- Metabolic Risk/Epidemiology
- Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study
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Ji-Hee Sung, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
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Diabetes Metab J. 2024;48(6):1105-1113. Published online August 19, 2024
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DOI: https://doi.org/10.4093/dmj.2023.0444
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Abstract
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- Background
We investigated the association between uterine leiomyoma (UL) and incident type 2 diabetes mellitus (T2DM) in young women.
Methods A nationwide population-based cohort study of 2,541,550 women aged between 20 and 40 years was performed using the National Health Information Database. Cox proportional hazards models were used to analyze the risk of incident T2DM according to the presence of UL and myomectomy.
Results The mean age was 29.70 years, and mean body mass index was 21.31 kg/m2. Among 2,541,550 participants, 18,375 (0.72%) women had UL. During a median 7.45 years of follow-up, 23,829 women (0.94%) were diagnosed with T2DM. The incidence of T2DM in women with UL (1.805/1,000 person-years) was higher than in those without UL (1.289/1,000 person-years). Compared with women without UL, women with UL had a higher risk of incident T2DM (hazard ratio, 1.216; 95% confidence interval [CI], 1.071 to 1.382). Women with UL who did not undergo myomectomy had a 1.505 times (95% CI, 1.297 to 1.748) higher risk for incident T2DM than women without UL. However, women with UL who underwent myomectomy did not have increased risk for incident T2DM.
Conclusion Young women with UL were associated with a high risk of incident T2DM. In addition, myomectomy seemed to attenuate the risk for incident T2DM in young women with UL.
- 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
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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
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Diabetes Metab J. 2024;48(6):1015-1028. Published online November 21, 2024
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DOI: https://doi.org/10.4093/dmj.2024.0541
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Abstract
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.
- Drug/Regimen
- Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
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Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee
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Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024
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DOI: https://doi.org/10.4093/dmj.2023.0077
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Abstract
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- Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
- Guideline/Fact Sheet
- Fatty Liver & Diabetes Statistics in Korea: Nationwide Data 2009 to 2017
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Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park, on Behalf of Fatty Liver Research Group of the Korean Diabetes Association
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Diabetes Metab J. 2023;47(3):347-355. Published online March 29, 2023
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DOI: https://doi.org/10.4093/dmj.2022.0444
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Abstract
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- Background
This study investigated the changes of fatty liver disease prevalence in general Korean population.
Methods This study analyzed data from the Korean National Health Insurance Service from 2009 to 2017 that included individuals aged 20 years or older who had undergone a medical health examination. Fatty liver disease was assessed using the fatty liver index (FLI). The disease severity was defined by FLI cutoff, ≥30 as moderate, and ≥60 as severe fatty liver disease.
Results The prevalence of Korean adults aged 20 years or over with fatty liver disease (FLI ≥60) increased from 13.3% in 2009 to 15.5% in 2017 (P for trend <0.001). The increase in fatty liver disease prevalence was prominent in men (from 20.5% to 24.2%) and the young age (20 to 39 years) group (from 12.8% to 16.4%) (P for interaction <0.001). The prevalence of fatty liver disease was the highest in type 2 diabetes mellitus (T2DM, 29.6%) population compared to that of prediabetes or normoglycemia (10.0% and 21.8%) in 2017. The prevalence of fatty liver disease had statistically increased in individuals with T2DM and prediabetes (P for trend <0.001). Its prevalence increased more steeply in the young-aged population with T2DM, from 42.2% in 2009 to 60.1% in 2017. When applying a lower FLI cutoff (≥30) similar results were observed.
Conclusion The prevalence of fatty liver disease in the Korean population has increased. Individuals who are young, male, and have T2DM are vulnerable to fatty liver disease.
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Citations
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- Longitudinal changes in fatty liver index are associated with risk of hepatocellular carcinoma: A nationwide cohort study in Korea
Min Gu Kang, Chang Hun Lee, Chen Shen, Jong Seung Kim, Ji Hyun Park Journal of Hepatology.2024; 80(5): e216. CrossRef - Repeated detection of non‐alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults
Jin Hwa Kim, Young Sang Lyu, Mee Kyoung Kim, Sang Yong Kim, Ki‐Hyun Baek, Ki‐Ho Song, Kyungdo Han, Hyuk‐Sang Kwon Diabetes, Obesity and Metabolism.2024; 26(1): 180. CrossRef - Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-ho Lee, Seung Up Kim Metabolism.2024; 152: 155789. CrossRef - Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park BMJ.2024; : e076388. CrossRef - Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome
Scott L. Friedman Diabetes & Metabolism Journal.2024; 48(2): 161. CrossRef - Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective
Inha Jung, Dae-Jeong Koo, Won-Young Lee Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef - Association between long working hours and metabolic dysfunction–associated steatotic liver disease: a nationwide population-based study in Korea
S.-U. Baek, J.-U. Won, Y.-M. Lee, J.-H. Yoon Public Health.2024; 232: 188. CrossRef - Association between Dietary Quality and Non-Alcoholic Fatty Liver Disease in Korean Adults: A Nationwide, Population-Based Study Using the Korean Healthy Eating Index (2013–2021)
Seong-Uk Baek, Taeyeon Kim, Yu-Min Lee, Jong-Uk Won, Jin-Ha Yoon Nutrients.2024; 16(10): 1516. CrossRef - Liver Cancer Risk Across Metabolic Dysfunction-Associated Steatotic Liver Disease and/or Alcohol: A Nationwide Study
Byungyoon Yun, Heejoo Park, Sang Hoon Ahn, Juyeon Oh, Beom Kyung Kim, Jin-Ha Yoon American Journal of Gastroenterology.2024;[Epub] CrossRef - Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated with Increased Risk of Kidney Cancer: A Nationwide Study
Juyeon Oh, Beom Kyung Kim, Jin-Ha Yoon, Hyung Ho Lee, Heejoo Park, Jian Lee, Youngsun Park, Byungyoon Yun, Jinsoo Chung Cancers.2024; 16(18): 3161. CrossRef - 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- Diabetes & Metabolism Journal.2024; 48(6): 1015. CrossRef - High-Sensitivity C-Reactive Protein Levels in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Alcohol-Associated Liver Disease (MetALD), and Alcoholic Liver Disease (ALD) with Metabolic Dysfunction
Seong-Uk Baek, Jin-Ha Yoon Biomolecules.2024; 14(11): 1468. CrossRef - Reply to G. Wang et al
Joo-Hyun Park, Jung Yong Hong, Kyungdo Han Journal of Clinical Oncology.2023; 41(32): 5070. CrossRef - The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review
Teodora Biciusca, Sorina Ionelia Stan, Mara Amalia Balteanu, Ramona Cioboata, Alice Elena Ghenea, Suzana Danoiu, Ana-Maria Bumbea, Viorel Biciusca Diagnostics.2023; 13(21): 3316. CrossRef - Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?
Eugene Han, Yong-ho Lee Clinical and Molecular Hepatology.2023; 29(4): 980. CrossRef - Approach to Fatty Liver Disease in Patients with Type 2 Diabetes
Ji Cheol Bae The Journal of Korean Diabetes.2023; 24(3): 107. CrossRef
- Metabolic Risk/Epidemiology
- Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
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Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Diabetes Metab J. 2023;47(2):220-231. Published online January 12, 2023
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DOI: https://doi.org/10.4093/dmj.2021.0327
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
We investigated whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with an elevated risk of all-cause and cardiovascular mortality using a large-scale health examination cohort.
Methods A total of 394,835 subjects in the Kangbuk Samsung Health Study cohort were enrolled from 2002 to 2012. Participants were categorized by the presence of nonalcoholic fatty liver disease (NAFLD) and MAFLD as follows: normal subjects; patients with both NAFLD and MAFLD; patients with NAFLD only; and patients with MAFLD only. Cox proportional hazards models were used to analyze the risk of mortality.
Results During a median 5.7 years of follow-up, 20.69% was patients with both NAFLD and MAFLD, 1.51% was patients with NAFLD only, and 4.29% was patients with MAFLD only. All-cause and cardiovascular death was higher in patients with MAFLD than those without MAFLD (P<0.001, respectively). In patients with MAFLD only, the hazard ratio (HR) of all-cause and cardiovascular death was 1.35 (95% confidence interval [CI], 1.13 to 1.60) and 1.90 (95% CI, 1.26 to 2.88) after adjusting for age, which lost its statistical significance by multivariable adjustments. Compared to patients with less than two components of metabolic dysfunction, patients with more than two components of metabolic dysfunction were a higher risk of cardiovascular death (HR, 2.05; 95% CI, 1.25 to 3.38) and only women with more than two components of metabolic dysfunction were a higher risk of all-cause death (HR, 1.44; 95% CI, 1.02 to 2.03).
Conclusion MAFLD criteria could identify a high-risk group for all-cause and cardiovascular death.
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Citations
Citations to this article as recorded by
- Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-ho Lee, Seung Up Kim Metabolism.2024; 152: 155789. CrossRef - Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park BMJ.2024; : e076388. CrossRef - Sex differences in mortality and liver‐related events in non‐alcoholic fatty liver disease: A systematic review and meta‐analysis
Huimin Zhou, Haiyan Chen, Hanxiao Lu, Bo Wu, Shuo Zhang, Yuanlong Gu, Guangwen Zhou, Jie Xiang, Jun Yang Liver International.2024; 44(7): 1600. CrossRef - Association between dietary carbohydrate to fiber ratio and metabolic dysfunction associated fatty liver disease in adults: evidence from the NHANES 2017–2020
Zhenmin Liu, Taiyong Fang Journal of Health, Population and Nutrition.2024;[Epub] CrossRef - NAFLD and MAFLD independently increase the risk of major adverse cardiovascular events (MACE): a 20-year longitudinal follow-up study from regional Australia
Karl Vaz, William Kemp, Ammar Majeed, John Lubel, Dianna J. Magliano, Kristen M. Glenister, Lisa Bourke, David Simmons, Stuart K. Roberts Hepatology International.2024; 18(4): 1135. CrossRef - Clinical outcomes of MAFLD versus NAFLD: A meta‐analysis of observational studies
Grazia Pennisi, Giuseppe Infantino, Ciro Celsa, Gabriele Di Maria, Marco Enea, Marco Vaccaro, Roberto Cannella, Carlo Ciccioli, Claudia La Mantia, Alessandro Mantovani, Francesco Mercurio, Herbert Tilg, Giovanni Targher, Vito Di Marco, Calogero Cammà, Sal Liver International.2024; 44(11): 2939. CrossRef - Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease outcomes: A call for culturally sensitive interventions: Editorial on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and e
Jae Hyun Bae Clinical and Molecular Hepatology.2024; 30(4): 665. CrossRef - Comparison of Outcomes Between Metabolic Dysfunction-Associated Fatty Liver Disease and Non-alcoholic Fatty Liver Disease: A Meta-Analysis
Ghazala S Virk, Jaahnavi Vajje, Nausheen K Virk, Raam Mannam, Wajeeh Rehman, Naglaa G Ghobriel , Irfan-ud-din Mian, Muhammad Usama Cureus.2023;[Epub] CrossRef - Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study
Zhi-Qin Xie, Hong-Xia Li, Bing-Kun Wang, Zhao-Ming Yang, Zi-Yu Zhang, Wen-Liang Tan, Wen-Xin Li, Qing-Bin Wang, Lei Yang, Hong-Kai Zhuang, Chen-Wei Tang, Chang-Zhen Shang, Ya-Jin Chen European Journal of Internal Medicine.2023; 110: 62. CrossRef - Comparing the Mortality Risk between Metabolic Dysfunction-Associated Fatty Liver Disease and Non-Alcoholic Fatty Liver Disease
Han Na Jung, Chang Hee Jung Diabetes & Metabolism Journal.2023; 47(2): 198. CrossRef - Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis
Hye Jin Chun, Eun Ran Kim, Minyoung Lee, Da Hyun Choi, Soo Hyun Kim, Eugene Shin, Jin-Hong Kim, Jin Won Cho, Dai Hoon Han, Bong-Soo Cha, Yong-ho Lee Metabolism.2023; 145: 155612. CrossRef - Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes
Karl Vaz, Daniel Clayton-Chubb, Ammar Majeed, John Lubel, David Simmons, William Kemp, Stuart K. Roberts Hepatology International.2023; 17(5): 1082. CrossRef - Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Soyeon Shin, Jaeyoung Kim, Ju Yeon Lee, Jun Kim, Chang-Myung Oh Journal of Obesity & Metabolic Syndrome.2023; 32(4): 289. CrossRef
- Metabolic Risk/Epidemiology
- Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
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So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
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Diabetes Metab J. 2022;46(1):140-148. Published online August 9, 2021
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DOI: https://doi.org/10.4093/dmj.2021.0023
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Abstract
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- Background
To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM).
Methods We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age.
Results Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles.
Conclusion In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.
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Citations
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- Advances in free fatty acid profiles in gestational diabetes mellitus
Haoyi Du, Danyang Li, Laura Monjowa Molive, Na Wu Journal of Translational Medicine.2024;[Epub] CrossRef - Modulation of gut microbiota and lipid metabolism in rats fed high-fat diets by Ganoderma lucidum triterpenoids
Aijun Tong, Weihao Wu, Zhengxin Chen, Jiahui Wen, Ruibo Jia, Bin Liu, Hui Cao, Chao Zhao Current Research in Food Science.2023; 6: 100427. CrossRef - Fetal Abdominal Obesity Detected at 24 to 28 Weeks of Gestation Persists until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
Wonjin Kim, Soo Kyung Park, Yoo Lee Kim Diabetes & Metabolism Journal.2021; 45(6): 970. CrossRef
- Basic Research
- Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy
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Guang-Yin Shen, Jeong-Hun Shin, Yi-Sun Song, Hyun-Woo Joo, In-Hwa Park, Jin-Hee Seong, Na-Kyoung Shin, A-Hyeon Lee, Young Jong Cho, Yonggu Lee, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim
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Diabetes Metab J. 2021;45(4):594-605. Published online February 26, 2021
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DOI: https://doi.org/10.4093/dmj.2020.0049
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Abstract
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- Background
We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy.
Methods Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit.
Results G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro.
Conclusion Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.
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Citations
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- Targeting autophagy in diabetic cardiomyopathy: From molecular mechanisms to pharmacotherapy
Jie Li, Yingying Xie, Shuwen Zheng, Haoming He, Zhe Wang, Xuexi Li, Siqi Jiao, Dong Liu, Furong Yang, Hailing Zhao, Ping Li, Yihong Sun Biomedicine & Pharmacotherapy.2024; 175: 116790. CrossRef - Knockout of C1q/tumor necrosis factor-related protein-9 aggravates cardiac fibrosis in diabetic mice by regulating YAP-mediated autophagy
Shiyan Ruan, Jun Li, Shengyun Lei, Shaomeng Zhang, Dan Xu, Anju Zuo, Linxi Li, Yuan Guo Frontiers in Pharmacology.2024;[Epub] CrossRef - Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate‐activated protein kinase/mammalian target of the rapamycin pathway modulation
Xueyao Yang, Xin Zhao, Yanfei Liu, Yue Liu, Libo Liu, Ziyu An, Haoran Xing, Jinfan Tian, Xiantao Song Phytotherapy Research.2023; 37(4): 1377. CrossRef - Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids
Ronghui Han, Hemeng Huang, Weiyi Xia, Jingjin Liu, Hui Luo, Jing Tang, Zhengyuan Xia Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
- Basic Research
- Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell
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Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho
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Diabetes Metab J. 2021;45(2):260-269. Published online July 10, 2020
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DOI: https://doi.org/10.4093/dmj.2019.0191
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Background
Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.
Methods
Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.
Results
Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.
Conclusion
UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.
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- Wharton’s Jelly Mesenchymal Stem Cell Conditioned Medium Ameliorates Diabetes‐Induced Testicular Damage and Sperm Abnormalities by Mitigating Oxidative Stress, Apoptosis, and Inflammation
Mojtaba Sargazi, Narges Karbalaei, Saied Karbalay-Doust, Sara Keshtgar, Zohre Aghaei, Pasquale Marrazzo Stem Cells International.2024;[Epub] CrossRef - Secretome Derived from Mesenchymal Stem/Stromal Cells: A Promising Strategy for Diabetes and its Complications
ling li, Siyu Hua, Lianghui You, Tianying Zhong Current Stem Cell Research & Therapy.2024; 19(10): 1328. CrossRef - Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance
Amnah Al-Sayyar, Maha M. Hammad, Michayla R. Williams, Mohammed Al-Onaizi, Jehad Abubaker, Fawaz Alzaid Metabolites.2023; 13(3): 384. CrossRef - Neuroprotective Effect of Wharton’s Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis
Zohre Aghaei, Narges Karbalaei, Mohammad Reza Namavar, Masoud Haghani, Mahboobeh Razmkhah, Mahdi Khorsand Ghaffari, Marzieh Nemati, Andrea Ballini Stem Cells International.2023; 2023: 1. CrossRef - Mesenchymal-Stem Cell-Derived Conditioned Media Versus Exosomes in the Treatment of Rat Model of Polycystic Ovary: An Attempt to Understand the Underlying Mechanisms (Biochemical and Histological Study)
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Huixue Tang, Huikun Luo, Zihan Zhang, Di Yang Cells.2022; 11(23): 3879. CrossRef - Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach
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- Technology/Device
- Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy
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In-Hwa Park, Yi-Sun Song, Hyun-Woo Joo, Guang-Yin Shen, Jin-Hee Seong, Na-Kyoung Shin, Young Jong Cho, Yonggu Lee, Jeong Hun Shin, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim
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Diabetes Metab J. 2020;44(1):173-185. Published online April 23, 2019
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DOI: https://doi.org/10.4093/dmj.2018.0211
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- Background
Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model. MethodsRats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells. ResultsG-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells. ConclusionOur results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.
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- Clinical Diabetes & Therapeutics
- Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment
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Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
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Diabetes Metab J. 2019;43(2):127-143. Published online April 15, 2019
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DOI: https://doi.org/10.4093/dmj.2019.0034
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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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- Complications
- Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus
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Kyung-Soo Kim, Seok Won Park, Yong-Wook Cho, Soo-Kyung Kim
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Diabetes Metab J. 2018;42(3):224-232. Published online May 31, 2018
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DOI: https://doi.org/10.4093/dmj.2017.0065
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- Background
To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM). MethodsWe investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or the presence of albuminuria. ResultsThe mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m2) and the end of follow-up (52.7±17.5 mL/min/1.73 m2, P<0.001). At the end of follow-up, the prevalence of eGFR <60 mL/min/1.73 m2 had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m2, the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration <5 years (P=0.018). ConclusionCKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.
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- Clinical Care/Education
- Self-Monitoring of Blood Glucose in Patients with Insulin-Treated Type 2 Diabetes Mellitus
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Kyung-Soo Kim
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Diabetes Metab J. 2018;42(1):26-27. Published online February 23, 2018
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DOI: https://doi.org/10.4093/dmj.2018.42.1.26
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- Association between frequency of self-monitoring of blood glucose and glycemic control in patients with type 2 diabetes
Xiaoyan Sun, Xianghai Zhou, Shaobo Li, Linong Ji Diabetes Research and Clinical Practice.2024; 209: 111027. CrossRef - Epidemiological profile and diabetes control of Type 1 Diabetes Mellitus patients in Karbala Governorate, Iraq
Abdul Razzaq Oleiwi Jasim, Noor Abdul Razzaq, Ali Thoulfikar A. Imeer, Rahem Mahdi Rahem, Abdul Amir H. Kadhum, Ahmed A. Al-Amiery F1000Research.2023; 12: 409. CrossRef - Evaluating the impact of self‐monitoring of blood glucose frequencies on glucose control in patients with type 2 diabetes who do not use insulin: A systematic review and meta‐analysis
Yingqi Xu, David Hsien Yung Tan, Joyce Yu‐Chia Lee International Journal of Clinical Practice.2019;[Epub] CrossRef
- The Clinical Characteristics of the Newly Diagnosed Early Onset (< 40 Years Old) Diabetes in Outpatients' Clinic
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Kyung-Soo Kim, Hyun-Ju Oh, Ji-Woon Kim, Yeo-Kyung Lee, Soo-Kyung Kim, Seok-Won Park, Yoo-Lee Kim, Won-Keun Park, Yong-Wook Cho
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Korean Diabetes J. 2010;34(2):119-125. Published online April 30, 2010
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DOI: https://doi.org/10.4093/kdj.2010.34.2.119
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4,886
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Abstract
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- Background
The prevalence of type 2 diabetes in young adults and adolescents has increased in the last decade according to the increasing obese population. The aim of this study was to examine the clinical characteristics of patients diagnosed with diabetes mellitus before the age of 40 years as compared with patients diagnosed at older ages. MethodsThis was a cross-sectional, retrospective study using data from 350 diabetic patients who were diagnosed with diabetes in an outpatient setting between January 2005 and December 2007. Patients were diagnosed according to the criteria set forth by the American Diabetes Association. We examined the clinical characteristics and laboratory data of the patients through review of medical records and compared the early-onset diabetic patients (< 40 years old) and the usual-onset diabetic patients (≥ 40 years old). ResultsThe frequency of early-onset diabetes and usual-onset diabetes were 31.1% (n=109) and 68.9% (n=241), respectively. The early-onset diabetic patients more often had a positive family history of diabetes; higher HbA1c, fasting glucose, and postprandial glucose levels; experienced typical symptoms more frequently; had microalbuminuria more frequently; and required insulin therapy as initial treatment more frequently as compared to usual-onset diabetic patients, and these differences were significant. Conversely, hypertension was significantly more common in the usual-onset diabetic patients. ConclusionIt could be concluded that we should control early onset diabetes more strictly to prevent its complication because early onset diabetic patients represented more severe hyperglycemia and had more prevalent microalbuminuria.
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Hamid Ashraf, Ahmad Faraz, Jamal Ahmad International Journal of Diabetes in Developing Countries.2021; 41(3): 396. CrossRef - Questionnaire-based Survey of Demographic and Clinical Characteristics, Health Behaviors, and Mental Health of Young Korean Adults with Early-Onset Diabetes
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