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Complications
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Connection between Impaired Fasting Glucose or Type 2 Diabetes Mellitus and Sepsis: A 10-Year Observational Data from the National Health Screening Cohort
Eun Hwa Lee, Kyoung Hwa Lee, Kyu-na Lee, Yebin Park, Kyung Do Han, Sang Hoon Han
Received July 16, 2024  Accepted October 23, 2024  Published online February 17, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0387    [Epub ahead of print]
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AbstractAbstract PDF
Background
The mortality of sepsis without direct drugs is high. The association between prediabetes, based on a single fasting glucose (FG), or long-term type 2 diabetes mellitus (T2DM) and sepsis remains unclear.
Methods
Of the adults aged ≥20 years who were included in the National Health Screening Program (NHSP) in 2009, 40% were randomly sampled. After excluding patients with type 1 diabetes mellitus, with missing information, and who were diagnosed with sepsis during the wash-out (between 2001 and the NHSP) or 1-year lag period, a cohort comprised of 3,863,323 examinees. Body mass index (BMI) measurements, FG tests, and self-reported questionnaires on health-related behaviors were conducted. Individual information was followed up until 2020 and censored upon the first occurrence of sepsis or death. The incidence of sepsis was compared using a multivariable regression adjusted for age, sex, income, BMI, smoking, drinking, physical activity levels, and chronic diseases.
Results
The cohort was divided into those with normal FG (n=2,675,476), impaired fasting glucose (IFG) (n=890,402, 23.0%), T2DM <5 years (n=212,391, 5.5%), or T2DM for ≥5 years (n=85,054, 2.2%). The groups with IFG (adjusted hazard ratio [aHR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), T2DM <5 years (aHR, 1.43; 95% CI, 1.40 to 1.47), and T2DM for ≥5 years (aHR, 1.82; 95% CI, 1.77 to 1.87) exhibited significantly higher incidence of sepsis (P<0.001), with the greatest risk in patients with T2DM aged <40 years (aHR, 1.96; 95% CI, 1.71 to 2.25).
Conclusion
Patients with long-standing and young-onset T2DM show a substantially high risk of sepsis, emphasizing the need for infection prevention and vaccination.
Metabolic Risk/Epidemiology
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The Impact of Obesity on the Association between Parity and Risk of Type 2 Diabetes Mellitus
Yuki Gen, Kyuho Kim, Joonyub Lee, Junyoung Jung, Sang-Hyuk Jung, Hong-Hee Won, Dokyoon Kim, Yun-Sung Jo, Yu-Bae Ahn, Seung-Hyun Ko, Jae-Seung Yun
Received September 5, 2024  Accepted November 15, 2024  Published online February 14, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0536    [Epub ahead of print]
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AbstractAbstract PDF
Background
Most studies focus solely on the relationship between parity and type 2 diabetes mellitus (T2DM) risk, providing limited insights into other contributing or protective factors. This study aims to explore the complex relationship between parity and T2DM risk, considering additional factors such as obesity, race, and body composition.
Methods
This prospective cohort study used data from 242,159 women aged 40 to 69 from the UK Biobank, none of whom had T2DM at baseline. Multivariable Cox proportional hazard models were applied to assess the association between parity and T2DM. Subgroup analyses were performed based on body mass index (BMI), waist circumference (WC), and race.
Results
The hazard ratio for T2DM per additional child was 1.16 (95% confidence interval, 1.13 to 1.16). Subgroup analysis revealed that Asian women and those with obesity or abdominal obesity had a higher risk of T2DM associated with multiparity. No increased risk was observed in women with normal BMI or WC. Mediation analysis showed that WC and BMI significantly mediated the parity-T2DM relationship, accounting for 49% and 38% of the effect, respectively.
Conclusion
There is a clear positive association between multiparity and T2DM risk, particularly in Asian women and those with obesity. Maintaining normal BMI and WC appears to mitigate this risk, highlighting the importance of weight management for women at higher parity levels. These findings offer crucial insights for public health interventions aimed at reducing T2DM risk among women.
Others
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Contributions of Hepatic Insulin Resistance and Islet β-Cell Dysfunction to the Blood Glucose Spectrum in Newly Diagnosed Type 2 Diabetes Mellitus
Mengge Yang, Ying Wei, Jia Liu, Ying Wang, Guang Wang
Received September 5, 2024  Accepted December 12, 2024  Published online February 13, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0537    [Epub ahead of print]
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AbstractAbstract PDF
Background
Our previous studies have investigated the role of hepatic insulin resistance (hepatic IR) and islet β-cell function in the pathogenesis of diabetes. This study aimed to explore the contributions of hepatic IR and islet β-cell dysfunction to the blood glucose spectrum in patients with newly diagnosed type 2 diabetes mellitus.
Methods
Hepatic IR was assessed by the hepatic insulin resistance index (HIRI). Islet β-cell function was assessed by insulin secretion- sensitivity index-2 (ISSI2). The associations between blood glucose spectrum and hepatic IR and ISSI2 were analyzed.
Results
A total of 707 patients with new-onset diabetes were included. The fasting blood glucose (FBG) and 30 minutes postload blood glucose elevated with rising HIRI (both P for trend <0.001). The FBG, 30 minutes, 2 hours, and 3 hours post-load blood glucose elevated with decreasing ISSI2 quartiles (all P for trend <0.001). There was a negative correlation between ISSI2 and HIRI after adjusting blood glucose levels (r=–0.199, P<0.001).
Conclusion
Hepatic IR mainly contributed to FBG and early-phase postprandial plasma glucose, whereas β-cell dysfunction contributed to fasting and postprandial plasma glucose at each phase.
Brief Report
Others
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Alpha-Tocopherol-Loaded Liposomes Reduce High Glucose Induced Oxidative Stress in Schwann Cells: A Proof of Concept Study
Jee-In Heo, Mi Jeong Kim, Daehyun Kim, Jimin Seo, Joon Ho Moon, Sung Hee Choi, Hak Jong Lee, Tae Jung Oh
Received August 19, 2024  Accepted October 23, 2024  Published online February 5, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0489    [Epub ahead of print]
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AbstractAbstract PDF
Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.
Original Articles
Basic Research
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Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease
Inseon Hwang, Jung Eun Nam, Wonsuk Choi, Won Gun Choi, Eunji Lee, Hyeongseok Kim, Young-Ah Moon, Jun Yong Park, Hail Kim
Received April 26, 2024  Accepted September 21, 2024  Published online February 5, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0215    [Epub ahead of print]
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AbstractAbstract PDF
Background
Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine neurotransmitter that has various functions in central and peripheral tissues. While 5-HT is known to regulate various biological processes in liver, direct role of 5-HT and its receptors, especially 5-HT receptor 2A (HTR2A) and HTR2B, in development and progression of alcoholic liver disease (ALD) in vivo is not well understood.
Methods
Blood 5-HT level was measured from both human ALD patients and ethanol (EtOH) diet-fed mouse models. Gut-specific tryptophan hydroxylase 1 (Tph1) knockout mice, liver-specific Htr2a knockout mice, and liver-specific Htr2b knockout mice were fed with EtOH diet. Then we evaluated liver damage, hepatic steatosis, endoplasmic reticulum (ER) stress, and inflammation.
Results
Blood 5-HT concentrations are increased in both humans and mice with ALD. Both gut-specific Tph1 knockout and liver- specific Htr2a knockout mice are resistant to steatosis by down-regulating lipogenic pathways in liver of chronic EtOH diet-fed mice. Moreover, genetic inhibition of both gut-derived serotonin (GDS) synthesis and hepatic HTR2A signaling prevents ER stress in liver of chronic EtOH diet-fed mice. Additionally, we found that ablation of HTR2A signaling protects against disease progression by attenuating liver injury and inflammation in chronic plus binge EtOH diet-fed mice. Also, inhibiting HTR2A signaling ameliorates alcohol-induced liver injury and ER stress in an acute EtOH diet-fed mice model.
Conclusion
GDS directly regulates lipogenesis and ER stress via signaling through hepatic HTR2A in the context of ALD. Inhibiting HTR2A signaling protects against alcohol-induced steatosis, liver injury and disease progression in various ALD mouse models and may also provide a novel therapeutic strategy for ALD.
Complications
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Does 10-Year Atherosclerotic Cardiovascular Disease Risk Predict Incident Diabetic Nephropathy and Retinopathy in Patients with Type 2 Diabetes Mellitus? Results from Two Prospective Cohort Studies in Southern China
Jiaheng Chen, Yu Ting Li, Zimin Niu, Zhanpeng He, Yao Jie Xie, Jose Hernandez, Wenyong Huang, Harry H.X. Wang, on Behalf of the Guangzhou Diabetic Eye Study Group
Received May 10, 2024  Accepted October 23, 2024  Published online February 4, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0239    [Epub ahead of print]
  • 292 View
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AbstractAbstract PDF
Background
Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability.
Results
During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women.
Conclusion
Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.
Basic Research
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Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization
Li Jiang, Jie Jian, Xulin Sai, Xiai Wu
Received May 5, 2024  Accepted September 7, 2024  Published online January 24, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0233    [Epub ahead of print]
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AbstractAbstract PDF
Background
Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.
Methods
Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.
Results
The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.
Conclusion
VCAN showed the prospects into DKD pathology and clinical indicator.
Basic Research
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Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei Wang, Shuai Huang, Li Zhang, Yixian He, Xian Shao, A-Shan-Jiang A-Ni-Wan, Yan Kong, Xuying Meng, Pei Yu, Saijun Zhou
Received July 18, 2024  Accepted September 7, 2024  Published online January 23, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0398    [Epub ahead of print]
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AbstractAbstract PDF
Background
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
Cardiovascular Risk/Epidemiology
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Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study
Honglin Sun, Zhenyu Wu, Guang Wang, Jia Liu
Received May 2, 2024  Accepted November 15, 2024  Published online January 20, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0100    [Epub ahead of print]
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AbstractAbstract PDF
Background
Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort.
Methods
This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed.
Results
During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders.
Conclusion
High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.
Drug/Regimen
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Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon Kim, Soo Lim, In-Kyung Jeong, Eun-Jung Rhee, Jun Sung Moon, Ohk-Hyun Ryu, Hyuk-Sang Kwon, Jong Chul Won, Sang Soo Kim, Sang Yong Kim, Bon Jeong Ku, Heung Yong Jin, Sin Gon Kim, Bong-Soo Cha, on Behalf of Investigators of ENVELOP Study
Received May 9, 2024  Accepted August 14, 2024  Published online January 6, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0238    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
Editorial
Diabetes in Korean Adults: Prevalence, Management, and Comorbidities
Sung Hoon Yu
Diabetes Metab J. 2025;49(1):22-23.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0844
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Original Article
Guideline/Statement/Fact Sheet
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Diabetes Fact Sheets in Korea 2024
Se Eun Park, Seung-Hyun Ko, Ji Yoon Kim, Kyuho Kim, Joon Ho Moon, Nam Hoon Kim, Kyung Do Han, Sung Hee Choi, Bong Soo Cha
Diabetes Metab J. 2025;49(1):24-33.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0818
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to investigate the prevalence, management, and comorbidities of diabetes mellitus among Korean adults.
Methods
Data from the Korea National Health and Nutrition Examination Survey (2019–2022) were analyzed to assess the prevalence, treatment, risk factors, and comorbidities of diabetes. Comparisons between young and older adults with diabetes were emphasized.
Results
Among Korean adults aged ≥30 years, the prevalence of diabetes is 15.5% during 2021–2022. Of these, 74.7% were aware of their condition, 70.9% received antidiabetic treatment, and only 32.4% achieved glycosylated hemoglobin (HbA1c) <6.5%. Moreover, 15.9% met the integrated management targets, which included HbA1c <6.5%, blood pressure <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL. In young adults aged 19 to 39 years, the prevalence of diabetes was 2.2%. Among them, 43.3% were aware of their condition, 34.6% received treatment, and 29.6% achieved HbA1c <6.5%. Obesity affected 87.1%, and 26.9% had both hypertension and hypercholesterolemia. Among adults aged ≥65 years, the prevalence of diabetes was 29.3%, with awareness, treatment, and control rates of 78.8%, 75.7%, and 31.2%, respectively. Integrated management targets (HbA1c <7.5%, hypertension, and lipids) were achieved by 40.1%.
Conclusion
Diabetes mellitus remains highly prevalent among Korean adults, with significant gaps in integrated glycemic, blood pressure, and lipid control. Older adults with diabetes show higher awareness and treatment rates but limited integrated management outcomes. Young adults with diabetes bear a significant burden of obesity and comorbidities, alongside low awareness and treatment rates. Therefore, early intervention programs, education, and strategies tailored to younger populations are urgently required.

Citations

Citations to this article as recorded by  
  • Diabetes in Korean Adults: Prevalence, Management, and Comorbidities
    Sung Hoon Yu
    Diabetes & Metabolism Journal.2025; 49(1): 22.     CrossRef
Sulwon Lecture 2024
Basic and Translational Research
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Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Il Rae Park, Yong Geun Chung, Kyu Chang Won
Diabetes Metab J. 2025;49(1):1-12.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0796
  • 1,335 View
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AbstractAbstract PDFPubReader   ePub   
Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.
Response
Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes (Diabetes Metab J 2024;48:885-900)
Junfei Gu, Xinjie Zhang, Qunye Zhang, Zhe Wang
Diabetes Metab J. 2025;49(1):162-164.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0785
  • 328 View
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Review
Others
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Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database
Kyung-Soo Kim, Bongseong Kim, Kyungdo Han
Diabetes Metab J. 2025;49(1):13-21.   Published online January 1, 2025
DOI: https://doi.org/10.4093/dmj.2024.0780
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
The Korean National Health Information Database (NHID), which contains nationwide real-world claims data including sociodemographic data, health care utilization data, health screening data, and healthcare provider information, is a powerful resource to test various hypotheses. It is also longitudinal in nature due to the recommended health checkup every 2 years and is appropriate for long-term follow-up study as well as evaluating the relationships between health outcomes and changes in parameters such as lifestyle factors, anthropometric measurements, and laboratory results. However, because these data are not collected for research purposes, precise operational definitions of diseases are required to facilitate big data analysis using the Korean NHID. In this review, we describe the characteristics of the Korean NHID, operational definitions of diseases used for research related to diabetes, and introduce representative research for diabetes-related diseases using the Korean NHID.

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