10.4093/dmj.2022.0166
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Citations

Citations to this article as recorded by  
  • Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide
    Maria Elena Lunati, Vincenzo Cimino, Davide Bernasconi, Alessandra Gandolfi, Paola Silvia Morpurgo, Camilla Tinari, Elisa Lazzaroni, Laura Baruffaldi, Milena Muratori, Laura Montefusco, Ida Pastore, Antonio Rossi, Ivano Giuseppe Franzetti, Fabrizio Murato
    Pharmacological Research.2024; 199: 107040.     CrossRef
Short Communication
Technology/Device
A 4-Week, Two-Center, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of EOPatch in Well-Controlled Type 1 Diabetes Mellitus
Jiyun Park, Nammi Park, Sangjin Han, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Woo Je Lee, Jae Hyeon Kim
Diabetes Metab J. 2022;46(6):941-947.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0299
  • 6,226 View
  • 299 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
This study evaluated the safety and efficacy of tubeless patch pump called EOPatch in patients with well-controlled type 1 diabetes mellitus (T1DM). This 4-week, two-center, open-label, single-arm study enrolled 10 adult patients diagnosed with T1DM with glycosylated hemoglobin less than 7.5%. The co-primary end points were patch pump usage time for one attachment and number of serious adverse events related to the patch pump. The secondary end points were total amount of insulin injected per patch and changes in glycemic parameters including continuous glucose monitoring data compared to those at study entry. The median usage time per patch was 84.00 hours (interquartile range, 64.50 to 92.50). Serious adverse events did not occur during the trial. Four weeks later, time in range 70 to 180 mg/dL was significantly improved (70.71%±17.14 % vs. 82.96%±9.14%, P=0.01). The times spent below range (<54 mg/dL) and above range (>180 mg/dL) also improved (All P<0.05). Four-week treatment with a tubeless patch pump was safe and led to clinical improvement in glycemic control.

Citations

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  • Multilayer track‐etched membrane‐based electroosmotic pump for drug delivery
    Qian Yang, Zebo Zhang, Junshu Lin, Boyu Zhu, Rongying Yu, Xinru Li, Bin Su, Bo Zhao
    ELECTROPHORESIS.2024; 45(5-6): 433.     CrossRef
  • Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial
    Ji Yoon Kim, Sang-Man Jin, Eun Seok Kang, Soo Heon Kwak, Yeoree Yang, Jee Hee Yoo, Jae Hyun Bae, Jun Sung Moon, Chang Hee Jung, Ji Cheol Bae, Sunghwan Suh, Sun Joon Moon, Sun Ok Song, Suk Chon, Jae Hyeon Kim
    Diabetologia.2024; 67(7): 1235.     CrossRef
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    Frontiers in Medicine.2024;[Epub]     CrossRef
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    Mohammad Towhidul Islam Rimon, Md Wasif Hasan, Mohammad Fuad Hassan, Sevki Cesmeci
    Pharmaceutics.2024; 16(7): 944.     CrossRef
  • A true continuous healthcare system for type 1 diabetes
    Jiyong Kim, Salman Khan, Eun Kyu Kim, Hye-Jun Kil, Bo Min Kang, Hyo Geon Lee, Jin-Woo Park, Jun Young Yoon, Woochul Kim
    Nano Energy.2023; 113: 108553.     CrossRef
Original Article
Metabolic Risk/Epidemiology
Article image
Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus
Eun Hee Kim, Hong-Kyu Kim, Min Jung Lee, Sung-Jin Bae, Jaewon Choe, Chang Hee Jung, Chul-Hee Kim, Joong-Yeol Park, Woo Je Lee
Diabetes Metab J. 2022;46(3):486-498.   Published online November 18, 2021
DOI: https://doi.org/10.4093/dmj.2021.0095
  • 13,159 View
  • 423 Download
  • 30 Web of Science
  • 36 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM).
Methods
A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline.
Results
During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm2 and 1.08 in men, respectively, and 85.7 cm2 and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively.
Conclusion
Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm2 or VSR ≥1.0 in men; VFA ≥85 cm2 or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

Citations

Citations to this article as recorded by  
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    Eric Robles Garibay, Sylvia M. Cruz, Sean J. Judge, Arta M. Monjazeb, Steven W. Thorpe, William J. Murphy, Jing Lyu, Shuai Chen, Cyrus P. Bateni, Robert J. Canter
    Journal of Surgical Oncology.2024; 130(3): 543.     CrossRef
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    Fan Yang, Weiliang Tian, Shikun Luo, Wuhan Li, Guoping Zhao, Risheng Zhao, Tao Tian, Yunzhao Zhao, Zheng Yao, Qian Huang
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    Christopher Seet, Laura Clementoni, Mohammed Rashid Akhtar, Pankaj Chandak, Mohammed Saoud, Amr Elsaadany, Muhammad Magdi Yaqoob, Ismail Heyder Mohamed, Muhammad Arslan Khurram
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    Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
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    Min-Kyung Lee, Jae-Hyuk Lee, Seo Young Sohn, Jiyeon Ahn, Oak-Kee Hong, Mee-Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon
    Diabetology & Metabolic Syndrome.2023;[Epub]     CrossRef
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  • Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
    Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
    Clinical and Molecular Hepatology.2023; 29(4): 987.     CrossRef
  • Visceral adipose tissue reference data computed for GE HealthCare DXA from the National Health and Nutrition Examination Survey data set
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  • Comparison of bioelectrical body and visceral fat indices and anthropometric measures in relation to type 2 diabetes by sex among Chinese adults, a cross-sectional study
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    Frontiers in Public Health.2023;[Epub]     CrossRef
  • The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics
    Jiajun Qiu, Maobin Kuang, Yang Zou, Ruijuan Yang, Qing Shangguan, Dingyang Liu, Guotai Sheng, Wei Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy
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    Cardiovascular Research.2022;[Epub]     CrossRef
  • Implication of Sex Differences in Visceral Fat for the Assessment of Incidence Risk of Type 2 Diabetes Mellitus
    Sang Hyeon Ju, Hyon-Seung Yi
    Diabetes & Metabolism Journal.2022; 46(3): 414.     CrossRef
  • Visceral fat area and body fat percentage measured by bioelectrical impedance analysis correlate with glycometabolism
    Shuying Li, Shaoping Li, Jie Ding, Weihong Zhou
    BMC Endocrine Disorders.2022;[Epub]     CrossRef
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    Furong Xu, Jacob E. Earp, Bryan J. Blissmer, Ingrid E. Lofgren, Matthew J. Delmonico, Geoffrey W. Greene
    International Journal of Environmental Research and Public Health.2022; 19(19): 12103.     CrossRef
  • Visceral Obesity Is a More Important Factor for Colorectal Adenomas than Skeletal Muscle or Body Fat
    Ji Yeon Seo, Yoo Min Han, Su Jin Chung, Seon Hee Lim, Jung Ho Bae, Goh Eun Chung
    Cancers.2022; 14(21): 5256.     CrossRef
  • Recent Advances in Visceral Obesity and Related Diseases
    佳佳 魏
    Advances in Clinical Medicine.2022; 12(12): 11686.     CrossRef
  • Gender differences in the ideal cutoffs of visceral fat area for predicting MAFLD in China
    Pingping Yu, Huachao Yang, Xiaoya Qi, Ruixue Bai, Shouqin Zhang, Jianping Gong, Ying Mei, Peng Hu
    Lipids in Health and Disease.2022;[Epub]     CrossRef
Short Communications
Drug/Regimen
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study
Hwi Seung Kim, Taekwan Yoon, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee
Diabetes Metab J. 2022;46(4):658-662.   Published online November 8, 2021
DOI: https://doi.org/10.4093/dmj.2021.0232
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Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m2, and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was −2.8 kg (95% CI, −4.21 to −1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

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    Aftab Ahmad, Hani Sabbour
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    Hwi Seung Kim, Woo Je Lee
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Drug/Regimen
Article image
Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review
Hwi Seung Kim, Jiwoo Lee, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee
Diabetes Metab J. 2021;45(6):948-953.   Published online February 5, 2021
DOI: https://doi.org/10.4093/dmj.2020.0180
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

Citations

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Original Articles
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.

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    Ye Seul Yang, Tae Seo Sohn
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Cardiovascular Risk/Epidemiology
Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry
Gyung-Min Park, Chang Hoon Lee, Seung-Whan Lee, Sung-Cheol Yun, Young-Hak Kim, Yong-Giun Kim, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dong Hyun Yang, Joon-Won Kang, Tae-Hwan Lim, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Hong-Kyu Kim, Jaewon Choe, Sang-Gon Lee
Diabetes Metab J. 2020;44(3):470-479.   Published online November 22, 2019
DOI: https://doi.org/10.4093/dmj.2019.0073
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.

Methods

We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively.

Results

Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; P=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; P=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; P<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; P<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (P=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (P=0.023).

Conclusion

Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

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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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Original Article
Clinical Diabetes & Therapeutics
Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials
Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong-Yeol Park, Ye-Jee Kim, Chang Hee Jung, Michael A. Nauck
Diabetes Metab J. 2019;43(4):410-421.   Published online December 27, 2018
DOI: https://doi.org/10.4093/dmj.2018.0070
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.

Methods

Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.

Results

Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001).

Conclusion

Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.

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Reviews
Pathophysiology
Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance
Yu Mi Kang, Francis Kim, Woo Je Lee
Diabetes Metab J. 2017;41(2):89-95.   Published online November 15, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.2.89
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AbstractAbstract PDFPubReader   

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

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Clinical Care/Education
Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Diabetes Metab J. 2016;40(5):339-353.   Published online September 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.339
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AbstractAbstract PDFPubReader   

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor. Various studies have shown that gemigliptin is an optimized DPP-4 inhibitor in terms of efficacy, safety, and patient compliance for treatment of type 2 diabetes mellitus. In this review, we summarize the characteristics of gemigliptin and discuss its potential benefits in clinical practice.

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Original Article
Complications
Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis
Jaechan Leem, Eun Hee Koh, Jung Eun Jang, Chang-Yun Woo, Jin Sun Oh, Min Jung Lee, Joon-Won Kang, Tae-Hwan Lim, Chang Hee Jung, Woo Je Lee, Joong-Yeol Park, Ki-Up Lee
Diabetes Metab J. 2015;39(5):414-423.   Published online October 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.5.414
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AbstractAbstract PDFPubReader   
Background

The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD.

Methods

We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery.

Results

Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028).

Conclusion

Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.

Citations

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