Diabetes & Metabolism Journal

Review

Basic and Translational Research
Redefining β-Cell Function in Type 2 Diabetes Mellitus: From Comprehensive Assessment to Precision Medicine: YongKyung Kim, Joon Ha, Jun Sung Moon; Diabetes Metab J. 2026;50(2):235-252. Published online March 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0034

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Abstract PDF PubReader ePub: The global surge in type 2 diabetes mellitus (T2DM) requires a thorough understanding of pancreatic β-cell dysfunction, which remains a central determinant of the disease. However, the evaluation of β-cell insulin secretory capacity is often challenging in clinical practice due to its inherent complexity. This review presents a comprehensive technical overview of diverse assessment methodologies, ranging from conventional fasting-based indices and glucose tolerance tests to advanced mathematical modeling and artificial intelligence-driven approaches. A detailed examination of the methodological strengths and limitations of these various tools is provided to guide their appropriate clinical application. Furthermore, we explore the clinical implications of these assessments in enhancing diagnostic accuracy and tailoring therapeutic strategies. Particular emphasis is placed on the pivotal role of β-cell function evaluation in predicting and achieving diabetes remission—an emerging clinical priority. By integrating the technical landscape of β-cell assessment with practical applications, this review provide a structured framework for optimizing T2DM management and improving long-term patient outcomes.

Original Articles

Lifestyle and Behavioral Interventions
Association between Changes in Physical Activity and Incident Depression among Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Sangwoo Park, Back Kim, Hye Jun Kim, Sun Jae Park, Jihun Song, Jina Chung, Seogsong Jeong, Sang Min Park, Dae Ho Lee, Soo Jung Choi; Received August 17, 2025 Accepted December 18, 2025 Published online February 23, 2026; DOI: https://doi.org/10.4093/dmj.2025.0766 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study aims to investigate the relationship between changes in physical activity patterns following a new diagnosis of type 2 diabetes mellitus (T2DM) and the risk of developing depression.
Methods
This study utilized comprehensive diabetes data from the National Health Insurance Service of South Korea. From this dataset, we included 254,619 individuals newly diagnosed with T2DM between 2009 and 2015 who had health examination data within 2 years before and after their diagnosis date and no prior history of depression. Physical activity levels were quantified using the metabolic equivalent of task (MET) method.
Results
Compared to individuals with 0 MET-min/wk of physical activity prior to a new T2DM diagnosis, those who increased their activity levels to 500–999 MET-min/wk after diagnosis showed a 23% reduction in the risk of depression, while an increase to ≥1,000 MET-min/wk was associated with a 25% reduction in depression risk. Conversely, individuals with 1–499 MET-min/wk before diagnosis who became inactive after diagnosis experienced a 25% increased risk of depression. A similar trend of increased depression risk was observed in those who reduced their physical activity from 500–999 or ≥1,000 MET-min/wk.
Conclusion
Changes in physical activity levels before and after a new diagnosis of T2DM significantly influence the risk of developing depression, with increased activity reducing the risk and decreased activity elevating the risk. This finding underscores the importance of encouraging physical activity to support mental health in patients with newly diagnosed T2DM.

Metabolic Risk/Epidemiology
Birth Weight, Adult Fat Distribution, and Type 2 Diabetes Mellitus Risk: Sex-Specific Study in a Large Prospective Cohort: Ding Ding, Xiaoyi Luo, Shuhao Chen, Zhilin Liu, Xiaojing Kuang, Tianrui Zhuang, Gaoli She, Hailan Huang, Xingfen Yang, Jie Li, Ran An; Received June 29, 2025 Accepted October 23, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0569 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Regional fat distribution is a key determinant of metabolic risk, independent of total adiposity. However, the developmental origins of fat depot-specific accumulation and its contribution to type 2 diabetes mellitus (T2DM) remain unclear. We aimed to investigate whether adult fat distribution mediates the association between birth weight (BW) and T2DM risk.
Methods
We analyzed 30,718 diabetes-free UK Biobank participants with magnetic resonance imaging/dual-energy X-ray absorptiometry derived measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and gynoid adipose tissue (GAT), liver fat fraction (LFF), pancreatic fat fraction (PFF), and muscle fat infiltration (MFI). Fat depots were adjusted for body mass index (BMI) using sex-specific residuals. Cox regression assessed associations of BW and fat depots with T2DM risk. Mediation analysis assessed indirect effects of fat distribution.
Results
Lower BW was associated with a higher risk of T2DM (hazard ratio per 1 kg increase, 0.71; 95% confidence interval, 0.64 to 0.79), with stronger effects in women. Lower BW was linked to greater VAT, LFF, and PFF, and lower GAT, independent of BMI. Higher levels of VAT, LFF, and PFF were associated with increased T2DM risk, while GAT was protective. Mediation analysis revealed that fat distribution partially mediated the BW-T2DM relationship, with LFF showing the strongest mediation effect (11%). Mediation patterns differed by sex: LFF and VAT were the predominant mediators in women, while LFF and GAT contributed substantially in men.
Conclusion
Fat distribution—particularly liver and visceral fat—partially mediates the BW-T2DM relationship, independent of BMI. These findings highlight the clinical importance of fat depot profiling in understanding the developmental origins of diabetes and guiding early risk stratification.

Complications
Optimizing Early Detection of Diabetic Kidney Disease through Synergistic Biomarkers and Serum Metabolites in Human: Xianke Zhou, Yuan Gui, Jia-Jun Liu, Shijia Liu, Dongning Liang, Yuanyuan Wang, Henry Wells Shaffer, Samantha Mae Mallari, Cameron Jones, Priya Gupta, Dier Li, Ke Zhang, Ying Yu, Jianling Tao, Yanlin Wang, Silvia Liu, Dong Zhou, Haiyan Fu; Received March 8, 2025 Accepted September 16, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0193 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetic kidney disease (DKD) progresses to end-stage renal disease more rapidly than chronic kidney disease due to persistent hyperglycemia and early activation of multiple pathways. Early detection of DKD is crucial to identify subtle kidney damage before clinical symptoms appear.
Methods
This study combined human serum proteomics and public single-cell RNA sequencing and spatial transcriptomics data from diabetic kidneys to identify key biomarkers for DKD diagnosis. These biomarkers were validated in multiple organs of db/db mice at early and advanced stages. In a discovery cohort, sera from 173 healthy adults and 444 type 2 diabetes mellitus (T2DM) patients, with or without kidney disease, were analyzed using metabolomics and enzyme-linked immunosorbent assay (ELISA). Multiple machine learning algorithms were developed to integrate synergistic biomarkers and serum metabolites for DKD early detection, with results validated in 435 participants from four independent clinical cohorts.
Results
Metalloproteinase-7 (MMP-7) and tenascin C (TNC) were elevated in human diabetic kidneys at the single-cell and spatial levels. Proteomics indicated upregulation of serum amyloid A1 (SAA1) and TNC in DKD patients’ serum. In db/db mice, all three biomarkers increased in multiple organs by 18 weeks of age. In DKD patient sera, MMP-7 and TNC levels were consistently elevated across cohorts. The new algorithms combining MMP-7, SAA1, and TNC enhanced early-stage DKD detection, with about 13% improvements in accuracy when serum metabolites were included to distinguish the progression from early to advanced stages after DKD.
Conclusion
Integrating synergistic biomarkers with serum metabolomics enhances early detection of DKD, potentially improving outcomes by slowing disease progression in T2DM patients.

Guideline/Statement/Fact Sheet
Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society: Jong Han Choi, SuJin Song, Soo Kyoung Kim, Jae Won Cho, Jae Hyun Bae, Shinje Moon, Jeong Hyun Lim, YeonHee Lee, Ji-Yun Hwang, YoonJu Song, Sang Soo Kim; Diabetes Metab J. 2026;50(1):32-46. Published online January 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.0848

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Background
Excess intake of added sugars contributes to obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and premature mortality. Sugar-sweetened beverages (SSBs), the main source of added sugars, are consistently linked to adverse outcomes. Artificially sweetened beverages (ASBs) have been suggested as short-term substitutes, but evidence regarding benefits and harms remains inconclusive, and guidance is lacking.
Methods
This consensus statement draws on a structured evidence review combining two approaches: an updated meta-analysis of randomized controlled trials (RCTs) assessing short- to intermediate-term effects of replacing SSBs with ASBs on weight and metabolic outcomes; and an umbrella review of systematic reviews of cohort studies evaluating long-term associations of SSBs and ASBs with major outcomes, including mortality, CVD, and T2DM.
Results
In 14 RCTs (3–76 weeks), replacing SSBs with ASBs produced modest reductions in body weight (–0.73 kg) and body fat (–0.72%), with inconsistent effects on glycemic and cardiometabolic markers. Evidence from 20 systematic reviews of cohorts (up to 34 years follow-up) showed that higher intake of both SSBs and ASBs was associated with increased risks of T2DM, CVD, and mortality, with relative risks for ASBs similar to those for SSBs.
Conclusion
ASBs may serve as a short-term substitution for individuals with high SSB intake, particularly those at elevated metabolic risk. However, regular or long-term use is not recommended due to uncertain safety and potential reinforcement of sweet preference. Public health strategies should emphasize reducing both SSBs and ASBs, prioritizing water and unsweetened beverages as the ultimate goal.

Citations

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Do Not Replace Your Sugar, Simply Eat Less!
Jeehyun Lee, Sunghwan Suh
Diabetes & Metabolism Journal.2026; 50(1): 30. CrossRef

Others
Efficacy and Safety of HD-6277, a Novel G Protein-Coupled Receptor 40 Agonist, in Individuals with Type 2 Diabetes Mellitus: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Clinical Trial: Yong-ho Lee, Kyung Wan Min, Jun Hwa Hong, Soo Lim, Jae Myung Yu, Choon Hee Chung, Jun Sung Moon, Jong Chul Won, Chul Woo Ahn, Jie-Eun Lee, Tae Nyun Kim, Byung-Wan Lee; Received July 17, 2025 Accepted October 11, 2025 Published online December 19, 2025; DOI: https://doi.org/10.4093/dmj.2025.0528 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study assessed the efficacy and safety of HD-6277, a novel oral G protein-coupled receptor 40 (GPR40) agonist in adults with inadequate control of type 2 diabetes mellitus (T2DM).
Methods
This double-blind, randomized, placebo-controlled phase 2 trial recruited 112 individuals aged 18–75 years with T2DM and glycosylated hemoglobin (HbA1c) levels between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks before screening. Parallel-group randomized trials of HD-6277 (50 and 100 mg groups vs. placebo) were conducted for 12 weeks. The primary outcome was the change in HbA1c levels from baseline to week 12. Secondary outcomes included changes in HbA1c, fasting plasma glucose (FPG), postprandial glucose, insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12.
Results
At week 12, HD-6277 at 50 and 100 mg demonstrated statistically significant reductions in HbA1c compared to placebo, with least square (LS) mean differences of –0.73% (95% confidence interval [CI], –1.11 to –0.35; P=0.0002) and –0.85% (95% CI, –1.21 to –0.50; P<0.0001), respectively. Both doses also produced clinically meaningful reductions in FPG. Additionally, HD- 6277 at 100 mg significantly increased the insulinogenic index compared to placebo, with an LS mean difference of 1.91 (95% CI, 0.34 to 3.48; P=0.0175). No clinically relevant treatment-related adverse events were observed.
Conclusion
HD-6277 at 50 and 100 mg improved glycemic control and was well-tolerated in adults with T2DM inadequately managed with diet and exercise. GPR40 agonists may offer a promising new therapeutic option for T2DM.

Pharmacotherapy
Efficacy and Safety of Enavogliflozin as Add-on in Adults with Type 2 Diabetes Mellitus Inadequately Controlled with Insulin or Insulin with Other Antidiabetic Drugs: Jun Hwa Hong, Kyung Wan Min, Chang Beom Lee, Parinya Chamnan, Thanitha Sirirak, Kiran Sony, Sarinya Sattanon, Hae Jin Kim, Sang-Yong Kim, Younghee Kim, Jung A Heo, Jae Min Cho, Jae Jin Nah, Mi Hee Park, Jae Hyeon Kim; Received May 30, 2025 Accepted October 14, 2025 Published online December 15, 2025; DOI: https://doi.org/10.4093/dmj.2025.0477 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The study evaluated the efficacy and safety of enavogliflozin, a novel, promising selective sodium-glucose cotransporter 2 inhibitor, as an add-on in adults with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin alone or combined with other antidiabetic drugs (OADs).
Methods
The double-blind, placebo-controlled, multicenter trial was conducted in South Korea and Thailand. Individuals with glycosylated hemoglobin (HbA1c) ≥7.5% after ≥8-week treatment with background insulin alone or combined with ≤2 OADs were randomized to receive enavogliflozin 0.3 mg or placebo (n=116 each) for 24 weeks. The primary outcome was a change in HbA1c at week 24. Secondary outcomes included, among others, changes in body weight, blood pressure, and other measures of glycemic control. Adverse events (AEs) were investigated throughout the study (Clinical trial registration number: NCT05466643).
Results
At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was –0.9% (P<0.001). Also, placebo-adjusted mean changes in fasting plasma glucose (–32.4 mg/dL, P<0.001), body weight (–1.3 kg, P<0.001), and total daily dose of insulin (–1.3 units, P=0.010) at week 24 were statistically significant. In addition, a significant decrease in blood pressure and fasting C-peptide was observed in the enavogliflozin group, along with a significant increase in homeostasis model assessment of β-cell function, yet without a concomitant change in homeostasis model assessment of insulinresistance. No significant increase in treatment-related AEs was observed for enavogliflozin.
Conclusion
Enavogliflozin 0.3 mg/day is an efficacious and safe add-on treatment option in T2DM patients controlled inadequately with insulin alone or combined with OADs.

Genetics
Evaluation of Sex-Stratified Polygenic Risk Scores for Type 2 Diabetes Mellitus and Glycemic Traits in the Framingham Heart Study: Ningyuan Wang, Yixin Zhang, Philip Schroeder, Alicia Huerta-Chagoya, Ravi Mandla, James B. Meigs, Alisa K. Manning, Ching-Ti Liu, Josée Dupuis, Josep M. Mercader; Received June 25, 2025 Accepted October 14, 2025 Published online December 9, 2025; DOI: https://doi.org/10.4093/dmj.2025.0557 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetes is a multifactorial disease with significant genetic predisposition. Polygenic risk scores (PRS) have been developed to estimate an individual’s genetic risk of a disease. Traditionally, PRS utilize sex-combined genome-wide association studies (GWAS) due to the limited availability of sex-stratified summary statistics. This study explores sex-dimorphic genetic effects and evaluates the potential benefits of incorporating sex-stratified effects in PRS for type 2 diabetes mellitus (T2DM) and glycemic traits by comparing PRS performance derived from sex-combined versus sex-stratified GWAS.
Methods
We performed a sex-heterogeneity test across sex-specific GWAS and identified nine signals with sex-dimorphic effects for T2DM. PRS[sex-combined] and PRS[sex-stratified] were developed using sex-combined and sex-stratified GWAS results for T2DM (41,444 cases and 354,539 controls), fasting glucose (n=120,595) and fasting insulin (n=98,210). We evaluated these PRS models in 8,379 participants (1,303 cases and 7,076 controls) from the Framingham Heart Study not included in the PRS derivation.
Results
Our findings suggest that sex-combined PRS currently offer better predictive performance for T2DM and glycemic traits.
Conclusion
These results highlight the need for larger sex-stratified studies and the optimization of sex-stratified risk models for clinical practice.

Lifestyle and Behavioral Interventions
Risk Determinants of Type 2 Diabetes Mellitus with Severe Obesity and Prediction Model for Diabetes Remission after Bariatric Metabolic Surgery: Zilong Wu, Yuxia Li, Dehui Wang, Bing Wu, Kaisheng Yuan, Yun Liu, Hao Zhu, Sijie Chen, Wah Yang, Ruixiang Hu, Cunchuan Wang; Diabetes Metab J. 2026;50(2):368-384. Published online November 25, 2025; DOI: https://doi.org/10.4093/dmj.2025.0337

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Abstract PDF Supplementary Material PubReader ePub: Background
Bariatric metabolic surgery (BMS) has been established as an effective intervention for obesity and type 2 diabetes mellitus (T2DM). However, systematic research addressing the onset of diabetes and post-surgical remission in severely obese populations remains scarce. This study aims to identify risk factors for T2DM in populations with severe obesity undergoing BMS and develop and validate a prediction model for the primary outcome of diabetes remission (DR) 1 year after BMS. This research provides a precise tool for managing T2DM in populations with severe obesity.
Methods
This research utilizes the China Obesity and Metabolic Surgery Database, retrospectively analyzing 3,670 severely obese populations who underwent BMS between January 2014 and January 2024. Differential analysis identified risk factors for T2DM onset, while univariate and multivariate regression analyses identified independent risk factors for DR post-surgery. A prediction model for DR was developed and internally validated.
Results
Factors associated with T2DM onset in severely obese populations included family history of diabetes, hypertension, hyperlipidemia, glycosylated hemoglobin (HbA1c) levels, and fasting plasma glucose. Independent factors influencing DR postsurgery included diabetes duration, surgical method, HbA1c, and insulin requirement. Subsequent model validation confirmed stable performance metrics (area under the curve values training, 0.71; validation, 0.72).
Conclusion
This study identifies risk factors for T2DM onset and a prediction model for DR following BMS in the Chinese severely obese population. It provides a more precise risk assessment tool for patients with severe obesity and T2DM, and lays the groundwork for future multicenter studies and international collaborations.

Pharmacotherapy
Glycemic Improvement with Low-Dose Dulaglutide Is Associated with Leptin and Obestatin Modulation in Type 2 Diabetes Mellitus: Inha Jung, Hangseok Choi, In Young Choi, Hyun Joo Cho, So Young Park, Da Young Lee, Ji A Seo, Nan Hee Kim, Ji Hee Yu; Received July 28, 2025 Accepted September 23, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0681 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control through insulinotropic and anorectic effects. However, the role of adipokines and appetite-related hormones in mediating the glycemic response remains unclear. This study evaluated changes in abdominal fat, food cravings, and circulating adipokines and gut hormones following dulaglutide treatment and identified predictors of glycemic improvement in type 2 diabetes mellitus (T2DM).
Methods
In this 24-week prospective observational study, 82 patients with T2DM and glycosylated hemoglobin (HbA1c) levels ≥7.0% despite standard therapy received dulaglutide 0.75 mg once weekly. Abdominal computed tomography, the General Food Cravings Questionnaire-Trait, and fasting levels of leptin, adiponectin, obestatin, ghrelin, and resistin were assessed at baseline and week 24. Glycemic responders were defined as those with an HbA1c reduction ≥0.5% and/or HbA1c <7.0% at 24 weeks. Multivariable regression analysis was performed to identify the factors associated with glycemic improvement.
Results
Among the 67 patients who completed the study, dulaglutide significantly reduced HbA1c, food cravings, leptin, and adiponectin levels. Obestatin levels increased modestly. Responders showed greater improvement in β-cell function and more pronounced reductions in food cravings. In the adjusted models, a decrease in leptin and an increase in obestatin were independently associated with HbA1c reduction, while decreased adiponectin was associated with poorer glycemic outcomes. Changes in body mass index or abdominal fat were not associated with glycemic improvement.
Conclusion
Dulaglutide improved glycemic control through mechanisms beyond weight reduction. Hormonal changes in leptin, adiponectin, and obestatin may help predict responses to GLP-1 RAs therapy.

Basic and Translational Research
Targeting PGC-1α by miRNA-374 Simultaneously Improve β-Cell Dysfunction and Suppress Hepatic Glucose Overproduction: Ji-Won Kim, Joonyub Lee, Young-Hye You, Chan-Hee Oh, Heon-Seok Park, Eun Young Lee, Seung-Hwan Lee, Seung-Hyun Ko, Ji-Ho Park, Kun-Ho Yoon; Received April 5, 2025 Accepted August 24, 2025 Published online November 3, 2025; DOI: https://doi.org/10.4093/dmj.2025.0287 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
In this study, we aimed to validate the potential of miR-374 in ameliorating hyperglycemia by regulating peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression in pancreatic islets and liver.
Methods
To identify miRNAs targeting PGC-1α, we performed miRNA chip analysis in rat islets under hyperglycemic and euglycemic conditions. Luciferase reporter assay was performed to identify miR binding sites in the 3’-untranslated region (3’ UTR) of PGC-1α. In db/db mice, miRNA-encapsulated adenoviruses were administered and intraperitoneal glucose tolerance test and glucose stimulated insulin secretion tests were performed. For enhanced delivery to β-cells, we developed exendin-4 (Ex-4) coated cationic lipoparticles (CCLs) encapsulating miRNAs. The therapeutic potential of Ex-4-CCL-miRNA was further evaluated in insulin-producing cells derived from induced pluripotent stem cells.
Results
By analyzing miRNA expression in primary rat islets exposed under hyperglycemic environment, we identified miR-374 as a potential target. In vitro experiments confirmed that miR-374 significantly suppressed PGC-1α expression in β-cells and hepatocytes by binding to its 3’-UTR. In vivo experiments using adenovirus-mediated miR-374 (Ad-miR-374) delivering directly to the pancreas and liver of db/db mice demonstrated improved glycemic control, enhanced insulin secretion, and downregulated hepatic gluconeogenesis-related genes (G6Pase, Pepck, PC). To enhance the clinical applicability of miR-374, we developed Ex-4-CCLs. Ex-4-CCL-miR-374 successfully alleviated hyperglycemia, restored pancreatic islet function, and decreased gluconeogenesis gene expression in db/db mice. Furthermore, Ex-4-CCL-miR-374 improved insulin secretory function in glucotoxicity-exposed human induced pluripotent stem cell-derived insulin producing cells.
Conclusion
Based on these findings, we propose that Ex-4-CCL-miR-374 as a promising therapeutic approach to reverse β-cell dysfunction and improve hepatic insulin resistance in type 2 diabetes mellitus.

Genetics
Elucidating the Epigenetic Landscape of Type 2 Diabetes Mellitus: A Multi-Omics Analysis Revealing Novel CpG Sites and Their Association with Cardiometabolic Traits: Ren-Hua Chung, Chun-Chao Wang, Djeane Debora Onthoni, Ben-Yang Liao, Tzu-Sheng Hsu, Eden R. Martin, Chao A. Hsiung, Wayne Huey-Herng Sheu, Hung-Yi Chiou; Diabetes Metab J. 2026;50(1):153-164. Published online October 28, 2025; DOI: https://doi.org/10.4093/dmj.2025.0041

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Background
Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles.
Methods
We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM.
Results
We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation.
Conclusion
Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Citations

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Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues
Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J. Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M. Mercader, Jason Flannick, James B.
Nature Metabolism.2026; 8(2): 506. CrossRef

Pharmacotherapy
Efficacy and Safety of High-Dose Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial: Jun Hwa Hong, Kyung Ah Han, You-Cheol Hwang, Eun-Gyoung Hong, Hae Jin Kim, Chang Beom Lee, Ho Chan Cho, Jong Chul Won, Hun-Sung Kim, Eui-Hyun Kim, Gwanpyo Koh, Kwang Hyun Ahn, Kyong Soo Park; Diabetes Metab J. 2026;50(2):320-330. Published online October 28, 2025; DOI: https://doi.org/10.4093/dmj.2024.0696

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the efficacy and safety of pioglitazone 30 mg/day add-on to inadequately controlled type 2 diabetes mellitus (T2DM) patients with treatment of dapagliflozin and metformin.
Methods
In this multicenter (34 sites), double-blind, randomized, phase 3 study, patients with T2DM with an inadequately controlled glycosylated hemoglobin (HbA1c) over 7.0% to treatment with dapagliflozin (10 mg/day) and metformin (≥1,000 mg/day) were randomized to receive additional pioglitazone 30 mg/day (n=124) or placebo (n=122) for 24 weeks. The primary outcome was the mean change of HbA1c from baseline to 24 weeks treatment. The efficacy and safety were evaluated with open label extension period, switching placebo to pioglitazone 30 mg/day at 48 weeks (ClinicalTrials.gov identifier: NCT05296044).
Results
The HbA1c after 24 weeks treatment reduced from 7.8%±0.8% to 7.0%±0.6% (P<0.0001). The proportions of patients who achieved HbA1c less than 7.0% at 24 weeks were significantly higher in pioglitazone add-on group (51.61% in pioglitazone vs. 22.95% in placebo, P<0.0001), or less than 6.5% at 24 weeks (21.77% in pioglitazone vs. 2.46% in placebo, P<0.0001). Body weight gain was 2.0 kg at 24 weeks with pioglitazone 30 mg/day and –0.6 kg at 24 weeks with placebo.
Conclusion
Addition of pioglitazone 30 mg/day to T2DM patients who did not reach the target HbA1c (≤7%) with treatment of dapagliflozin 10 mg/day and metformin over 1,000 mg/day showed effective glucose lowering efficacy without significant hypoglycemia and good tolerability with low prevalence of edema in spite of modest weight gain.

Cardiovascular Risk/Epidemiology
Prognostic Impact of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Coronary Ischemia: A Retrospective Cohort Study: Haochen Xuan, Yik-Ming Hung, Ran Guo, Qingwen Ren, Jiayi Huang, Jingnan Zhang, Wenli Gu, Ho-Leung Chan, Gaozhen Cao, Run Wang, Calvin Ka-Lam Leung, Tongda Xu, Kai-Hang Yiu; Received March 11, 2025 Accepted July 22, 2025 Published online October 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0200 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Patients with type 2 diabetes mellitus (T2DM) and coronary ischemia face an exceptionally elevated risk, and the achievement of complete revascularization (CR) within this population could be challenging.
Methods
Patients with T2DM and coronary ischemia based on coronary angiography and retrospective angiographic fractional flow reserve analysis between 2014 and 2016 were included. The impact of the extent of revascularization on the improvement of endpoint events by sodium-glucose cotransporter 2 (SGLT2) inhibitors was analyzed. The primary study endpoint was major adverse cardiac events (MACE), while all-cause mortality served as secondary endpoints. Kaplan-Meier analysis and Cox proportional hazards regression model were adopted to assess the association between SGLT2 inhibitors and endpoint incidence.
Results
A total of 671 patients were identified. Among them, 206 (30.7%) were prescribed with SGLT2 inhibitors, while 484 (72.1%) achieved CR after the operation. During a mean 36-month follow-up, 100 MACE and 89 all-cause mortality were recorded. SGLT2 inhibitor users demonstrated lower rates of MACE (8.3% vs. 17.8%, P=0.002) and all-cause mortality (6.3% vs. 16.3%, P<0.001) compared to non-users. After adjusting for confounding factors in multivariable Cox analysis, the association between SGLT2 inhibitors and reduced MACE incidence remained consistent both in the CR and incomplete revascularization subgroups (hazard ratio [HR], 0.498; 95% confidence interval [CI], 0.246 to 0.938; P=0.040; and HR, 0.341; 95% CI, 0.123 to 0.805; P=0.023, respectively).
Conclusion
SGLT2 inhibitors were found to be associated with a reduced risk of 3-year MACE and all-cause mortality in patients with T2DM and coronary ischemia, regardless of extent of revascularization.

Reviews

Lifestyle and Behavioral Interventions
Clinically Practical and Affordable Lifestyle Modification to Prevent Diabetes Mellitus in Real Practice: Inji Lee, Minji Kang, Ji Hye Choi, Hyunjung Lim, Suk Chon; Diabetes Metab J. 2025;49(5):951-963. Published online September 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0675

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Abstract PDF PubReader ePub: As the prevalence of type 2 diabetes mellitus continues to rise, the development of effective and sustainable prevention strategies has become a critical public health priority. Evidence from large-scale randomized controlled trials has established that lifestyle modification (LSM) programs can substantially reduce the risk of diabetes in high-risk individuals. However, routine implementation is limited by high intensity, costs, and resource requirements. We summarize major prevention trials and their effectiveness, feasibility, and limitations. Building on these insights, we introduce the Korean Diabetes Prevention Study (KDPS) as a contextually tailored model for the Korean healthcare system. The KDPS-LSM program was designed to integrate cultural and clinical relevance with practical applicability, consisting of a 6-month intensive phase of structured nutrition and lifestyle education followed by a maintenance phase to support long-term adherence. To promote sustainable change, the program incorporates the ‘10 habit’ lifestyle messages, grounded in the transtheoretical model of behavior change, which are designed for easy implementation in daily life. This review underscores the importance of developing culturally appropriate LSM programs that balance effectiveness with feasibility, and suggests that the KDPS-LSM model could serve as a useful foundation for establishing practical diabetes prevention strategies within national healthcare systems.

Lifestyle and Behavioral Interventions
Management of Early-Onset Type 2 Diabetes in Adults: Current Evidence and Future Directions: Matthew J. Savage, Jonathan Goldney, Tommy Slater, Priscilla Sarkar, Jack A. Sargeant, Emma G. Wilmot, Melanie J. Davies; Diabetes Metab J. 2025;49(5):934-950. Published online September 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0561

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The global prevalence of early-onset type 2 diabetes (EOT2D) is rising rapidly. Adults with EOT2D represent a high-risk population characterised by increased rates of microvascular and macrovascular complications, adverse psychological wellbeing and psychiatric comorbidities such as depression, and premature mortality compared to those with later-onset type 2 diabetes mellitus. This emerging population faces unique challenges, including high levels of diabetes-related stigma, clinical inertia, and competing life demands, such as starting a family. This review synthesises current evidence on the clinical management of EOT2D. Key therapeutic targets include weight reduction, preservation of β-cell function, cardiometabolic risk management, and psychological support. Overall, there are few randomized controlled trials (RCTs) undertaken specifically in adults with EOT2D. However, we summarise early data from the few RCTs that do report outcomes specific in young adults, with bariatric surgery, tirzepatide and intensive lifestyle interventions emerging as particularly effective treatments. There is a strong rationale that technology-based inventions and structured education programs may prove to be effective treatments but data from RCTs is lacking. We provide broad recommendations for future research and clinical practice based on the current evidence. In conclusion, substantial further research is required to inform tailored, evidence-based guidelines and improve long-term outcomes in this underserved population.

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Identification of oral microbial biomarkers for prediabetes in young adults: A two-stage population-based study
Jiaqi Li, Guishao Tang, Zhiguo Xie, Lin Yang, Zhiguang Zhou, Keyu Guo
Diabetes Research and Clinical Practice.2026; 232: 113101. CrossRef

Original Articles

Others
The Concurrent Challenges of Sarcopenia and Frailty: A 5-Year Mortality Risk Evaluation in Geriatric Patients with Type 2 Diabetes Mellitus: Burcu Eren Cengiz, Nurhayat Tugra Ozer, Celil Barlas Cengiz, Yavuz Sultan Selim Akgul, Sibel Akın; Received January 30, 2025 Accepted June 12, 2025 Published online September 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0077 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Type 2 diabetes mellitus (T2DM) is common among older adults and may increase the risk of sarcopenia and frailty. This study evaluates the impact of sarcopenia and frailty on 5-year mortality in older adults with T2DM.
Methods
We assessed a cohort study of 447 adults with T2DM who were more than 60 years old. To follow the guidelines set by the European Working Group on Sarcopenia in Older People 2 (EWGSOP 2), we used bioelectrical impedance analysis to measure muscle mass and a handgrip dynamometer to measure muscle strength. We assessed frailty using the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight (FRAIL) Scale. We categorised the patients into four groups: isolated sarcopenic, isolated alone, both conditions (sarcopenia and frailty), or neither.
Results
The mean age of the patients was 69 years, with 71.6% female. Isolated sarcopenic was present in 11.0%, isolated frail in 22.4%, and sarcopenia and frailty in 9.8%. After adjusting for variables such as age, sex, comorbidities, activities of daily living, glycemic control, and nutritional status, sarcopenia and frailty were found to be significantly associated with an increased risk of 5-year mortality. Isolated frail also significantly predicted mortality (hazard ratio, 2.59; 95% confidence interval, 1.34 to 5.03; P=0.005).
Conclusion
Sarcopenia and frailty are significant predictors of increased mortality risk in older adults with T2DM. Sarcopenia and frailty pose the highest risk. Early identification and targeted interventions for these conditions in older T2DM patients are crucial to improving outcomes.

Complications
Comparison of Efficacy and Safety of Cilostazol/Extract of Ginkgo biloba vs. Aspirin in Carotid Atherosclerosis in Patients with Diabetes Mellitus: You-Cheol Hwang, Mi Kyung Kim, Jung Hwan Park, Han Mi Yun, Sang Yong Kim, Soo Lim; Diabetes Metab J. 2026;50(2):357-367. Published online August 13, 2025; DOI: https://doi.org/10.4093/dmj.2025.0146

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Background
We conducted a prospective, randomized study to evaluate the combination of cilostazol (CTZ) and extract of Ginkgo biloba (EGb) and compare it with aspirin for the prevention of atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM).
Methods
One hundred five patients with T2DM and increased carotid intima-media thickness (IMT) were randomly assigned to receive either CTZ 200 mg plus EGb 160 mg once daily or aspirin (ASA) 100 mg/day for 12 months. The primary endpoint was the change in maximum carotid IMT.
Results
The mean age and body mass index were 61.6±8.4 years and 25.2±3.1 kg/m² in the CTZ/EGb group and 61.6±7.6 years and 24.5±3.3 kg/m² in the ASA group, respectively. CTZ/EGb treatment reduced the maximum IMT in the bulb area (from 1.435±0.690 to 1.346±0.688 mm on the right; from 1.359±0.528 to 1.299±0.528 mm on the left), whereas ASA treatment did not, resulting in significant between-group differences (P<0.05). No significant differences were observed in the common carotid and internal carotid arteries. The CTZ/EGb group showed a reduction in triglycerides and an increase in high-density lipoprotein cholesterol levels. Additionally, aspartate and alanine aminotransferase levels decreased only in the CTZ/EGb group. There were no significant differences in Mini-Mental State Examination (MMSE) score changes or adverse events (ClinicalTrials.gov number: NCT05906199).
Conclusion
Twelve months of CTZ/EGb combination therapy significantly attenuated the progression of carotid atherosclerosis compared with aspirin in patients with T2DM.

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Cilostazol/Extract of Ginkgo biloba or Aspirin, What Is the Treatment in Atherosclerosis Prevention? (Diabetes Metab J 2026;50:357-67)
Christian Saleh, Ivanka Maduna, Hrvoje Budincevic
Diabetes & Metabolism Journal.2026; 50(2): 414. CrossRef
Comparison of Efficacy and Safety of Cilostazol/Extract of Ginkgo biloba vs. Aspirin in Carotid Atherosclerosis in Patients with Diabetes Mellitus (Diabetes Metab J 2026;50:357-67)
You-Cheol Hwang, Sang Yong Kim, Soo Lim
Diabetes & Metabolism Journal.2026; 50(2): 428. CrossRef

Genetics
SLC30A8 Rare Variant Modify Contribution of Common Genetic and Lifestyle Factors toward Type 2 Diabetes Mellitus: Hye-Mi Jang, Mi Yeong Hwang, Yi Seul Park, Bong-Jo Kim, Young Jin Kim; Diabetes Metab J. 2026;50(2):385-395. Published online August 13, 2025; DOI: https://doi.org/10.4093/dmj.2024.0830

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Background
This study aimed to investigate the modifying effects of rare genetic variants on the risk of type 2 diabetes mellitus (T2DM) in the context of common genetic and lifestyle factors.
Methods
We conducted a comprehensive analysis of genetic and lifestyle factors associated with T2DM in a cohort of 146,284 Korean individuals. Among them, 4,603 individuals developed T2DM during the follow-up period of up to 17 years. We calculated a polygenic risk score (PRS) for T2DM and identified carriers of the rare allele I349F at SLC30A8. A Healthy Lifestyle Score (HLS) was also derived from physical activity, obesity, smoking, diet, and sodium intake levels. Using Cox proportional hazards models, we analyzed how PRS, HLS, and I349F influenced T2DM incidence.
Results
Results showed that high PRS and poor lifestyle were associated with increased risk. Remarkably, I349F carriers exhibited a lower T2DM prevalence (5.7% compared to 11.7% in non-carriers) and reduced the impact of high PRS from 23.18% to 12.70%. This trend was consistent across different HLS categories, with I349F carriers displaying a lower risk of T2DM.
Conclusion
The integration of common and rare genetic variants with lifestyle factors enhanced T2DM predictability in the Korean population. Our findings highlight the critical role of rare genetic variants in risk assessments and suggest that standard PRS and HLS metrics alone may be inadequate for predicting T2DM risk among carriers of such variants.

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Personalised Nutrition in Obesity and Prediabetes: Do Genotypes Matter?
Magdalena Bossowska, Filip Bossowski, Edyta Adamska-Patruno, Katarzyna Maliszewska, Adam Krętowski
Nutrients.2026; 18(5): 815. CrossRef
Differential contributions of cardiovascular health-related lifestyle factors to epigenetic ageing: implications for healthy longevity
Da-eun Lee, Yi Seul Park, Hye-Mi Jang, Bong-Jo Kim, Young Jin Kim, Sung-il Cho, Kyeezu Kim
BMC Medicine.2025;[Epub] CrossRef

Cardiovascular Risk/Epidemiology
Associations of Cardiocerebrovascular Risks and Exercise according to Menopausal Status in Women with Type 2 Diabetes Mellitus: A Nationwide Cohort Study: Ji-Hee Ko, Sun Joon Moon, Kyung-Do Han, Hye-Mi Kwon, Se-Eun Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2026;50(1):101-114. Published online August 13, 2025; DOI: https://doi.org/10.4093/dmj.2024.0487

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Abstract PDF Supplementary Material PubReader ePub: Background
Menopausal status can increase the risk of cardiocerebrovascular diseases (CCVDs) in women with type 2 diabetes mellitus (T2DM). Regular exercise is well-known to reduce this risk. This study explored the impact of exercise on CCVD and mortality in women with T2DM according to their menopausal status.
Methods
A total of 32,477 premenopausal and 53,690 postmenopausal Korean women with T2DM aged 40 to 60 years from a national health examination cohort (2009 to 2018) were included. We evaluated risks for stroke, myocardial infarction (MI), and mortality based on exercise intensity. Cox proportional hazard regression analyses were performed to obtain the adjusted hazard ratio (aHR) and 95% confidence interval.
Results
Exercise reduced stroke, MI, and mortality risks in women with T2DM, regardless of menopausal status. The highest effects of aHR compared to the sedentary group were 0.68 for stroke, 0.66 for MI, and 0.81 for mortality. Postmenopausal women experienced significant MI risk reductions at most exercise intensities, with the greatest reduction in the ≥1,500 metabolic equivalent of task score group unlike premenopausal women. However, stroke and mortality risk reductions in postmenopausal women were less pronounced compared to premenopausal women.
Conclusion
Exercise reduces CCVD risk in women with T2DM across menopausal status. Postmenopausal women with T2DM had more benefits from exercise on MI but fewer benefits on stroke and mortality than premenopausal women. In premenopausal women with T2DM, exercise was not associated with a lower MI risk.

Pharmacotherapy
New Users of Sodium-Glucose Cotransporter 2 Inhibitors Are at Low Risk of Prostate Cancer: A Nationwide Cohort Study: Yun Kyung Cho, Sehee Kim, Myung Jin Kim, Woo Je Lee, Ye-Jee Kim, Chang Hee Jung; Diabetes Metab J. 2026;50(1):90-100. Published online July 22, 2025; DOI: https://doi.org/10.4093/dmj.2024.0693

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Background
Preclinical studies have reported anticancer properties of sodium-glucose cotransporter 2 inhibitors (SGLT2is). We aimed to elucidate the association between the use of SGLT2is and the risk of prostate cancer among male patients with type 2 diabetes mellitus (T2DM).
Methods
An active-comparator, new-user cohort design using a nationwide database between September 2014 and June 2020 was conducted on 45,601 new SGLT2i users and 205,395 new users of other glucose-lowering medications (oGLMs). In the following 1:1 propensity score matched (PSM) analysis, 35,371 SGLT2i users matched with an equivalent number of oGLM users were assessed. The hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer were calculated.
Results
Among the cohort, prostate cancer was diagnosed in 210 out of 45,601 SGLT2i users, corresponding to a cumulative incidence of 1.0%, in contrast to 1,880 cases among 205,395 users of oGLMs, with a cumulative incidence of 1.5%. The use of SGLT2is was significantly correlated with a reduced risk of prostate cancer based on a multivariable-adjusted HR of 0.83 (95% CI, 0.71 to 0.98). PSM analysis affirmed 18% reduction in prostate cancer risk associated with SGLT2i use (HR, 0.82; 95% CI, 0.67 to 0.99). Subgroup analyses revealed that body mass index (BMI) significantly influenced the effect of SGLT2i on prostate cancer risk, with a more pronounced reduction in the subgroup with a BMI <25 kg/m² (P=0.037).
Conclusion
The use of SGLT2is in Korean male patients with T2DM is associated with a lower risk of prostate cancer.

Citations

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Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents
Yun Kyung Cho, Chang Hee Jung
Diabetes & Metabolism Journal.2026; 50(1): 1. CrossRef

Review

Others
Differences between Type 2 Diabetes Mellitus and Obesity Management: Medical, Social, and Public Health Perspectives: Soo Lim, Ga Eun Nam, Arya M. Sharma; Diabetes Metab J. 2025;49(4):565-579. Published online June 11, 2025; DOI: https://doi.org/10.4093/dmj.2025.0278

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Obesity and type 2 diabetes mellitus (T2DM) are among the most urgent global public health challenges, yet differ markedly in recognition and management across medical, social, infrastructure, and policy domains. T2DM is supported by clear diagnostic criteria, defined treatment targets, and broad acceptance as a chronic disease. In contrast, obesity is assessed using imprecise metrics like body mass index, lacks standardized treatment goals, and is often misunderstood as a lifestyle issue rather than a chronic, relapsing disease. This misconception contributes to stigma, discrimination, and unrealistic patient expectations. T2DM receives substantial research funding, comprehensive clinical guidelines, and structured medical education, with strong support from large professional societies and multidisciplinary care models. Obesity care remains underfunded, inconsistently delivered, and underrepresented in medical training. Public health and policy efforts strongly favor T2DM, providing coordinated programs, insurance coverage, and regulatory oversight. Conversely, obesity is marginalized, with limited policy influence and a largely unregulated commercial weight-loss industry. Bridging these disparities requires adopting lessons from T2DM management—such as evidence-based guidelines, improved provider training, expanded insurance coverage, and public health strategies—to enhance obesity care and recognize it as a chronic disease requiring long-term, structured management.

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GLP-1 Receptor Agonists: Advances in Mechanism, Therapeutic Applications, and Future Perspectives
Megha Pawar, Chandrashekhar Patil, Zubershaha Fakir, Durgesh Pagar, Sunil Mahajan
BioMed Target Journal.2025; : 2. CrossRef

Original Articles

Metabolic Risk/Epidemiology
Ultra-Processed Food Intake and Risk of Type 2 Diabetes Mellitus: A Dose-Response Meta-Analysis of Prospective Studies: Yujin Kim, Yoonkyoung Cho, Jin Eui Kim, Dong Hoon Lee, Hannah Oh; Diabetes Metab J. 2025;49(5):1064-1074. Published online June 9, 2025; DOI: https://doi.org/10.4093/dmj.2024.0706; Correction in: Diabetes Metab J 2026;50(1):211

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Background
Although some studies suggest a positive association between ultra-processed food (UPF) intake and type 2 diabetes mellitus (T2DM), little is known about the exact shape and risks associated with different units (percentage of g/day, absolute g/day, serving/day) of UPF intake and whether the association is independent of diet quality, total energy intake, and body mass index (BMI).
Methods
Prospective studies published through January 2024 were identified by searching PubMed, Embase, and Web of Science. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models. A nonlinear dose-response meta-analysis was conducted using restricted cubic spline analysis.
Results
After screening 569 publications, a total of 12 prospective cohort studies were included. Comparing the highest vs. lowest categories of intake, summary RR for T2DM risk was 1.48 (95% CI, 1.36 to 1.61). Higher summary RRs were observed among studies from Europe and North America. Among individual UPF subgroups, processed meats (summary RR, 1.34; 95% CI, 1.16 to 1.54) were positively associated, whereas ultra-processed cereals and breads (0.98; 95% CI, 0.97 to 0.99) and packaged savory snacks (0.92; 95% CI, 0.88 to 0.95) were inversely associated. The summary RRs associated with every 10% (of g/day), 100-g/day, and 1-serving/day increase in UPF intake were 1.14 (95% CI, 1.11 to 1.17), 1.05 (95% CI, 1.03 to 1.06), and 1.04 (95% CI, 1.03 to 1.05), respectively. The dose-response curve for absolute g/d intake suggested nonlinearity, showing a steeper risk increase approximately at >300 g/day. The associations persisted after adjustment for diet quality, energy intake, or BMI.
Conclusion
Our data suggest that UPF intake increases diabetes risk, with a potential threshold effect at 300 g/day.

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Ultra-Processed Food Intake and Risk of Type 2 Diabetes Mellitus: A Dose-Response Meta-Analysis of Prospective Studies (Diabetes Metab J 2025;49:1064-74)
Lirong Hu, Aiji Chen, Gang Tian
Diabetes & Metabolism Journal.2026; 50(1): 194. CrossRef
Ultra-Processed Food Intake and Risk of Type 2 Diabetes Mellitus: A Dose-Response Meta-Analysis of Prospective Studies (Diabetes Metab J 2025;49:1064-74)
Yujin Kim, Hannah Oh
Diabetes & Metabolism Journal.2026; 50(1): 208. CrossRef
Trends in sales of sugar-sweetened beverages and associated type 2 diabetes burden in nine African countries: an ecological time-series analysis
Caroline H. Karugu, Gershim Asiki, Senzo Mthembu, Samuel Iddi, Peter M. Kaberia, Shukri F. Mohamed, Richard E. Sanya, Sylvia Kiwuwa-Muyingo, Stefanie Vandevijvere, Charles Agyemang
Global Health Action.2025;[Epub] CrossRef

Basic and Translational Research
Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and α-Glucosidase in a Type 2 Diabetes Mellitus Animal Model: Serin Hong, Byung Soo Kong, Hyunsuk Lee, Young Min Cho; Diabetes Metab J. 2025;49(6):1229-1241. Published online May 22, 2025; DOI: https://doi.org/10.4093/dmj.2024.0339

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Background
The prevalence of type 2 diabetes mellitus (T2DM) increases with age, and cellular senescence of pancreatic β-cells plays a key role in T2DM pathogenesis. As canagliflozin and acarbose have been shown to increase lifespan in mice, we investigated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, α-glucosidase inhibitor or both on the cellular senescence of β-cells in a T2DM mouse model.
Methods
Enavogliflozin (0.3 mg/kg), acarbose (10 mg/kg), or vehicle was orally administered daily to db/db mice for 6 weeks. The levels of senescence markers (p16, p21, and p53) in the pancreas and kidney were measured through real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot. In an in vitro analysis, isolated pancreatic islets were exposed to H₂O₂ to induce cellular senescence, then treated with β-hydroxybutyrate (β-HB), and subsequently assessed for levels of senescent markers.
Results
Enavogliflozin alone or combined with acarbose effectively lowered blood glucose levels in db/db mice. The combined treatment resulted in the greatest increase in β-cell function calculated using insulinogenic index and homeostasis model assessment of β-cell function compared to the vehicle. Additionally, the combined treatment significantly reversed the increase in p16, with a similar trend observed in p21 and p53 in the islets. Treatment increased circulating β-HB and in vitro analysis suggested the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by β-HB in reducing senescence in the islets.
Conclusion
The combined administration of enavogliflozin and acarbose significantly reduced blood glucose, improved β-cell function, and reduced senescent β-cells in db/db mice. This combination therapy holds potential as a senotherapeutic strategy for managing T2DM.

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Microneedle strategies for diabetic wound management: A comprehensive review of materials, mechanisms, and therapeutic outcomes
Kaustubh Naik, Kanhaiya Singh
Materials Today Advances.2026; 29: 100684. CrossRef

Metabolic Risk/Epidemiology
Beta-Cell Function, Insulin Sensitivity, and Metabolic Characteristics in Young-Onset Type 2 Diabetes Mellitus: Findings from Anam Diabetes Observational Study: Ji Yoon Kim, Jiyoon Lee, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2025;49(6):1287-1297. Published online May 21, 2025; DOI: https://doi.org/10.4093/dmj.2024.0601

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Abstract PDF Supplementary Material PubReader ePub: Background
In this study, we aimed to determine the metabolic characteristics and changes in the early stages of young-onset type 2 diabetes mellitus (YOD) in Koreans.
Methods
From the Anam Diabetes Observational Study cohort (2017–2023), the characteristics of newly diagnosed YOD (<40 years of age, n=39) and later-onset (≥40 years of age) type 2 diabetes mellitus (LOD, n=178) were compared at diagnosis and 1 year later. All participants underwent an oral glucose tolerance test at diagnosis and annually thereafter. β-Cell function was determined using the disposition index (DI), calculated as the insulinogenic index×Matsuda insulin sensitivity index (ISI). Insulin sensitivity was determined using ISI and homeostasis model assessment of insulin resistance (HOMA2-IR).
Results
Mean (±standard deviation) age of individuals with YOD was 29.8±6.4 years, and 76.9% were male. YOD patients had higher body mass index (29.8 kg/m² vs. 27.2 kg/m², P=0.020), fat mass (30.5 kg vs. 24.1 kg, P=0.011), fatty liver index (65.4 vs. 49.2, P=0.005), and glycosylated hemoglobin (HbA1c) level at diagnosis (9.3% vs. 7.7%, P<0.001) compared with LOD patients. YOD patients exhibited lower insulin sensitivity (ISI: 2.79 vs. 3.26, P=0.008; HOMA2-IR: 2.72 vs. 1.83, P<0.001) and β-cell function (DI) at diagnosis (0.41 vs. 0.72, P=0.003) than LOD patients. Following 1 year of treatment, DI improved by 94% in YOD along with improvement in HbA1c; however, it was still significantly lower than that of LOD (0.64 vs. 0.90, P=0.017).
Conclusion
Individuals with YOD have unfavorable metabolic characteristics, substantially reduced insulin sensitivity, and decompensated β-cell function at disease onset, which persist even after treatment.

Complications
Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study: Eun Roh, Ji Hye Heo, Han Na Jung, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm; Diabetes Metab J. 2025;49(5):1106-1115. Published online May 21, 2025; DOI: https://doi.org/10.4093/dmj.2024.0406

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Background
Remnant cholesterol (remnant-C) has been linked to the risk of various vascular diseases, but the association between remnant-C and end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) remains unclear.
Methods
Using a nationwide cohort, a total of 2,537,149 patients with T2DM without ESRD, who had participated in the national health screening in 2009, were enrolled and followed up until 2020. Low-density lipoprotein cholesterol (LDL-C) levels were assessed by the Martin-Hopkins method, and remnant-C was calculated as total cholesterol–LDL-C–high-density lipoprotein cholesterol.
Results
During a median follow-up period of 10.3 years, 26,246 patients with T2DM (1.03%) developed ESRD. Participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.12 (95% confidence interval [CI], 1.08 to 1.17), 1.20 (95% CI, 1.15 to 1.24), and 1.33 (95% CI, 1.26 to 1.41) in the second, third, and fourth quartile, compared with the lowest quartile, in multivariable-adjusted analyses. The positive association between remnant-C and ESRD remained consistent, irrespective of age, sex, presence of pre-existing comorbidities, and use of anti-dyslipidemic medications. The increased risk of ESRD was more pronounced in high-risk subgroups, including those with hypertension, chronic kidney disease, obesity, and a longer duration of diabetes.
Conclusion
These findings suggest that remnant-C profiles in T2DM have a predictive role for future progression of ESRD, independent of traditional risk factors for renal dysfunction.

Citations

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Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2025;49:1106-15)
Jun Hwa Hong
Diabetes & Metabolism Journal.2026; 50(1): 190. CrossRef
A Narrative Review of Remnant Cholesterol as an Independent Atherogenic Lipoprotein in Type 2 Diabetes: Pathophysiology and Clinical Implications
Ramdhani Natsir, Eli Halimah, Ajeng Diantini, Jutti Levita
Therapeutics and Clinical Risk Management.2026; Volume 22: 1. CrossRef

Metabolic Risk/Epidemiology
Predictive Models for Type 2 Diabetes Mellitus in Han Chinese with Insights into Cross-Population Applicability and Demographic Specific Risk Factors: Ying-Erh Chen, Djeane Debora Onthoni, Shao-Yuan Chuang, Guo-Hung Li, Yong-Sheng Zhuang, Hung-Yi Chiou, Wayne Huey-Herng Sheu, Ren-Hua Chung; Diabetes Metab J. 2025;49(6):1272-1286. Published online May 21, 2025; DOI: https://doi.org/10.4093/dmj.2024.0319

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Background
The rising global incidence of type 2 diabetes mellitus (T2DM) underscores the need for predictive models that enhance early detection and prevention across diverse populations. This study aimed to identify predictors of incident T2DM within a Han Chinese population, assess their impact across various age and sex demographics, and explore their applicability to European populations.
Methods
Using data from about 65,000 participants in the Taiwan Biobank (TWB), we developed a predictive model, achieving an area under the receiver operating characteristic curve of 90.58%. Key predictors were identified through LASSO regression within the TWB cohort and validated using over 4 million records from Taiwan’s Adult Preventive Healthcare Services (APHS) program and the UK Biobank (UKB).
Results
Our analysis highlighted 13 significant predictors, including established factors like glycosylated hemoglobin (HbA1c) and blood glucose levels, and less conventionally considered variables such as peak expiratory flow. Notable differences in the effects of HbA1c levels and polygenic risk scores between the TWB and UKB cohorts were observed. Additionally, age and sex-specific impacts of these predictors, detailed through APHS data, revealed significant variances; for instance, waist circumference and diagnosed mixed hyperlipidemia showed greater impacts in younger females than in males, while effects remained uniform across male age groups.
Conclusion
Our findings offer novel insights into the diagnosis and management of diabetes for the Han Chinese and potentially for broader East Asian populations, highlighting the importance of ethnic and demographic diversity in developing predictive models for early detection and personalized intervention strategies.

Citations

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The Relationship Between High-Density Lipoprotein (HDL) and Glycated Hemoglobin (HbA1C) in Type 2 Diabetes Mellitus Patients: Implications for Cardiovascular Risk
Setyoadi Setyoadi, Dina Dewi Sartika Lestari Ismail, Annisa Wuri Kartika, Dewi Purnama Sari, Angel Dwi Septian, Adelina Stefanie Lallo, Rara Kurniasari
Journal of Rural Community Nursing Practice.2025; 3(2): 234. CrossRef

Review

Basic and Translational Research
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies: Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi; Diabetes Metab J. 2025;49(3):333-347. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0106

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

Citations

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Original Articles

Pharmacotherapy
Initial Pharmacological Strategies in People with Early Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis: Jong Han Choi, Bo Kyung Koo, Ye Seul Yang, Se Hee Min, Jong Suk Park, Sang Youl Rhee, Hyun Jung Kim, Min Kyong Moon; Diabetes Metab J. 2025;49(6):1252-1261. Published online April 29, 2025; DOI: https://doi.org/10.4093/dmj.2024.0660

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Background
Type 2 diabetes mellitus (T2DM) requires stringent glycemic control from an early stage to prevent complications. The most effective treatment regimen for early T2DM remains unclear. The study aimed to compare the efficacy and safety of monotherapies and combination therapies for early T2DM.
Methods
A systematic review and network meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials focused on glycemic control, body weight, and adverse events were included. The primary outcomes were changes in glycosylated hemoglobin (HbA1c) and odds of achieving the target HbA1c after 6 months.
Results
All combination therapies were more effective than monotherapy. Metformin+glucagon-like peptide-1 receptor agonists (GLP-1RA) (weighted mean difference [WMD] –1.50%; 95% confidence interval [CI] –2.04 to –0.96) and metformin+dipeptidyl peptidase-4 inhibitors (WMD –1.46%; 95% CI, –1.96 to –0.95) were the most effective for change in HbA1c. GLP-1RA and sodium- glucose cotransporter-2 inhibitors led to weight reduction. Apart from the increased risk of hypoglycemia with sulfonylureas, no significant differences in adverse events were observed across regimens.
Conclusion
Early combination therapy effectively improved glycemic control in patients with early T2DM without significantly increasing adverse risks. Future studies should explore new combinations, including potent GLP-1RA.

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LASSBio-1986 as a Multifunctional Antidiabetic Lead: SGLT1/2 Docking, Redox–Inflammatory Modulation and Metabolic Benefits in C57BL/6 Mice
Landerson Lopes Pereira, Raimundo Rigoberto B. Xavier Filho, Gabriela Araújo Freire, Caio Bruno Rodrigues Martins, Maurício Gabriel Barros Perote, Cibelly Loryn Martins Campos, Manuel Carlos Serrazul Monteiro, Isabelle de Fátima Vieira Camelo Maia, Renata
International Journal of Molecular Sciences.2026; 27(2): 829. CrossRef

Others
Fibroblast Growth Factor 21 Levels Are Associated With Perception and Neural Responses to Sweetness in Type 2 Diabetes Mellitus: Piao Kang, Ying Zhang, Dian Zeng, Dan Liu, Rui Han, Yuwei Lu, Di Cheng, Qinyi Wang, Silin Liu, Liang Wu, Qian Wu, Shujie Yu, Anran Chen, Jingyi Guo, Wenli Ge, Jiacheng Ni, Jingyi Yang, Xiaomeng Wu, Lifei Ma, Weiping Jia, Qichen Fang, Yuehua Li, Huating Li; Diabetes Metab J. 2025;49(4):893-905. Published online March 26, 2025; DOI: https://doi.org/10.4093/dmj.2024.0390

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Background
The relationship between fibroblast growth factor 21 (FGF21) and sweet taste perception and preference in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to investigate this relationship and examine the neural responses of T2DM patients to high-calorie sweet (HCS) food pictures, further exploring its correlation with FGF21 levels.
Methods
We assessed sweet taste perception and preference in 40 T2DM patients and 41 controls using classical scales. Subsequently, the neural responses of 11 T2DM patients and 11 controls to HCS pictures were examined using functional magnetic resonance imaging. FGF21 levels were measured using chemiluminescent immunoassay, and the correlations with taste perception and neural responses were analyzed.
Results
Increased FGF21 levels were associated with decreased sweet perception and increased sweet taste preference in T2DM patients. Compared to control, T2DM patients exhibited greater neural activations in the orbitofrontal cortex, anterior cingulate cortex (ACC), thalamus, and hippocampus (HCS vs. non-food) as well as the putamen (HCS vs. low-calorie food). Notable differences were observed in the parahippocampal gyrus, insula, ACC, and hippocampus in T2DM patients (HCS vs. high-calorie non-sweet). Additionally, FGF21 accounted for 30.39% and 32.4% of the associations between T2DM and ACC, and parahippocampal gyrus, respectively.
Conclusion
FGF21 levels were independently associated with changes in sweet taste perception and preference in T2DM patients and were significantly associated with activation in reward-related brain regions. This study reveals the potential role of FGF21 in regulating responses to sweet foods in T2DM and provides insight to develop new therapeutic strategies for diabetes.

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Exploring Biomarkers in Type 2 Diabetes Mellitus versus Normoglycemia Identified through High-Throughput Proteomics: A Systematic Review and Meta-Analysis
Julia García-Currás, Raquel Pérez-Lois, Guillermo L. Taboada, María P. Pata
Journal of Proteome Research.2026; 25(1): 4. CrossRef

Complications
Global, Regional, and National Temporal Trends in Incidence for Type 2 Diabetes Mellitus Related Chronic Kidney Disease from 1992 to 2021: Yu Cao, Huiting Chen, Hui Liu, Hao Wu, Wei Gao; Diabetes Metab J. 2025;49(4):848-861. Published online March 11, 2025; DOI: https://doi.org/10.4093/dmj.2024.0593

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Background
Type 2 diabetes mellitus (T2DM) is a major cause of declining renal function.
Methods
Temporal trends in T2DM-related chronic kidney disease (CKD-T2DM) incidence across 204 countries and territories from 1992 to 2021 were analyzed using data from the Global Burden of Disease 2021. The impact of macro-factors (demographic change, age, period, and birth cohort) on CKD-T2DM incidence trends was assessed using decomposition analyses and age-period- cohort modeling, highlighting opportunities to improve incidence and reduce regional disparities.
Results
In 2021, global CKD-T2DM incidence cases reached 2.01 million, a 150.92% increase since 1992, with population growth and aging contributing to 80% of this rise. The age-standardized incidence rate (ASIR) ranged from 15.09 per 100,000 in low sociodemographic index (SDI) regions to 23.07 in high SDI regions. China, India, the United States, and Japan have the most incidence cases, accounted for 69% of incidence cases globally. With 175 countries showing an increasing ASIR trend. Unfavorable trend in ASIR increase were generally found in most high-middle and middle SDI countries, such as China and Mexico (net drift=0.15% and 1.17%, per year). Age-period-cohort analyses indicated a high incidence risk near age 80, with worsening risks for recent periods and birth cohorts, except in high SDI areas.
Conclusion
The CKD-T2DM incidence burden continues to rise globally, with significant variations between countries, posing major global health implications. CKD-T2DM is largely preventable and treatable, warranting greater attention in global health policy, particularly for older populations and in low and middle SDI regions.

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Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities
Jean-Michel Halimi, Laurent Fauchier, Alexandre Karras, Chloé Amouyal, Dominique Eladari, Patrick Rossignol, Gabriel Choukroun, Philippe Zaoui, Nicolas Girerd, Samy Hadjadj
European Journal of Preventive Cardiology.2026; 33(1): 8. CrossRef
Frailty and incident diabetes among middle-aged and older adults: Evidence from a large prospective cohort in China
Yingzhen Gu, Xiaorong Han, Jinxing Liu, Yifan Li, Wei Zhang, Naqiang Lv, Aimin Dang
Nutrition, Metabolism and Cardiovascular Diseases.2025; 35(10): 104114. CrossRef
Addressing Inequities in Early‐Onset Diabetic Kidney Failure in Australia: A Response to Ellis et al.
Gokhan Koker
Nephrology.2025;[Epub] CrossRef
An Overview of Sex-Based Differences in the Onset and Progression of DKD in the Well-Known Model, ZSF1 Rats
Arunita Chatterjee, Sharma S. Prabhakar
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Electroacupuncture ameliorates glycolipid metabolism disorder in skeletal muscle of type 2 diabetic rats via modulation of the AMPK/PGC-1α/TFAM signaling pathway
Fang Luo, Junjie Feng, Jumahan Nverjiang, Jiangnan Ye, Chang Liu, Hanhan Chen, Zhuoxuan Li, Qunwen Lu, Wei Zhang, Furong Zhang, Jun Zhu, Chengguo Su
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef

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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Background
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.

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Association between body weight time in target range and risk of type 2 diabetes in adults with obesity
Soojin Park, Seohyun Kim, Sang Ho Park, Minkyeong Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Gyuri Kim
Diabetology & Metabolic Syndrome.2026;[Epub] CrossRef
Association of temporal MASLD with type 2 diabetes, cardiovascular disease and mortality
Eugene Han, Kyung-Do Han, Yong-ho Lee, Kyung-Soo Kim, Sangmo Hong, Jung Hwan Park, Cheol-Young Park
Cardiovascular Diabetology.2025;[Epub] CrossRef
Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
Ji Yoon Kim, Nam Hoon Kim, Jiyoon Lee, Dong-Hoon Kim, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef
Young Adults at Risk: Tackling the Surge of Early‑Onset Type 2 Diabetes in Korea
Eun-Hee Cho
Endocrinology and Metabolism.2025; 40(4): 542. CrossRef
Young patients with type 2 diabetes have high relative risks for complications in a country with middle-high sociodemographic index, similarly to those countries with high index
Gergő A. Molnár, Zoltán Kiss, István Wittmann
Frontiers in Endocrinology.2025;[Epub] CrossRef
Cost-Effectiveness Analysis of Real-Time Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in People With Type 2 Diabetes Treated With Non-Intensive Insulin Therapy in South Korea
Ji Yoon Kim, Sabrina Ilham, Hamza Alshannaq, Richard F. Pollock, Martin Field, Gregory J. Norman, Sang-Man Jin, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2025;[Epub] CrossRef
Can screening for albuminuria detect type 2 diabetes mellitus?
Mi Kyung Kim
Kidney Research and Clinical Practice.2025; 44(6): 857. CrossRef
Association between severe acute pancreatitis and new-onset diabetes: a propensity score-matched real-world study
Djibril M. Ba, Phil A. Hart, Tian Qiu, Somashekar G. Krishna, Xiang Gao, Douglas L. Leslie, David Bradley, Jennifer Maranki, Kadiyatu Fofana, Vernon M. Chinchilli, Ariana R. Pichardo-Lowden
Frontiers in Endocrinology.2025;[Epub] CrossRef

Metabolic Risk/Epidemiology
Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study: Young-eun Kim, Min Heui Yu, Chung Mo Nam, Eun Seok Kang; Diabetes Metab J. 2025;49(2):252-263. Published online March 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0277

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Background
Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening.
Methods
A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk.
Results
The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01).
Conclusion
In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.

Citations

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Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study (Diabetes Metab J 2025;49:252-63)
Young-eun Kim, Min Heui Yu, Chung Mo Nam, Eun Seok Kang
Diabetes & Metabolism Journal.2025; 49(3): 522. CrossRef
Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63)
Shih-Wei Lai, Kuan-Fu Liao
Diabetes & Metabolism Journal.2025; 49(3): 518. CrossRef

Complications
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; Diabetes Metab J. 2025;49(3):485-497. Published online February 17, 2025; DOI: https://doi.org/10.4093/dmj.2024.0387

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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.

Citations

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Association Between Blood Glucose Variability and Clinical Outcomes in Patients With Sepsis: A Systematic Review and Meta‐Analysis
Gelan Miao, Rui Lu, Tanyong Pipanmekaporn, Srisuluk Kacha, Atirut Supphapipat, Natsuda Phothikun, Phut Jewprasertpan, Kaweesak Chittawatanarat
Diabetes/Metabolism Research and Reviews.2026;[Epub] CrossRef
Simultaneous assessment of stress hyperglycemia ratio and glucose variability to predict all-cause mortality in sepsis patients across different glucose metabolic states: an observational cohort study with interpretable machine learning approach
Fuxu Wang, Yu Guo, Chucheng Jiao, Shuangmei Zhao, Liutao Sui, Zhi Mao, Ruogu Lu, Rongyao Hou, Xiaoyan Zhu
International Journal of Surgery.2026; 112(1): 1219. CrossRef
Forecasting diabetes and sepsis mortality trends using advanced time-series models in United States from 1999 to 2030
Gabriele Volucke, Brandon Xian Ch’ng, Moaz Ahmad, Syed Muhammad Ali Hassnain, Toqeer Ahmed, Khadija Khizar Khan, Obaid Ur Rahman, Rowena Rachel George, Mustafa Elhaj, Syed Anjum Gardezi, Muhammad Azhar Waheed Khan, Abdulqadir J. Nashwan, Eeshal Zulfiqar,
Journal of Diabetes & Metabolic Disorders.2026;[Epub] CrossRef
Association between a Single-time Measurement of Fatty Liver Index and Occurrence of Sepsis among Individuals without Excessive Alcohol Consumption
Dayeong Kim, Sang Hoon Han, Eun Hwa Lee, Hye Seong, Kyu-na Lee, Yebin Park, Kyung-Do Han
Infection & Chemotherapy.2025; 57(3): 389. CrossRef
Impact of Diabetes on Clinical Characteristics and Prognosis in Sepsis: A Retrospective Study
Wen-Wen Han, Jian-Jiang Fang
Journal of Inflammation Research.2025; Volume 18: 13823. CrossRef

Metabolic Risk/Epidemiology
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; Diabetes Metab J. 2025;49(4):837-847. Published online February 14, 2025; DOI: https://doi.org/10.4093/dmj.2024.0536

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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.

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Multiparity as a key variable in metabolism and pregnancy research
Tracy K Her, V Pszczolkowski, Grace Chung, Laura A Woollett, Emilyn U Alejandro
Current Opinion in Physiology.2026; 47: 100926. CrossRef
Baseline and longitudinal changes of body roundness index and incident type 2 diabetes: evidence from the UK Biobank cohort
Xuanli Zhao, Fangyuan Jing, Yanan Ren, Jing Zhu, Xinzhe Jing, Meiqun Lv, Ke Huang, Jing Guo, Jiayu Li, Xiaohui Sun, Yingying Mao, Ding Ye
BMJ Open Diabetes Research & Care.2025; 13(5): e005339. CrossRef

Others
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; Diabetes Metab J. 2025;49(4):883-892. Published online February 13, 2025; DOI: https://doi.org/10.4093/dmj.2024.0537; Correction in: Diabetes Metab J 2026;50(2):432

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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.

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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.

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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
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Basic and Translational Research
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; Diabetes Metab J. 2025;49(3):421-435. Published online January 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0398

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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.

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Differential effects of prophylactic iron supplementation on physiological gestational anemia and post-IDA gestational anemia: a study based on a rat model
Zelin Zhang, Limin Lai, Ziping Liu, Sili Liu, Liping Qu, Wenjun Zou
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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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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.

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Reverse translational approach to clarify the strong potency of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor
Sun-Hwa Park, Hye-Young Ji, Ji-Soo Choi, Kyung Seok Oh, Jihoon Lee, Minyeong Pang, Im-Sook Song, Joon Seok Park
The Journal of Pharmacology and Experimental Therapeutics.2025; 392(8): 103650. CrossRef

Sulwon Lecture 2024

Basic and Translational Research
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

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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.

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Carlos Cruz‐Cortés, Silvia Micháliková, Petronela Rezbáriková, L. Michel Espinoza‐Fonseca, Jana Viskupičová
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Na Lin, Yaoyao Liang, Minying Tang, Fei Liu, Liuyan Chen, Lvying Wu, Yunfeng Fu, Zhuoyu Li, Lingfeng Zhu, Jin Chen, Yuelin Zhang
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Potential Involvement of PI3K/AKT Signaling Pathway in the Protective Effects of Rhinacanthus nasutus Against Diabetic Nephropathy-Induced Oxidative Stress
Junyu Liu, Yehao Lin, Xudong Yi, Min Zhang, Pharkphoom Panichayupakaranant, Joseph Buhagiar, Haixia Chen
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Original Article

Genetics
Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes: Siqian Gong, Hong Lian, Yating Li, Xiaoling Cai, Wei Liu, Yingying Luo, Meng Li, Si-min Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Qian Ren, Xiuying Zhang, Jing Chen, Jing Wu, Xianghai Zhou, Xirui Wang, Xueyao Han, Linong Ji; Diabetes Metab J. 2025;49(2):321-330. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0159

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Background
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

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Diabetes associated with HNF1B: beyond Occam’s razor—A case report
Carolina Sager-La Ganga, Clara Solà, Karen Castillo, Carme Figueredo, Ignacio Conget
Acta Diabetologica.2025; 62(8): 1347. CrossRef

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.

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Original Article

Pharmacotherapy
Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus: Mijin Kim, Seung Chan Kim, Jinmi Kim, Bo Hyun Kim; Diabetes Metab J. 2025;49(1):49-59. Published online October 24, 2024; DOI: https://doi.org/10.4093/dmj.2024.0105

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Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort.
Methods
This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years.
Results
After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group.
Conclusion
There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers.

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Reviews

Drug/Regimen
Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus: Ja Young Jeon, Dae Jung Kim; Diabetes Metab J. 2024;48(5):837-846. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0317

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People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.

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Cardiovascular Risk/Epidemiology
Artificial Light at Night and Type 2 Diabetes Mellitus: Jong-Ha Baek, Yong Zhu, Chandra L. Jackson, Yong-Moon Mark Park; Diabetes Metab J. 2024;48(5):847-863. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0237

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The widespread and pervasive use of artificial light at night (ALAN) in our modern 24-hour society has emerged as a substantial disruptor of natural circadian rhythms, potentially leading to a rise in unhealthy lifestyle-related behaviors (e.g., poor sleep; shift work). This phenomenon has been associated with an increased risk of type 2 diabetes mellitus (T2DM), which is a pressing global public health concern. However, to date, reviews summarizing associations between ALAN and T2DM have primarily focused on the limited characteristics of exposure (e.g., intensity) to ALAN. This literature review extends beyond prior reviews by consolidating recent studies from 2000 to 2024 regarding associations between both indoor and outdoor ALAN exposure and the incidence or prevalence of T2DM. We also described potential biological mechanisms through which ALAN modulates glucose metabolism. Furthermore, we outlined knowledge gaps and investigated how various ALAN characteristics beyond only light intensity (including light type, timing, duration, wavelength, and individual sensitivity) influence T2DM risk. Recognizing the detrimental impact of ALAN on sleep health and the behavioral correlates of physical activity and dietary patterns, we additionally summarized studies investigating the potential mediating role of each component in the relationship between ALAN and glucose metabolism. Lastly, we proposed implications of chronotherapies and chrononutrition for diabetes management in the context of ALAN exposure.

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Original Article

Metabolic Risk/Epidemiology
Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study: Ji-Hee Sung, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park; Diabetes Metab J. 2024;48(6):1105-1113. Published online August 19, 2024; DOI: https://doi.org/10.4093/dmj.2023.0444

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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.

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Effects of Celosia argentea L. leaf on Monosodium Glutamate (MSG)-Induced Uterine Leiomyoma In Wistar Rats: Experimental and Computational Perspectives
Akingbolabo Ogunlakin, Oluwafemi Ojo, Peluola Ayeni, Gideon Gyebi, Amel Elbasyouni, Oyindamola Awosola, Moyosoluwa Dada, Mamta Bisht, Edema Adeleye, Oluwadamilola Adedoyin, Opeyemi Akinmurele, Abdullahi Adegoke, Ajibola Adelakun, Omolola Oluwadara, Jumoke
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Review

Others
Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients: Jae-Seung Yun, Kyuho Kim, Yu-Bae Ahn, Kyungdo Han, Seung-Hyun Ko; Diabetes Metab J. 2024;48(4):531-545. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0310

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Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.

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Original Articles

Complications
Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim; Diabetes Metab J. 2024;48(6):1126-1134. Published online July 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0377

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Background
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
Methods
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
Results
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
Conclusion
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

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Tao Li, Kaili Chen, Yiting Sun, Linqi Zhang
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Hanfei Li, Yuxi Li, Bo Zhang, Wenhao Cheng, Guowei Ma, Jin Rong, Shiru Duan, Di Feng, Tingting Zhao
International Journal of Molecular Medicine.2026; 57(4): 1. CrossRef
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Omar Emiliano Aparicio-Trejo, Estefani Yaquelin Hernández-Cruz, Laura María Reyes-Fermín, Zeltzin Alejandra Ceja-Galicia, José Pedraza-Chaverri
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Chronic succinate exposure does not cause liver injury
Joseph Balnis, Emily L. Jackson, Lisa A. Drake, Catherine E. Vincent, Hwajeong Lee, Harold A. Singer, Ariel Jaitovich
American Journal of Physiology-Endocrinology and Metabolism.2025; 329(1): E39. CrossRef
Succinate Facilitates CD4+ T Cell Infiltration and CCL1 Production to Promote Myofibroblast Activation and Renal Fibrosis in UUO Mice
Yuandong Tao, Wei Zhang, Dehong Liu, Hualin Cao, Xiaoyu Yi, Xiangling Deng, Pin Li, Xiaoli Shen, Huixia Zhou
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Pathophysiology
Recent Glycemia Is a Major Determinant of β-Cell Function in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jiyoon Lee, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2024;48(6):1135-1146. Published online June 17, 2024; DOI: https://doi.org/10.4093/dmj.2023.0359

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Background
Progressive deterioration of β-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to β-cell function in T2DM.
Methods
In a T2DM cohort of 470 adults (disease duration 0 to 41 years), β-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of β-cell function (HOMA-B) derived from a 75 g oral glucose tolerance test (OGTT). The relative contributions of age, sex, disease duration, body mass index, glycosylated hemoglobin (HbA1c) levels (at the time of the OGTT), area under the curve of HbA1c over time (HbA1c AUC), coefficient of variation in HbA1c (HbA1c CV), and antidiabetic agents use were compared by standardized regression coefficients. Longitudinal analyses of these indices were also performed.
Results
IGI, DI, DI_O, and HOMA-B declined over time (P<0.001 for all). Notably, HbA1c was the most significant factor affecting IGI, DI, DIO, and HOMA-B in the multivariable regression analysis. Compared with HbA1c ≥9%, DI was 1.9-, 2.5-, 3.7-, and 5.5-fold higher in HbA1c of 8%–<9%, 7%–<8%, 6%–<7%, and <6%, respectively, after adjusting for confounding factors (P<0.001). Conversely, β-cell function was not affected by the type or duration of antidiabetic agents, HbA1c AUC, or HbA1c CV. The trajectories of the IGI, DI, DIO, and HOMA-B mirrored those of HbA1c.
Conclusion
β-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM.

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Zhuolin Zhou, Nan Gao, Jiaojiao Liu, Xuerong Ma, Zhijuan Ge, Cheng Ji
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Synergistic benefit of thiazolidinedione and sodium-glucose cotransporter 2 inhibitor for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a 24-week, open-label, randomized controlled trial
Minyoung Lee, Sukchul Hong, Yongin Cho, Hyungjin Rhee, Min Heui Yu, Jaehyun Bae, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
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Others
Serum Magnesium Levels Are Negatively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Mellitus: A Real-World Study: Man-Rong Xu, Ai-Ping Wang, Yu-Jie Wang, Jun-Xi Lu, Li Shen, Lian-Xi Li; Diabetes Metab J. 2024;48(6):1147-1159. Published online May 29, 2024; DOI: https://doi.org/10.4093/dmj.2023.0401

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Background
There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM.
Methods
This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893).
Results
After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P<0.001 for trend; abdominal obesity: 71.5%, 70.5%, 68.2%, 66.4%, and 64.5%, respectively, P=0.001 for trend). After controlling for confounders, there were clearly negative associations of serum magnesium levels and quintiles with obesity and abdominal obesity in T2DM. Moreover, C-reactive protein partly mediates the effect of serum magnesium on obesity and abdominal obesity (P=0.016 and P=0.004, respectively).
Conclusion
The significantly negative relationship between serum magnesium and the risk of obesity and abdominal obesity was observed in T2DM. Furthermore, the independently negative association of serum magnesium with obesity may be explained by its anti-inflammatory functions. Serum magnesium levels may be applied to assess the risk of obesity and abdominal obesity in T2DM.

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BMC Geriatrics.2025;[Epub] CrossRef
Physiological role of magnesium in the animal body: biochemical mechanisms and clinical significance
V. O. Danchuk, V. I. Karpovskyi, O. V. Danchuk, V. V. Danchuk, M. G. Chesak, B. V. Gutyj, P. V. Karpovskyi, V. V. Karpovskyi, V. B. Todoriuk
Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies.2025; 27(119): 185. CrossRef
Magnesium Matters: A Comprehensive Review of Its Vital Role in Health and Diseases
Ghizal Fatima, Andrej Dzupina, Hekmat B Alhmadi, Aminat Magomedova, Zainab Siddiqui, Ammar Mehdi, Najah Hadi
Cureus.2024;[Epub] CrossRef

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