Diabetes & Metabolism Journal

Original Articles

Basic Research
Macrophage-Specific Progranulin Deficiency Prevents Diet-Induced Obesity through the Inhibition of Hypothalamic and Adipose Tissue Inflammation: Chan Hee Lee, Chae Beom Park, Hyun-Kyong Kim, Won Hee Jang, Se Hee Min, Jae Bum Kim, Min-Seon Kim; Received August 17, 2024 Accepted October 23, 2024 Published online March 11, 2025; DOI: https://doi.org/10.4093/dmj.2024.0486 [Epub ahead of print]

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Chronic low-grade inflammation in multiple metabolic organs contributes to the development of insulin resistance induced by obesity. Progranulin (PGRN) is an evolutionarily-conserved secretory protein implicated in immune modulation. The generalized deletion of the PGRN-encoded Grn gene improves insulin resistance and glucose intolerance in obese mice fed a high-fat diet (HFD). However, it remains unclear which cells or organs are responsible for the beneficial metabolic effect of Grn depletion.
Methods
Considering the critical role of macrophages in HFD-induced obesity and inflammation, we generated mice with a macrophage-specific Grn depletion (Grn-MΦKO mice) by mating lysozyme M (LysM)-Cre and Grn-floxed mice. Body weight, food intake, energy expenditure, and glucose and insulin tolerance were compared between Grn-MΦKO mice and their wildtype (WT) controls under normal chow diet (NCD)- or HFD-fed conditions. We also examined macrophage activation and inflammation- related gene expression in the visceral adipose tissue and hypothalamus along with insulin and leptin signaling.
Results
Grn-MΦKO mice showed no alteration in metabolic phenotypes under NCD-fed conditions. However, upon HFD feeding, these mice exhibited less weight gain and improved glucose and insulin tolerance compared to WT mice. Moreover, HFD-induced macrophage activation and proinflammatory cytokine expression were significantly reduced in both the adipose tissue and hypothalamus of Grn-MΦKO mice, while HFD-induced impairments in leptin and insulin signaling showed improvement.
Conclusion
Macrophage-derived PGRN and possibly other Grn products play a critical role in the development of HFD-induced obesity, tissue inflammation, and impaired hormonal signaling in both central and peripheral metabolic organs.

Type 1 Diabetes
Global Burden of Type 1 Diabetes Mellitus Related Chronic Kidney Disease among Adolescents and Young Adults, and Projections to 2035: Results from the Global Burden of Disease Study 2021: Xiaoli Qu, Chongbin Liu, Lin Sun, Zhifeng Sheng; Received September 4, 2024 Accepted December 12, 2024 Published online March 10, 2025; DOI: https://doi.org/10.4093/dmj.2024.0544 [Epub ahead of print]

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Type 1 diabetes mellitus related chronic kidney disease (T1DM-CKD) presents a global health challenge, with unclear trends and patterns among adolescents and young adults. This study analyzed the burden and risk factors of T1DM-CKD in individuals aged 15 to 39 from 1990 to 2021 and predicted future trends.
Methods
Using data from the Global Burden of Disease (GBD) study 2021, we analyzed the prevalence, incidence, mortality, disability-adjusted life years (DALYs), and average annual percentage change (AAPC) of T1DM-CKD among youth across gender, sociodemographic index (SDI) areas, and data from 21 regions and 204 countries and territories. Risk factors were assessed and future trends were projected.
Results
Between 1990 and 2021, the global prevalence of T1DM-CKD aged 15 to 39 increased by 107.5% to 3.32 million, with an age-standardized prevalence rate (ASPR) of 111.44 per 100,000 (AAPC 1.33%). Incidence rose by 165.4% to 14,200, with an agestandardized incidence rate of 0.48 per 100,000 (AAPC 2.19%). However, age-standardized mortality rate (0.50 per 100,000, AAPC –0.87%) and age-standardized DALYs rate (30.61 per 100,000, AAPC –0.83%) decreased. ASPR increased across all SDI regions, especially in high-SDI countries. High fasting glucose remained the major risk factor influencing DALYs. By 2035, T1DM-CKD prevalence was projected to decrease to 2.86 million (ASPR 89.67 per 100,000).
Conclusion
The research revealed a global increase in T1DM-CKD among youth, with a shift towards younger onset and significant variations based on gender and location, emphasizing the importance of early prevention and management strategies for this demographic.

Guideline/Statement/Fact Sheet
Prevalence, Incidence, and Metabolic Characteristics of Young Adults with Type 2 Diabetes Mellitus in South Korea (2010–2020): Ji Yoon Kim, Jiyoon Lee, Joon Ho Moon, Se Eun Park, Seung-Hyun Ko, Sung Hee Choi, Nam Hoon Kim; Diabetes Metab J. 2025;49(2):172-182. Published online March 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0826

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This study aimed to examine trends in the prevalence, incidence, metabolic characteristics, and management of type 2 diabetes mellitus (T2DM) among young adults in South Korea.
Methods
Young adults with T2DM were defined as individuals aged 19 to 39 years who met the diagnostic criteria for T2DM. Data from the Korean National Health Insurance Service-Customized Database (2010–2020, n=225,497–372,726) were analyzed to evaluate trends in T2DM prevalence, incidence, metabolic profiles, comorbidities, and antidiabetic drug prescription. Additional analyses were performed using the Korea National Health and Nutrition Examination Survey.
Results
The prevalence of T2DM in young adults significantly increased from 1.02% in 2010 to 2.02% in 2020 (P<0.001), corresponding to 372,726 patients in 2020. Over the same period, the incidence rate remained stable within the range of 0.36% to 0.45%. Prediabetes prevalence steadily increased from 15.53% to 20.92%, affecting 3.87 million individuals in 2020. The proportion of young adults with T2DM who were obese also increased, with 67.8% having a body mass index (BMI) ≥25 kg/m² and 31.6% having a BMI ≥30 kg/m² in 2020. The prevalence of hypertension, dyslipidemia, and fatty liver disease also increased, reaching 34.2%, 79.8%, and 78.9%, respectively, in 2020. Although the overall pharmacological treatment rate remained low, the prescription of antidiabetic medications with weight-reducing properties increased over the study period.
Conclusion
The prevalence of T2DM among young adults in South Korea nearly doubled over the past decade. The strong association with obesity and metabolic comorbidities emphasizes the urgent need for targeted prevention and management strategies tailored to this population.

Metabolic Risk/Epidemiology
Trends in Metabolically Unhealthy Obesity by Age, Sex, Race/Ethnicity, and Income among United States Adults, 1999 to 2018: Wen Zeng, Weijiao Zhou, Junlan Pu, Juan Li, Xiao Hu, Yuanrong Yao, Shaomei Shang; Received July 5, 2024 Accepted September 27, 2024 Published online February 25, 2025; DOI: https://doi.org/10.4093/dmj.2024.0364 [Epub ahead of print]

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This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018.
Methods
We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m² with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO.
Results
The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups.
Conclusion
This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.

Basic Research
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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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
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; Diabetes Metab J. 2025;49(2):298-310. Published online February 4, 2025; DOI: https://doi.org/10.4093/dmj.2024.0239

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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.

Citations

Citations to this article as recorded by

Investigation of the Potential Association Between Atherosclerotic Cardiovascular Disease Risk Score and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study
Chrysa Agapitou, Theodoros N. Sergentanis, Effie G. Papageorgiou, Panagiotis Theodossiadis, Ignatios Ikonomidis, Vaia Lambadiari, Irini Chatziralli
Biomedicines.2025; 13(3): 633. CrossRef

Pharmacotherapy
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; Diabetes Metab J. 2025;49(2):225-234. Published online January 6, 2025; DOI: https://doi.org/10.4093/dmj.2024.0238

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Abstract PDF Supplementary Material PubReader 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.

Lifestyle and Behavioral Interventions
Impact of Meal Frequency on Insulin Resistance in Middle-Aged and Older Adults: A Prospective Cohort Study: Ha-Eun Ryu, Jong Hee Lee, Byoungjin Park, Seok-Jae Heo, Yu-Jin Kwon; Diabetes Metab J. 2025;49(2):311-320. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0407

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Insulin resistance (IR) is central to metabolic disorders and significantly influenced by diet. Studies on meal frequency (MF) and metabolic indicators have shown mixed results. This study explores the link between MF and IR in middle-aged and older adults.
Methods
This prospective cohort study included 4,570 adults aged 40 to 69 years from the Korean Genome and Epidemiologic Study. MF were divided into two groups based on whether they consumed three or more, or fewer than three, meals daily. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR); participants were classified as IR if their HOMA-IR value was ≥2.5. Multiple Cox proportional hazard regression analyses were conducted to examine the association between MF and the incidence of IR.
Results
After adjusting for all variables, individuals in the MF ≥3 group showed a reduced incidence of IR compared to those in the MF <3 group (hazard ratio, 0.880; 95% confidence interval, 0.782 to 0.990). Additionally, subgroup analyses by sex, diabetes mellitus (DM), and body mass index (BMI) showed that this association persisted only in men, individuals without DM, and those with a BMI <25.
Conclusion
Our findings indicate that a higher MF among middle-aged and older adults is associated with a reduced incidence of IR. However, this association was maintained only in men, individuals without DM, and those without obesity.

Basic and Translational Research
Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage: Yuan Tian, Zhiqiang Zhu, Jun Qiao, Bei Liu, Yuehai Xiao; Diabetes Metab J. 2025;49(2):210-224. Published online November 6, 2024; DOI: https://doi.org/10.4093/dmj.2024.0099

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Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD.
Methods
Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot.
Results
Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression.
Conclusion
Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Review

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

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

Citations

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Bioelectrical impedance analysis parameters are superior to liver enzymes in predicting metabolic dysfunction-associated steatotic liver disease in young adults
Kyungchul Song, Yu-Jin Kwon, Eunju Lee, Hye Sun Lee, Young Hoon Youn, Su Jung Baik, Hana Lee, Joon Young Kim, Youngha Choi, Hyun Wook Chae
Internal and Emergency Medicine.2025; 20(3): 785. CrossRef

Original Articles

Cardiovascular Risk/Epidemiology
Cardiovascular Disease & Diabetes Statistics in Korea: Nationwide Data 2010 to 2019: Jin Hwa Kim, Junyeop Lee, Kyungdo Han, Jae-Taek Kim, Hyuk-Sang Kwon, on Behalf of the Diabetic Vascular Disease Research Group of the Korean Diabetes Association; Diabetes Metab J. 2024;48(6):1084-1092. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0275

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Background
This study aimed to provide updated insights into the incidence and management of cardiovascular disease (CVD) in Korean adults with diabetes.
Methods
Using data from the Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey, we analyzed the representative national estimates of CVD in adults with diabetes.
Results
The age- and sex-standardized incidence rate of ischemic heart disease (IHD), ischemic stroke, and peripheral artery disease (PAD) decreased from 2010 to 2019 in individuals with type 2 diabetes mellitus (T2DM). However, an increase in the incidence of heart failure (HF) was observed during the same period. Only 4.96% of adults with diabetes and CVD achieved optimal control of all three risk factors (glycemic levels, blood pressure, and lipid control). Additionally, high-intensity statin treatment rates were 8.84% and 9.15% in individuals with IHD and ischemic stroke, respectively. Treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a glucagon-like peptide-1 receptor agonist (GLP-1RA) was relatively low in 2019, with only 11.87%, 7.10%, and 11.05% of individuals with IHD, ischemic stroke, and HF, respectively, receiving SGLT2i treatment. Furthermore, only 1.08%, 0.79%, and 1.06% of patients with IHD, ischemic stroke, and HF, respectively, were treated with GLP-1RA.
Conclusion
The incidence of most CVD (IHD, ischemic stroke, and PAD) decreased between 2010 and 2019, whereas the incidence of HF increased. The overall use of high-intensity statins, SGLT2i, and GLP-1RA remained low among individuals with T2DM and CVD.

Citations

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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 & Metabolism Journal.2025; 49(1): 13. CrossRef

Metabolic Risk/Epidemiology
Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents: Kyungchul Song, Eunju Lee, Hye Sun Lee, Hana Lee, Ji-Won Lee, Hyun Wook Chae, Yu-Jin Kwon; Diabetes Metab J. 2025;49(2):264-274. Published online October 29, 2024; DOI: https://doi.org/10.4093/dmj.2024.0302

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Abstract PDF Supplementary Material PubReader ePub: Background
Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population.
Methods
Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points.
Results
All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point.
Conclusion
SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Cardiovascular Risk/Epidemiology
Impact of New-Onset Diabetes after Transplantation on Cardiovascular Risk and Mortality in Korea: A Nationwide Population-Based Study: Seung Shin Park, Bo Kyung Koo, Sanghyun Park, Kyungdo Han, Min Kyong Moon; Diabetes Metab J. 2025;49(1):117-127. Published online September 12, 2024; DOI: https://doi.org/10.4093/dmj.2024.0078

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Background
Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL.
Methods
Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis.
Results
A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment.
Conclusion
NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.

Citations

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New Onset Diabetes After Organ Transplantation: Risk Factors, Treatment, and Consequences
Lucija Popović, Tomislav Bulum
Diagnostics.2025; 15(3): 284. CrossRef

Review

Others
T-Cell Senescence in Human Metabolic Diseases: Ha Thi Nga, Thi Linh Nguyen, Hyon-Seung Yi; Diabetes Metab J. 2024;48(5):864-881. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0140

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Immunosenescence denotes a state of dysregulated immune cell function characterized by a confluence of factors, including arrested cell cycle, telomere shortening, markers of cellular stress, mitochondrial dysfunction, loss of proteostasis, epigenetic reprogramming, and secretion of proinflammatory mediators. This state primarily manifests during the aging process but can also be induced in various pathological conditions, encompassing chronic viral infections, autoimmune diseases, and metabolic disorders. Age-associated immune system alterations extend to innate and adaptive immune cells, with T-cells exhibiting heightened susceptibility to immunosenescence. In particular, senescent T-cells have been identified in the context of metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Recent investigations suggest a direct link between T-cell senescence, inflammation, and insulin resistance. The perturbation of biological homeostasis by senescent T-cells appears intricately linked to the initiation and progression of metabolic diseases, particularly through inflammation-mediated insulin resistance. Consequently, senescent T-cells are emerging as a noteworthy therapeutic target. This review aims to elucidate the intricate relationship between metabolic diseases and T-cell senescence, providing insights into the potential roles of senescent T-cells in the pathogenesis of metabolic disorders. Through a comprehensive examination of current research findings, this review seeks to contribute to a deeper understanding of the complex interplay between immunosenescence and metabolic health.

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Elena Bartoloni, Fabio Cacciapaglia, Gian Luca Erre, Elisa Gremese, Andreina Manfredi, Matteo Piga, Garifallia Sakellariou, Francesca Romana Spinelli, Ombretta Viapiana, Fabiola Atzeni
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T cell aging and exhaustion: Mechanisms and clinical implications
Weiqi Zhang, Dejun Kong, Xiaohan Zhang, Lu Hu, Yeqi Nian, Zhongyang Shen
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Global research trends in inflammaging from 2005 to 2024: a bibliometric analysis
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Original Article

Cardiovascular Risk/Epidemiology
Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases: Cheng Yang, Cheng-Gang Zhu, Yuan-Lin Guo, Na-Qiong Wu, Qian Dong, Rui-Xia Xu, Yong-Jian Wu, Jie Qian, Jian-Jun Li; Diabetes Metab J. 2024;48(5):993-1002. Published online August 21, 2024; DOI: https://doi.org/10.4093/dmj.2023.0410

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Abstract PDF Supplementary Material PubReader ePub: Background
Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states.
Methods
In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality.
Results
Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05).
Conclusion
The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.

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