Diabetes & Metabolism Journal

Original Article

Complications
Differential Associations of Social Determinants of Health with Diabetic Kidney Disease and Treatment Targets in Korean Adults with Diabetes: Yeoree Yang, Kyungdo Han, Young-Sang Lyu, Yun Kyung Cho, Kyeong Hye Park, Sang Mo Hong, Committee of Planning, Korean Diabetes Association; Received May 13, 2026 Accepted July 26, 2026 Published online September 30, 2026; DOI: https://doi.org/10.4093/dmj.2026.0534 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Social determinants of health (SDOH) are linked to adverse diabetes outcomes internationally, but it remains unclear whether these associations are uniform or concentrated across major treatment targets in Korea’s universal-coverage setting.
Methods
We analyzed two Korea National Health and Nutrition Examination Survey cohorts (2021–2024, n=3,129; 2011–2014, n=2,602). A 4-item SDOH composite was derived from 14 candidate items; because the cohort×SDOH interaction was nonsignificant (P=0.36), the cohorts were pooled (n=5,731). Outcomes included diabetic kidney disease (DKD)-related laboratory abnormalities, defined using Kidney Disease: Improving Global Outcomes (KDIGO)-consistent single-measurement thresholds, severe hyperglycemia (glycosylated hemoglobin [HbA1c] ≥8%), uncontrolled blood pressure (≥140/85 mm Hg), and elevated low-density lipoprotein cholesterol (LDL-C; ≥100 mg/dL). Associations were analyzed using survey-weighted logistic regression adjusted for age, sex, body mass index, and cohort.
Results
The composite showed a dose-response association with DKD-related laboratory abnormalities (15.9% [score 0] to 34.2% [score ≥3]; odds ratio [OR] per +1 item, 1.23; 95% confidence interval [CI], 1.14 to 1.33; P<0.001). It was associated with severe hyperglycemia (OR, 1.13; 95% CI, 1.03 to 1.23), but not uncontrolled blood pressure (OR, 0.95; 95% CI, 0.88 to 1.02) or elevated LDL-C (OR, 1.00; 95% CI, 0.94 to 1.08). The HbA1c association was threshold-dependent, emerging only at severe-hyperglycemia levels. This pattern persisted among actively treated patients. Sequential adjustment for HbA1c ≥8% and blood pressure attenuated the SDOH–DKD association by less than 1%.
Conclusion
Cumulative social disadvantage was associated with DKD-related laboratory abnormalities and severe hyperglycemia, but not failure to meet blood pressure or lipid targets. These exploratory findings may inform future SDOH assessment in Korean diabetes care. Longitudinal registry-linked studies are needed to confirm chronicity and temporality.

Reviews

Pharmacotherapy
Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies: Ji Yoon Kim, Nam Hoon Kim; Diabetes Metab J. 2026;50(5):844-862. Published online September 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0702

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Abstract PDF PubReader ePub: Incretin-based therapies have transformed the treatment of type 2 diabetes mellitus and obesity by producing a weight-loss magnitude that was previously achievable only through intensive caloric restriction or bariatric surgery. This therapeutic shift has moved the clinical focus from the quantity of weight loss to the quality of weight loss. Lean mass reduction is frequently observed during weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual glucose-dependent insulinotropic polypeptide/GLP-1RAs, or emerging multi-agonists. However, loss of lean body mass does not necessarily indicate equivalent loss of contractile skeletal muscle or sarcopenia. Incretin-based therapy is generally associated with preferential fat mass reduction, relative preservation of lean mass, and potential improvement in muscle quality through reduced myosteatosis. Thus, the clinically relevant question is whether incretin-associated body-composition changes lead to deterioration in muscle strength or physical performance, an increased risk of falls or fractures, or impaired quality of life. Available evidence does not show obvious functional harm; however, long-term data remain limited, especially in people with reduced muscle reserve. A muscle-conscious approach that integrates body-composition assessment, functional monitoring, resistance training, nutritional optimization, and emerging pharmacologic muscle-preserving strategies is needed to achieve high-quality weight loss.

Pathophysiology
Hypothalamic Inflammaging: A Central Driver of Type 2 Diabetes Mellitus and Metabolic Disease in Aging: Sang Hee Lyoo, Ki Hun Kim, Ki Woo Kim; Diabetes Metab J. 2026;50(5):863-883. Published online September 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0599

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Abstract PDF PubReader ePub: Aging is a major risk factor for type 2 diabetes mellitus (T2DM) and is accompanied by chronic, low-grade inflammation known as inflammaging. Emerging evidence indicates that the hypothalamus, a central regulator of energy and glucose homeostasis, undergoes age-associated inflammatory remodeling that contributes to metabolic dysfunction. In particular, glial cells, including microglia, astrocytes, tanycytes, and neural stem cells, acquire senescence-associated phenotypes characterized by impaired homeostatic functions and increased secretion of pro-inflammatory mediators. These changes disrupt hypothalamic neuronal circuits involved in glucose sensing, energy balance, and insulin responsiveness, thereby potentially promoting systemic insulin resistance and T2DM progression. In this review, we summarize current evidence on the cellular and molecular mechanisms of hypothalamic glial inflammaging and discuss how age-related glial dysfunction may contribute to metabolic abnormalities. We also highlight emerging therapeutic strategies targeting neuroinflammation and glial senescence for the prevention and treatment of age-associated T2DM.

Basic and Translational Research
Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics: Shibo Wei, Soyeon Shin, Dongryeol Ryu, Chang-Myung Oh; Diabetes Metab J. 2026;50(5):825-843. Published online September 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0310

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Abstract PDF Supplementary Material PubReader ePub: Sarcopenia in type 2 diabetes mellitus is increasingly recognized as a mechanistic consequence of chronic metabolic stress rather than mere age-related comorbidity. This review synthesizes evidence demonstrating how insulin resistance, hyperglycemia, lipotoxicity, and inflammation converge on skeletal muscle mitochondrial proteostasis to drive progressive decline. We evaluate seven pathway modules—mitochondrial dynamics, mitophagy, biogenesis, oxidative phosphorylation, nicotinamide adenine dinucleotide (NAD⁺)/sirtuin (SIRT)-linked regulation, protein import, and the mitochondrial unfolded protein response (UPRmt)—across an evidence map encompassing basic, clinical, and multi-omics studies. Dynamics and mitophagy represent mechanistically central quality-control nodes; their impairment permits dysfunctional organelle accumulation and promotes atrophic cascades. Direct evidence density, however, remains weighted toward oxidative phosphorylation and mitochondrial biogenesis. NAD⁺/SIRT-linked regulation, protein import fidelity, and UPRmt represent mechanistically upstream but comparatively underinvestigated signals. We propose a diabetes-centered framework where mitochondrial proteostasis failure mediates atrophy and reinforces insulin resistance via a self-amplifying feed-forward loop, supported by pathway responsiveness to coherent interventions. Human multi-omics data highlight network-level dysregulation rather than isolated defects, underscoring module-based biomarker strategies. Translationally, exercise remains the mechanistic cornerstone, while pathway-directed adjuncts—NAD⁺ precursor repletion, mitophagy modulators, and emerging pharmacotherapeutics—are warranted for patients with identifiable module-specific failure patterns.

Original Articles

Metabolic Risk/Epidemiology
Thigh Muscle Quality Predicts the Incidence of Type 2 Diabetes Mellitus: Hun Jee Choe, Steven B. Heymsfield, Michael D. Jensen, Soo Lim; Received December 7, 2025 Accepted March 31, 2026 Published online August 27, 2026; DOI: https://doi.org/10.4093/dmj.2025.1239 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Ectopic fat infiltration in skeletal muscle, particularly in the thigh, may impair muscle function and contribute to metabolic dysfunction. However, its predictive value for incident type 2 diabetes mellitus remains understudied.
Methods
We conducted a prospective cohort study of 2,129 East Asian adults (mean age, 57.4±16.9 years; body mass index, 25.0±3.9 kg/m²; 48.5% male) with one or more cardiometabolic risk factors but no diabetes at baseline. Low-density muscle (LDM) area was quantified using non-contrast computed tomography at the midthigh level, with attenuation values of 0–30 Hounsfield units defined as LDM. The association between LDM area and incident diabetes was assessed over a median follow-up of 7.4 years.
Results
During follow-up, 201 males (19.5%) and 156 females (14.1%) developed diabetes. Those who developed diabetes had higher baseline glycosylated hemoglobin levels (6.1%±0.3% vs. 5.7%±0.4%) and larger LDM areas (48.8±14.2 cm² vs. 38.1±13.2 cm², both P<0.05). In adjusted Cox models, a large LDM area was independently associated with incident diabetes (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.52–3.67 for males and HR, 2.15; 95% CI, 1.28–3.61 for females). Incorporating LDM area into models with traditional risk factors improved predictive accuracy (area under the curve increased from 0.810 to 0.838 in males and from 0.893 to 0.908 in females).
Conclusion
LDM area, an indicator of thigh muscle quality and intramuscular fat infiltration, is an independent predictor of incident diabetes.

Basic and Translational Research
FAM151A Regulates Insulin Secretion in Pancreatic β-Cells and Is Implicated in Pathogenesis of Type 2 Diabetes Mellitus: Jing Zhu, Chenchen Li, Shuaishuai Zhu, Jiawen Wu, Xinyu Zhu, Shixuan Zhuo, Yu Zhang, Zhuoxian Meng, Yan Chen; Received October 22, 2025 Accepted March 5, 2026 Published online August 6, 2026; DOI: https://doi.org/10.4093/dmj.2025.1061 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The pathophysiology of type 2 diabetes mellitus (T2DM) is characterized by insulin resistance in peripheral tissues and dysfunction of β-cells. However, the molecular mechanisms underlying β-cell dysfunction remain incompletely understood.
Methods
Analysis of single-cell RNA sequencing of T2DM islets was used to elucidate changes in family with sequence similarity 151 member A (Fam151a) expression. Deletion of Fam151a in INS-1E cells and mice was used to investigate the function of this gene in insulin secretion. Metabolic profiling and metabolomics analyses were used to decipher the effects of FAM151A on metabolic pathways.
Results
Using single-cell RNA sequencing, we identified that Fam151a was significantly downregulated in pancreatic β-cells under T2DM conditions. We next investigated the potential functions of FAM151A in β-cells in vitro and in vivo. FAM151A was localized in the endoplasmic reticulum, and its expression was reduced by high-glucose treatment in INS-1E cells. Genetic deletion of Fam151a in INS-1E cells resulted in proinsulin accumulation, insulin vesicle retention, and impaired insulin secretion. A mouse model with pancreatic β-cell-specific deletion of Fam151a displayed reductions in glucose- and potassium chloride (KCl)-stimulated insulin secretion, and impaired glucose tolerance, without alterations in insulin sensitivity or islet morphology. Integrated metabolic profiling and metabolomics analyses revealed that cellular Fam151a deficiency affects the adenosine triphosphate/adenosine diphosphate ratio, glycolysis, the pentose phosphate pathway, and the purine synthesis pathway.
Conclusion
Our study identifies FAM151A as a key regulator of insulin secretion in β-cells, providing a potential therapeutic target for the management of T2DM.

Pharmacotherapy
Efficacy and Safety of the Dual SGLT1 and SGLT2 Inhibitor JP-2266 in Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study: Eun Young Lee, Kyung Ah Han, Soo Heon Kwak, Jun Hwa Hong, You-Cheol Hwang, Gwanpyo Koh, Jing W. Hughes, Soomee Kim, Chang-Seok Lee, Bong-Soo Cha; Received November 13, 2025 Accepted April 20, 2026 Published online July 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.1152 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
To evaluate the efficacy and safety of JP-2266, a novel dual sodium-glucose co-transporter 1 (SGLT1)/SGLT2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.
Methods
In this 12-week, randomized, double-blind, placebo-controlled phase 2 trial, 156 patients with T2DM were randomly assigned (1:1:1) to receive once-daily JP-2266 5 mg (n=51), 10 mg (n=53), or placebo (n=52). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 12 (ClinicalTrials.gov identifier: NCT06144788).
Results
JP-2266 treatment led to significant, placebo-adjusted reductions in HbA1c of –0.94% (95% confidence interval [CI], –1.24 to –0.65; P<0.0001) for the 5 mg dose and –0.97% (95% CI, –1.26 to –0.68; P<0.0001) for the 10 mg dose. Significant reductions were also observed in fasting plasma glucose (–36.22 mg/dL [95% CI, –47.62 to –24.83] with 5 mg and –39.38 mg/dL [95% CI, –50.71 to –28.05] with 10 mg), and postprandial glucose (–62.30 mg/dL [95% CI, –84.97 to –39.64] with 5 mg and –66.89 mg/dL [95% CI, –89.71 to –44.07] with 10 mg) (all P<0.0001). JP-2266 also reduced body weight of –2.0 to –2.1 kg and systolic blood pressure (–3.6 mm Hg with 10 mg). Improvements in insulin resistance and β-cell function were also observed, as assessed by homeostasis model assessment. Adverse event rates were similar to placebo.
Conclusion
In patients with T2DM inadequately controlled by lifestyle alone, JP-2266 significantly improved glycemic control, reduced body weight and blood pressure, and was well tolerated over 12 weeks. These findings support further investigation of JP-2266 as a potential therapeutic option for T2DM.

Reviews

Pathophysiology
Revisiting Insulin Resistance in the Pathophysiology of Type 2 Diabetes Mellitus: A Multi-Organ Perspective: Soo Lim, Seung-Hwan Lee, Robert H. Eckel; Diabetes Metab J. 2026;50(4):641-665. Published online July 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0492

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Abstract PDF PubReader ePub

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a heterogeneous, multisystem disease that extends beyond chronic hyperglycemia to encompass cardiovascular disease, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease. Central to this expanded disease spectrum is insulin resistance arising from coordinated metabolic, inflammatory, neuroendocrine, and immune disturbances across multiple organs. Rather than a uniform defect in insulin signaling, insulin resistance represents a dynamic, tissue-specific, and stage-dependent process involving multiorgans, with substantial interorgan crosstalk. This review synthesizes contemporary mechanistic insights into the pathogenesis of insulin resistance in T2DM, integrating molecular pathways, organ-specific dysfunction, and systemic metabolic networks. Ectopic lipid accumulation, mitochondrial dysfunction, chronic low-grade inflammation, immune dysregulation, and gut dysbiosis are highlighted as convergent processes that impair insulin action and drive clinical heterogeneity. Insulin resistance is further contextualized within the cardiovascular–kidney–metabolic syndrome framework, which unifies metabolic, renal, and cardiovascular disease through shared upstream mechanisms. In addition, how contemporary glucose-lowering therapies exert benefits beyond glycemic control by targeting insulin resistance, metabolic reprogramming, and interorgan crosstalk is discussed. Collectively, insulin resistance is positioned as a central pathophysiological driver of T2DM and its complications, supporting a shift toward mechanism-based, organ-protective, and precision-oriented therapeutic strategies.

Citations

Citations to this article as recorded by

Mitochondrial Dynamics in Diabetes Mellitus and Its Complications: Mechanisms, Pathological Roles, and Therapeutic Implications
Guohua Wang, Yige Zhao, Gaiting Liu, Yuhang Du, Shuchang Liu, Yang Yang, Sitong Bu, Baosheng Zhao
International Journal of Molecular Sciences.2026; 27(19): 8451. CrossRef

Pharmacotherapy
Finerenone in Asian Patients with Type 2 Diabetes Mellitus and Albuminuric Chronic Kidney Disease: From Evidence to Implementation: Masayuki Yamanouchi, Kengo Furuichi, Takashi Wada; Diabetes Metab J. 2026;50(4):629-640. Published online July 1, 2026; DOI: https://doi.org/10.4093/dmj.2026.0306

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Abstract PDF PubReader ePub

Finerenone reduces kidney and cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and albuminuric chronic kidney disease (CKD). Recent Asian subgroup, pooled, combination-therapy, Asian versus non-Asian, and real-world analyses have expanded the evidence base relevant to Asian practice. These data support the consistency of finerenone efficacy and safety in Asian patients and do not support withholding treatment on the basis of Asian ethnicity alone. However, the central question in Asia is shifting from whether finerenone is effective to how eligible patients can be identified, treated, monitored, and continued on therapy in routine care. This review summarizes Asian evidence from the FIDELIO-DKD, FIGARO-DKD, FIDELITY, and CONFIDENCE programs and emerging Asian real-world data. Focus is placed on persistent albuminuric risk, potassium monitoring, treatment sequencing with sodium-glucose cotransporter 2 inhibitors, and implementation feasibility across heterogeneous health-care systems. Finerenone should be considered an evidence-based add-on therapy when baseline potassium and kidney function are appropriate and early laboratory monitoring can be delivered. Simultaneous or early combination therapy may be appropriate in selected high-risk patients, but is not a universal default strategy. The practical priority is to strengthen CKD phenotyping, albuminuria testing, structured potassium monitoring, and care pathways that support sustained use of trial-proven therapy.

Citations

Citations to this article as recorded by

Finerenone in Asian patients with diabetic kidney disease: evaluating the evidence for “better efficacy”
Siqian Gong, Linong Ji
Clinical Kidney Journal.2026;[Epub] CrossRef

Original Articles

Complications
Cardiorespiratory Fitness and Risk of Microvascular Complications in Patients with Type 2 Diabetes Mellitus: Anning Xu, Haofeng Zhou, Chaofan Wang, Qian He, Ping Wu, Wenjing Wu, Hongjiang Wu, Alice P.S. Kong, Huanyi Cao, Haixia Guan, Yunjiu Cheng; Received November 5, 2025 Accepted February 10, 2026 Published online May 18, 2026; DOI: https://doi.org/10.4093/dmj.2025.1109 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the association between cardiorespiratory fitness (CRF) and the risk of incident microvascular complications in patients with type 2 diabetes mellitus (T2DM), as well as the effects of genetic risk and potential mediation by circulating biomarkers.
Methods
This prospective analysis included 3,102 adults with T2DM from the UK Biobank. CRF was estimated as maximal oxygen uptake using a submaximal cycle test and categorized as low, moderate, or high. Cox proportional hazards models estimated hazard ratios (HRs) for incident diabetic nephropathy, retinopathy, and neuropathy. Interactions with a polygenic risk score and mediating roles of biomarkers were evaluated.
Results
Over a median follow-up of 12.47-years, 331 nephropathy, 268 retinopathy, and 88 neuropathy cases were recorded. Compared to low CRF, moderate and high CRF were associated with a 22% (HR, 0.78; 95% confidence interval [CI], 0.61 to 0.99) and 45% (HR, 0.55; 95% CI, 0.36 to 0.85) lower risk of nephropathy, respectively. Each 1-metabolic equivalent of task increment in CRF was linked to 11% lower nephropathy risk. No significant associations were found for retinopathy or neuropathy. Genetic predisposition did not modify the association between CRF and diabetic nephropathy. Triglycerides and white blood cell count accounted for 7.46% and 12.88% of the association, respectively.
Conclusion
Higher CRF is independently associated with a lower risk of diabetic nephropathy in T2DM, and genetic risk does not alter this relationship. The association is partially mediated by triglycerides and white blood cell count. Assessing CRF may improve risk stratification and prevention of diabetic kidney disease.

Cardiovascular Risk/Epidemiology
Oxidized Lipoproteins as Independent Predictors of Major Adverse Cardiovascular Events in Type 2 Diabetes Mellitus with Coronary Heart Disease: A Multicenter Prospective Cohort Study: Jun-Xu Gu, Juan Huang, Ai-Min Zhang, Yue Yin, Zi-Wei Wang, Hui-Zhang Bao, Shan-Shan Li, Na Zhang, Li Qin, Zhi-Hong Yue, Kun Wang, Mei Jia, Chun-Yan Wang, Lin Pei, Ming Su; Received October 15, 2025 Accepted February 6, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4093/dmj.2025.1029 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub

Background
Oxidized lipoproteins contribute to atherosclerosis and metabolic dysfunction; however, their prognostic significance for major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and coexisting coronary heart disease (CHD) remains unclear.
Methods
This multicenter cohort included 3,733 patients with angiographically confirmed T2DM-CHD, followed for 5 years. Baseline circulating oxidized high-density lipoprotein cholesterol (ox-HDL-C), oxidized low-density lipoprotein cholesterol (ox- LDL-C), and oxidized lipoprotein(a) (ox-Lp(a)) were measured, and associations with coronary severity, β-cell function, and MACEs were analyzed using Cox regression, Kaplan-Meier, and restricted cubic spline models.
Results
Patients with MACEs had higher baseline ox-HDL-C, ox-LDL-C, and ox-Lp(a), correlating with greater coronary lesion burden and impaired β-cell function. Restricted cubic spline analyses revealed nonlinear, dose-dependent associations, with MACEs risk increasing above thresholds of 19.88 ng/mL (ox-HDL-C), 25.71 ng/mL (ox-LDL-C), and 19.96 μmol/L (ox-Lp(a)), with sexspecific differences observed. In Cox proportional hazards models, individuals in the highest quartile of oxidized lipoproteins had significantly elevated 5-year MACEs risk compared to those in the lowest quartile, and these associations remained robust after adjusting for confounders (ox-HDL-C: adjust hazard ratio [HR], 1.872; 95% confidence interval [CI], 1.408 to 2.489; P<0.001; ox- LDL-C: adjust HR, 2.239; 95% CI, 1.686 to 2.974; P<0.001; ox-Lp(a): adjust HR, 1.917; 95% CI, 1.442 to 2.549; P<0.001).
Conclusion
Oxidized lipoproteins are independent predictors of MACEs in patients with T2DM-CHD and reflect vascular and metabolic dysfunction. Incorporating oxidized lipoprotein profiling into clinical risk assessment may improve early identification of high-risk individuals and guide preventive strategies.

Citations

Citations to this article as recorded by

Global research trends and hotspots evolution in type 2 diabetes mellitus complicated with coronary heart disease: a bibliometric analysis from 2016 to 2026
Chunying He, Xiaohua Hu, Xiaolan Yin, Min Zhan, WeiYi Cao, Rui Li
Frontiers in Endocrinology.2026;[Epub] CrossRef
Reconceptualizing Dyslipidemia: Diversity of Lipid Imbalances and Their Clinical Implications; A Narrative Review
Ali Mansoursamaei, Amirhossein Yadegar, Fatemeh Mohammadi, Seyed Arsalan Seyedi, Soghra Rabizadeh, Sahar Karimpour Reyhan, Alireza Esteghamati, Manouchehr Nakhjavani
Health Science Reports.2026;[Epub] CrossRef
Oxidative Stress in Vascular Aging: Therapeutic Potential of the Antioxidant Paradox. A State-of-the-Art Review
Aleyma Veliz Perez, Mihaela Badea, Sehrish Bilal
Antioxidants.2026; 15(9): 1152. CrossRef

Review

Others
Neutrophil-Linked Inflammatory Mechanisms and Biomarkers in Diabetic Microvascular Complications: Junseo Kim, Daeun Jung, Da Hyun Kang, Hyeongseok Kim, Junyoung O. Park, Jun Young Heo, Seong Eun Lee, Hyun Jin Kim, Ju Hee Lee, Yea Eun Kang, Bon Jeong Ku; Diabetes Metab J. 2026;50(3):450-471. Published online April 27, 2026; DOI: https://doi.org/10.4093/dmj.2025.1034

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Abstract PDF PubReader ePub: Diabetic microvascular complications, including nephropathy, retinopathy, and neuropathy, are major causes of morbidity in diabetes. Increasing evidence highlights neutrophils as key contributors to the chronic inflammatory processes underlying these complications. In the diabetic environment, neutrophils exhibit impaired recruitment, defective phagocytosis, dysregulated degranulation, and excessive production of reactive oxygen species and neutrophil extracellular traps (NETs). These dysfunctions not only reduce pathogen clearance but also exacerbate tissue injury through persistent low-grade inflammation. Furthermore, neutrophils interact with other immune cells, such as macrophages, dendritic cells, T cells, and B cells, perpetuating immune imbalance and tissue damage. Various neutrophil-derived cytokines and granular proteins also influence vascular permeability and endothelial dysfunction. In recent years, neutrophil-related biomarkers—such as absolute neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-neutrophil ratio, and systemic immune-inflammation index—have gained attention as accessible and cost-effective tools for predicting and monitoring diabetic microvascular complications. This review summarizes the multifaceted roles of neutrophils in the pathogenesis of diabetic microvascular disease and highlights emerging clinical applications of neutrophil-based inflammatory biomarkers. A better understanding of neutrophil-driven mechanisms may open new avenues for early diagnosis, therapeutic intervention, and personalized care in diabetic patients.

Original Articles

Basic and Translational Research
Spatial Transcriptomic Analysis of Human Visceral Adipose Tissue in Different Metabolic Status: Methodological Validation and Application: Jisu Jung, Qingzhi Huang, Sumin Lee, Dohoon Kim, Hyunmyeong Oh, Young Suk Park, Hyung Joon Kim, Jung-Kwon Kim, Tae Jung Oh, Amos C. Lee, Joon Ho Moon, Sung Hee Choi; Received October 15, 2025 Accepted January 23, 2026 Published online April 22, 2026; DOI: https://doi.org/10.4093/dmj.2025.1028 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Adipose tissue consists predominantly of lipid-filled adipocytes with limited cytoplasmic space, posing challenges for spatial transcriptomic analysis. Spatially-resolved laser-activated cell sorting (SLACS) enables precise isolation of tissue sections, offering a strategy to overcome these challenges.
Methods
Human visceral adipose tissue (VAT) samples from lean individuals and those with obesity and type 2 diabetes mellitus (Ob-DM) were analyzed. SLACS was used to isolate perivascular (PV) and adipocyte-rich (AD) areas, followed by full-length RNA sequencing to investigate pathways, cellular composition, and post-transcriptional regulation.
Results
PV and AD areas exhibited distinct transcriptional patterns. Fibro-inflammatory signatures and vascular remodeling pathways were enriched in the PV, while lipid metabolism and antioxidant pathways were predominant in the AD. Cellular deconvolution suggested area- and disease-specific cell composition. Post-transcriptional modifications, including adenosine-to-inosine (A-to-I) RNA editing and isoform switching in metabolic genes were observed in Ob-DM, suggesting a potential contributor to adipose dysfunction.
Conclusion
This study demonstrates the technical feasibility of SLACS-based spatial transcriptomic profiling in human VAT, with exploratory biological findings that warrant validation in larger cohorts.

Technology/Device
Association between Continuous Glucose Monitoring and Risk of Acute Diabetes-Related Complications in Pediatric Type 1 Diabetes Mellitus: A Nationwide Cohort Study: Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim; Received August 21, 2025 Accepted February 3, 2026 Published online April 22, 2026; DOI: https://doi.org/10.4093/dmj.2025.0794 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Evidence supporting the benefits of continuous glucose monitoring (CGM) in reducing diabetes-related complications remains scarce. This study aimed to investigate the association between CGM and diabetes-related complications, specifically diabetic ketoacidosis (DKA) and severe hypoglycemia in children and adolescents with type 1 diabetes mellitus (T1DM).
Methods
From the Korean Nationwide Cohort (2016–2022), we included children and adolescents (aged <19 years) with T1DM who received rapid-acting insulin between 2019 and 2022. The primary outcomes were DKA and severe hypoglycemia. Adjusted hazard ratios (HRs) for the primary outcomes were compared between CGM users and non-users using Cox proportional hazards regression models. Additionally, among the CGM users, the frequencies of DKA and severe hypoglycemia were compared before and after CGM initiation using a paired t-test.
Results
This study included 3,765 children and adolescents (2,313 CGM users and 1,452 non-users). During a median follow-up of 2.7 years, CGM users showed a lower risk of DKA (adjusted HR, 0.44; 95% confidence interval [CI], 0.35 to 0.56) and severe hypoglycemia (adjusted HR, 0.48; 95% CI, 0.29 to 0.79) than non-users. Among CGM users, the mean frequency of DKA decreased by 64%, and that of severe hypoglycemia decreased by 57% after CGM initiation (P<0.001 for both).
Conclusion
In this nationwide cohort study, CGM was associated with a reduced risk of DKA and severe hypoglycemia in children and adolescents with T1DM.

Genetics
Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus: Soobin Cho, Hyunsuk Lee, Joon Ha, Yeonsoo Park, Joon Ho Moon, Hak Chul Jang, Kyong Soo Park, Nam H. Cho, Michael Bergman, Soo Heon Kwak; Diabetes Metab J. 2026;50(5):1002-1013. Published online April 22, 2026; DOI: https://doi.org/10.4093/dmj.2025.0362

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Abstract PDF Supplementary Material PubReader ePub: Background
High 1-hour plasma glucose (1-h PG) level has been proposed by the International Diabetes Federation to identify high-risk individuals and diagnose type 2 diabetes mellitus (T2DM). In a longitudinal cohort, we examined T2DM risk, β-cell function, and the effects of genetic and lifestyle factors on high 1-h PG.
Methods
We analyzed 7,464 participants without T2D at baseline from a community-based prospective cohort in Korea, who underwent biennial 2-h 75-g oral glucose tolerance tests over 14 years. Incident T2D risk were assessed across 1-h PG groups: < 155, 155–208, and ≥ 209 mg/dL. In 6,588 participants with at least two 1-h PG measurements, we analyzed 1-h PG trajectories by T2D polygenic risk score (PRS; low, 1st quintile; intermediate, 2nd–4th quintiles; high, 5th quintile) and lifestyle, assessed using Life's Essential 8.
Results
Compared to the <155 mg/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; P<0.001) for 155–208 mg/dL, and 6.81 (95% CI, 5.81 to 7.98; P<0.001) for ≥209 mg/dL. Both groups had lower baseline disposition index compared to the <155 mg/dL group (57.3% and 72.7%, respectively; both P<0.001). Higher T2DM PRS was associated with elevated baseline 1-h PG (low: 131 mg/dL, intermediate: 141 mg/dL, high: 151 mg/dL) and faster increase in 1-h PG (1.36 vs. 1.85 vs. 2.21 mg/dL/year; all P<0.001). Importantly, healthy lifestyle attenuated the rate of increase across all PRS groups.
Conclusion
High 1-h PG predicts T2DM risk and is associated with β-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.

Complications
Objectively-Defined Sleep Regularity Is Associated with Macrovascular and Microvascular Complications among Individuals with Type 2 Diabetes Mellitus: A Cohort Study: Ying Zheng, Manrui Zhang, Hanzhang Wu, Jiahe Wei, Hui-Xin Wang, Torbjörn Åkerstedt, Xiaoyu Li, Xiao Tan; Received June 17, 2025 Accepted December 1, 2025 Published online April 17, 2026; DOI: https://doi.org/10.4093/dmj.2025.0530 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
To assess the association of accelerometer-measured sleep regularity with macrovascular and microvascular complications among individuals with type 2 diabetes mellitus (T2DM).
Methods
A total of 3,862 participants with T2DM at baseline participated. The sleep regularity metrics measured by wrist-worn accelerometers include sleep regularity index (SRI) and standard deviation (SD) of sleep duration. Incident macrovascular complications including coronary heart disease (CHD) and stroke, microvascular complications including diabetic neuropathy, diabetic kidney disease, and diabetic retinopathy were recorded. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for macrovascular and microvascular complications.
Results
During a median follow-up of 7.2 years, 410 composite macrovascular and 615 composite microvascular events occurred. Compared to regular sleepers (the highest tertile of SRI), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.29; 95% CI, 1.01 to 1.66) and stroke (HR, 1.97; 95% CI, 1.08 to 3.58). Compared to regular sleepers (the lowest tertile of sleep duration SD), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.44; 95% CI, 1.12 to 1.84), CHD (HR, 1.40; 95% CI, 1.07 to 1.82), and stroke (HR, 2.07; 95% CI, 1.13 to 3.81). For microvascular complications, no significant association of sleep regularity metrics was found (all P>0.05). However, the dose-response analysis suggested a potential nonlinear association between SRI and diabetic neuropathy, with lower SRI consistently associated with higher risk of diabetic neuropathy (HR, 1.92; 95% CI, 1.28 to 2.88; 5th percentile vs. 50th percentile).
Conclusion
An irregular sleep pattern across days is clinically relevant for increasing the risk of macrovascular complications and diabetic neuropathy among individuals with T2DM.

Lifestyle and Behavioral Interventions
Influence of Fibroblast Growth Factor 21 on Delayed Glycemic Improvement Following Acute Exercise in Type 2 Diabetes Mellitus: Ying Zhang, Dan Liu, Yurun Lu, Piao Kang, Xinyu Liu, Qinyi Wang, Anran Chen, Di Cheng, Liang Wu, Qi Li, Xiaolin Wang, Yanli Li, Yaorui Ye, Jingyi Yang, Jiacheng Ni, Qichen Fang, Zhe Huang, Aimin Xu, Weiping Jia, Yong Wang, Guowang Xu, Huating Li; Diabetes Metab J. 2026;50(4):770-784. Published online March 25, 2026; DOI: https://doi.org/10.4093/dmj.2024.0814

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Background
Exercise positively influences glycemic control. Some individuals experience greater glycemic stability on the day after exercise, even without additional physical activity. However, the mechanisms underlying this delayed glycemic improvement remain unclear.
Methods
Seventy-one patients with type 2 diabetes mellitus were assigned to either a 60-minute exercise group or a resting group. Serum fibroblast growth factor 21 (FGF21) levels and untargeted metabolomic profiles were assessed at multiple time points before and after exercise. Interstitial glucose levels were monitored using continuous glucose monitoring system. FGF21 knockout mice and wild-type littermates fed a high-fat diet underwent a 3-week exercise intervention and received FGF21 supplementation.
Results
Individuals exhibiting delayed glycemic improvement (responders) displayed a significantly stronger FGF21 response than non-responders. Baseline metabolites, including p-cresol sulfate and dimethylglycine, differed between responders and non-responders and were associated with the FGF21 response. Longitudinal time-series analyses revealed post-exercise differences in acylcarnitines, fatty acids, and complex lipids between responders and non-responders. Dynamic correlation and mediation analyses supported the role of FGF21 in modulating delayed glycemic improvement through regulation of lipid metabolism. In vivo FGF21 knockout and rescue experiments demonstrated that FGF21 is necessary for these metabolic shifts and the associated improvements in glucose tolerance and insulin sensitivity.
Conclusion
This study suggests that the baseline metabolome is associated with the magnitude of the post-exercise FGF21 response, which influences delayed glycemic improvement through regulation of lipid metabolism pathways.

Citations

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Fibroblast Growth Factor 21: Bridging Nutrient Stress Signaling and Exercise-Induced Adaptive Responses
Dae Ho Lee
Diabetes & Metabolism Journal.2026; 50(4): 669. CrossRef

Lifestyle and Behavioral Interventions
Lifestyle Combination Patterns as Key Modifiable Factors for Type 2 Diabetes Mellitus Risk among Middle-Aged Korean Men: Inji Lee, Hyunjung Lim; Diabetes Metab J. 2026;50(5):990-1001. Published online March 24, 2026; DOI: https://doi.org/10.4093/dmj.2025.0166

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Abstract PDF PubReader ePub: Background
The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide highlights the need to understand risk factors and effective prevention strategies. Although individual lifestyle factors associated with diabetes risk have been identified, research on their collective interactions is limited. This study aimed to identify lifestyle combination patterns in middle-aged Korean men and evaluate their impact on T2DM risk.
Methods
A total of 2,332 middle-aged men without T2DM at baseline (2001–2002) from the Korean Genome and Epidemiology Study (KoGES) cohort were included. T2DM incidence was tracked through the 8th follow-up survey (2017–2018). Lifestyle combination patterns were identified using factor analysis based on sociodemographic, lifestyle, and dietary data. Cox regression was used to assess T2DM incidence across patterns.
Results
Four lifestyle combination patterns were identified: ‘Healthy Lifestyle,’ ‘Low Carb & High Protein,’ ‘High SES & Irregular Lifestyle,’ and ‘Bad Eating Habits.’ The risk of developing T2DM varied across patterns. The ‘Healthy Lifestyle’ and ‘Low Carb & High Protein’ patterns showed a slight decrease in risk in T3, but the differences were not significant. The ‘High SES & Irregular Lifestyle’ pattern was associated with a higher T2DM risk in T3 than in T1 (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.05 to 1.55), but the association was attenuated after adjustment for family history. The ‘Bad Eating Habits’ pattern showed a 1.21-fold higher risk in T3 (HR, 1.21; 95% CI, 1.01 to 1.47).
Conclusion
This study underscores the existence of distinct lifestyle combination patterns and their differential implications for T2DM risk. These findings support the need for tailored preventive strategies based on lifestyle patterns.

Cardiovascular Risk/Epidemiology
Impact of Blood Pressure on Sudden Cardiac Arrest in Diabetic Patients: Yun Gi Kim, Hyoung Seok Lee, Chang-Ok Seo, Yeji Kim, Joo Hee Jeong, Kyung-Do Han, Jaemin Shim, Young-Hoon Kim, Jong-Il Choi; Diabetes Metab J. 2026;50(5):965-976. Published online March 6, 2026; DOI: https://doi.org/10.4093/dmj.2025.0339

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Abstract PDF Supplementary Material PubReader ePub: Background
Hypertension and diabetes mellitus (DM), including pre-hypertension and impaired fasting glucose (IFG), are associated with increased risk of sudden cardiac arrest (SCA). However, interaction between hypertension and DM needs further examination.
Methods
This study utilized data from the South Korean national healthcare insurance system. People who underwent nationwide health screening in 2012 were enrolled. The impact of blood pressure on SCA was evaluated in both diabetic and non-diabetic patients.
Results
A total of 4,593,706 people were analyzed with 3,097,423, 1,034,563, and 461,720 people included in non-DM, IFG, and DM group, respectively. Both high blood pressure (systolic, diastolic, and pulse) and DM were associated with an increased risk of SCA with the highest absolute risk observed in patients with both conditions. A significant interaction was found between blood pressure and DM (P for interaction <0.01): the relative influence of blood pressure on SCA risk was greater in the non-diabetic population. Importantly, in diabetic patients, a J-shaped association was observed; not only high but also low systolic blood pressure (<100 mm Hg) was associated with a significantly increased risk of SCA.
Conclusion
Although the risk of SCA was highest in people with both hypertension and DM, the degree of association between blood pressure and SCA was more pronounced in non-diabetic people. In patients with diabetes, both high and low systolic blood pressure are associated with an elevated risk of SCA. While controlling hypertension is crucial for all individuals, avoiding hypotension may be another important strategy for preventing SCA in people with diabetes or individuals with diabetes.

Type 1 Diabetes
Familial Occurrence of Type 1 Diabetes Mellitus in Korean Children and Adolescents: A Multicenter Study: Hae Sang Lee, Hwa Young Kim, Mi Yang, Yun Jeong Kim, Hyun Wook Chae, Kyungchul Song, Aram Yang, Hyo-Kyoung Nam, Young-Jun Rhie, Eungu Kang, Mo Kyung Jung, Yoonha Lee, Sung Yoon Cho, Insung Kim, Minji Im, Moon Bae Ahn, Su Jin Park, Soo Yeun Sim, Yoo-Mi Kim, Young-Lim Shin, Yong Hee Hong, Junghwan Suh, Sujin Kim, Seo Jung Kim, Min Hyung Cho, Yong Hyuk Kim, Jieun Lee, Su Jin Kim, Jisun Park, Eun Young Joo, Myung Ji Yoo, Minsun Kim, Han Sol Kim, Han Hyuk Lim, Jung Eun Moon, Kyungmi Jang, Chan Jong Kim, Jaehyun Kim; Received November 13, 2025 Accepted January 23, 2026 Published online March 5, 2026; DOI: https://doi.org/10.4093/dmj.2025.1149 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Data on the familial occurrence of type 1 diabetes mellitus (T1DM) in Korean pediatric populations are limited. This study evaluated the clinical characteristics of children with T1DM according to family history and estimated the T1DM prevalence among relatives.
Methods
We conducted a multicenter retrospective cohort study including patients aged ≤18 years newly diagnosed with T1DM at 18 university-affiliated hospitals in Korea between 2010 and 2024. The index child was defined as the first sibling diagnosed with T1DM and categorized according to the presence of affected parents or siblings. Familial T1DM prevalence was calculated for siblings, first-degree relatives, and twin pairs.
Results
Among 936 index children, 32 (3.4%) exhibited a T1DM family history. Compared with index children, subsequent-affected children presented with lower plasma glucose (300.0 mg/dL vs. 412.0 mg/dL, P=0.009) and glycosylated hemoglobin levels (10.4% vs. 12.6%, P<0.001), and a lower frequency of diabetic ketoacidosis (13.8% vs. 49.7%, P<0.001). Venous pH and serum bicarbonate levels were higher (7.4 vs. 7.3, P=0.005; 22.0 mmol/L vs. 17.0 mmol/L, P=0.004, respectively), whereas urine ketone levels were significantly lower (P<0.001). Sibling, first-degree relative, and twin-pair prevalence rates were 3.0% (23/779), 1.3% (34/2,651), and 42.9% (3/7), respectively.
Conclusion
In this multicenter Korean cohort, familial T1DM accounted for 3.4% of pediatric cases, which was lower than in Western populations. Subsequent-affected children exhibited milder metabolic decompensation at diagnosis than did index children, likely reflecting earlier recognition through family awareness and screening. These findings underscore the importance of early education and monitoring of at-risk relatives within affected families.

Reviews

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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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.

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Beyond Glycemic Control: Real-World 12-Month Effects of Insulin Glargine/Lixisenatide on Weight, Endogenous Insulin Secretion, and Albuminuria
Sadettin Ozturk, Elif Melis Baloğlu Akyol
Journal of Clinical Medicine.2026; 15(13): 5049. CrossRef
Short-Term Intensive Insulin Therapy as a Remission Induction Strategy in Newly Diagnosed Type 2 Diabetes Mellitus: A Systematic Review
Tahira Nasreen, Noor ul huda Awan, Mohammad Uzair, Sunita Kumawat, FNU Vanshika, Esha Sharma, Daniel E Cook, Ghazanfar Ali, Ahmad Sattar
Cureus.2026;[Epub] CrossRef
Prediction of Six-Month Glycemic Status in Type 2 Diabetes: Development and Internal Validation of a Multivariable Model
Andreea Diana Igna, Bianca-Lăcrimioara Petca, Paula-Alexandra Popovici, Ioana Moga, Titus David Moga, Timea Claudia Ghitea, Corina Cinezan, Mihaela Simona Popoviciu
Diagnostics.2026; 16(19): 3201. CrossRef

Basic and Translational Research
Heterogeneity and Clinical Relevance of Human Adipose Stromal and Progenitor Cells: Maxi Albert, Khansa Nalir, Jiawei Zhong, Lucas Massier; Diabetes Metab J. 2026;50(2):217-234. Published online March 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.1182

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Adipose stromal and progenitor cells (ASPCs) represent the largest cell population in human white adipose tissue (WAT). Despite their abundance, ASPC heterogeneity remains less well characterized compared to adipocytes or immune cells. Recent single-cell transcriptome studies provide unprecedented resolution of ASPC diversity and function. This review summarizes state-of-the-art approaches, including high-resolution single-cell methods, classical lineage and functional assays, to define ASPC populations. By systematically comparing recent datasets, we identify evidence for at least eight distinct ASPC-subtypes, which demonstrate specific marker genes and putative functional diversity. Along the adipogenic trajectory, these include uncommitted multipotent progenitors, intermediate and committed preadipocytes, and premature adipocytes. Additional populations comprise specialized anti-adipogenic, profibrotic, inflammatory, and fibroblast-like ASPCs. Other cell types are not consistently detected across studies, reflecting both biological and methodological variability, and the need for further validation studies. Better understanding of ASPC heterogeneity may improve the clinical assessment of metabolic disorders and support their treatment. We further discuss subtype-specific (dys)functions linked to fibrosis, inflammation and impaired adipogenesis and describe their increased abundance in metabolic disease. Together, this review integrates current knowledge on ASPC heterogeneity and highlights its clinical relevance, aiming to provide a unified framework for future studies on WAT remodeling and metabolic dysfunction.

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Cellular remodeling of lipedema affected subcutaneous adipose tissue
Sabrina Gohlke, Francisco Garcia-Carrizo, Robin Upmeyer, Tim J. Schulz
Frontiers in Cell and Developmental Biology.2026;[Epub] CrossRef

Original Articles

Guideline/Statement/Fact Sheet
Diabetes Fact Sheet 2025: Special Edition on Diabetes with Obesity and in Pregnancy: Se Eun Park, Se Hee Min, Jin Hwa Kim, Seung-Hwan Lee, Han Na Jung, Joon Ho Moon, Kyungdo Han, Seung-Hyun Ko, Bong Soo Cha, Sung Hee Choi; Diabetes Metab J. 2026;50(2):255-266. Published online March 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.1162

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Background
We evaluated epidemiologic trends and clinical characteristics in Koreans with diabetes and obesity and in those with diabetes in pregnancy.
Methods
We analyzed Korea National Health and Nutrition Examination Survey data (2012–2023) to assess obesity trends in people with diabetes and used the Korean National Health Insurance Service database (2013–2023) to evaluate diabetes in pregnancy.
Results
Among Korean adults with diabetes (≥19 years), 52.4% had obesity and 61.1% had abdominal obesity. Only 39.9% achieved the glycemic target (glycosylated hemoglobin <6.5%). The obesity prevalence was higher in younger age groups, and abdominal obesity showed an upward trend over the last 12 years. Diabetes in pregnancy increased despite declining total births, with gestational diabetes mellitus (GDM) rising from 7.6% to 12.4%, and pregestational diabetes from 0.9% to 2.1%, reflecting older maternal age and pre-pregnancy obesity. Women with prior GDM had a higher risk of postpartum type 2 diabetes mellitus (hazard ratio, 6.07; 95% confidence interval, 5.97 to 6.17).
Conclusion
Obesity and abdominal obesity are highly prevalent among Korean adults with diabetes, with abdominal obesity increasing over the past decade, and obesity disproportionately affects younger adults. Diabetes in pregnancy has also increased with older maternal age and worsening pre-pregnancy metabolic health, underscoring the need for early weight-focused prevention.

Citations

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Diabetes Fact Sheet 2025: Comparative Epidemiology and Clinical Features of Obese and Non-Obese Diabetes in Korea
Jin Hwa Kim, Bongseong Kim, Se Eun Park, Seung-Hyun Ko, Sung Hee Choi, Bong Soo Cha, Kyungdo Han, Seung-Hwan Lee
Diabetes & Metabolism Journal.2026; 50(2): 267. CrossRef
Diabetes in Pregnancy in Korea: Prevalence, Clinical Characteristics, and Postpartum Comorbidities
Joon Ho Moon, Han Na Jung, Bongseong Kim, Seung-Hyun Ko, Soo Heon Kwak, Kyung-Do Han, Sung Hee Choi
Diabetes & Metabolism Journal.2026; 50(2): 280. CrossRef
Targeted 3.34-Million CpG Site Sequencing Reveals Preliminary Cord Blood Epigenetic Alterations of Autism Spectrum Disorder: A Pilot Study Highlighting the PCDHA1–PCDHA8 Cluster
Marina Armas-González, Nieves Luisa González-González, Enrique González-Dávila, Olivia Orribo-Morales, José Ramón Castro-Conde, Candelaria González-Campos, Carlos Flores, José Miguel Lorenzo-Salazar, Rafaela González-Montelongo, Adrián Muñoz-Barrera, Erik
International Journal of Molecular Sciences.2026; 27(18): 8038. CrossRef

Guideline/Statement/Fact Sheet
Diabetes Fact Sheet 2025: Comparative Epidemiology and Clinical Features of Obese and Non-Obese Diabetes in Korea: Jin Hwa Kim, Bongseong Kim, Se Eun Park, Seung-Hyun Ko, Sung Hee Choi, Bong Soo Cha, Kyungdo Han, Seung-Hwan Lee, on Behalf of the Committee of Public Relation and Obese Diabetes Task Force Team of the Korean Diabetes Association; Diabetes Metab J. 2026;50(2):267-279. Published online March 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.1160; Correction in: https://doi.org/

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Background
The growing burden of obesity has profoundly influenced the epidemiology and phenotype of diabetes. This study aimed to compare the epidemiology and clinical features between obese and non-obese diabetes in Korean adults using nationwide database.
Methods
We analyzed data from the Korea National Health and Nutrition Examination Survey (2012–2023) to evaluate the prevalence and management of diabetes, as well as associated comorbidities. Data from the Korean National Health Insurance Service were used to assess antidiabetic medication use, metabolic surgery trends, and cancer outcomes.
Results
Diabetes prevalence was nearly twice as high in adults with obesity compared with those without (17.6% vs. 9.5%), with the larger difference observed in individuals aged 30 to 59 years. Obese diabetes was associated with higher rates of hypertension and dyslipidemia and lower rates of achieving glycemic, blood pressure, and lipid targets; only 21.0% achieved all three goals. Although sodium-glucose cotransporter 2 inhibitors and thiazolidinediones were more frequently prescribed in obese diabetes, overall use remained low. Metabolic surgery was less common in individuals with diabetes than in those without; sleeve gastrectomy predominated, while Roux-en-Y gastric bypass was performed more often in those with diabetes. Higher body mass index was associated with increased incidence of thyroid, breast, prostate, and kidney cancers.
Conclusion
Obese diabetes represents a distinct, high-risk phenotype in Korea, characterized by a greater cardiometabolic burden and suboptimal risk-factor control. Comprehensive management strategies integrating weight reduction with metabolic and cardiovascular risk control are essential to improve outcomes in this population.

Citations

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Discriminating prevalent type 2 diabetes among community-dwelling older adults with metabolic dysfunction-associated steatotic liver disease: a comparative analysis of 12 insulin resistance surrogates
Xianshang Zhu, Zengrui Wang, Yan Fang, Zong Ning, Xia Yang
Frontiers in Endocrinology.2026;[Epub] CrossRef
Coptidis Rhizoma for Obesity, Diabetes, and Dyslipidemia: An Integrated Meta-Analysis and In Silico Study
Chae-Yeon Kang, Yeon-Joo Yoo, Ji-Han Kim, Seung-Hoon Yoo, Hyun-Joo Kim, Min-Seong Lee, Byung-Cheol Lee
International Journal of Molecular Sciences.2026; 27(18): 8109. CrossRef

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; Diabetes Metab J. 2026;50(4):785-796. Published online February 23, 2026; DOI: https://doi.org/10.4093/dmj.2025.0766

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This study aimed 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 used 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 with individuals with 0 MET-min/wk of physical activity before 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 toward increased depression risk was observed among 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 it. 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; Diabetes Metab J. 2026;50(5):977-989. Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0569

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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.

Citations

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Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis
Jie Yang, Xuan Zhang, Lihong Luo, Zhenjiang Zheng, Chunlu Tan, Xubao Liu, Yonghua Chen
The Journal of Clinical Endocrinology & Metabolism.2026; 111(10): 2994. CrossRef
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Zhen-Hua Li, Cheng-Yang Hu, Xia-Juan Lu, Meng-Na Zhu, Shao-Lei Pu, Rui He, Kai Huang, Mao-Lin Chen, Guo-Peng Gao, Fang-Biao Tao, Xiu-Jun Zhang
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Complications
Optimizing Early Detection of Diabetic Kidney Disease through Synergistic Biomarkers and Serum Metabolites in Humans: 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; Diabetes Metab J. 2026;50(4):752-769. Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0193

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Background
Diabetic kidney disease (DKD) often progresses to end-stage renal disease more rapidly than nondiabetic kidney disease because of persistent hyperglycemia and early activation of multiple pathogenic pathways. Early detection of DKD is crucial for identifying subtle kidney damage before clinical symptoms appear.
Methods
This study combined human serum proteomics with 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 patients with type 2 diabetes mellitus (T2DM), 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 early DKD 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 the serum of patients with DKD. In db/db mice, all three biomarkers increased in multiple organs by 18 weeks of age. In sera from patients with DKD, 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 approximately 13% improvements in accuracy when serum metabolites were included to distinguish progression from early to advanced DKD stages.
Conclusion
Integrating synergistic biomarkers with serum metabolomics enhances the early detection of DKD, potentially improving outcomes by slowing disease progression in patients with T2DM.

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Diabetes Research and Clinical Practice.2026; 241: 113568. CrossRef

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.

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Do Not Replace Your Sugar, Simply Eat Less!
Jeehyun Lee, Sunghwan Suh
Diabetes & Metabolism Journal.2026; 50(1): 30. CrossRef
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Mohammad R. Monjur
Bangladesh Journal of Endocrinology and Metabolism.2026;[Epub] CrossRef
Associations of lifestyle behaviors with overweight and obesity: a cross-sectional study in Shenzhen, China
Shaojuan Zhao, Leyao Tang, Ni Xiong, Liping Liang, Xin Yin Wu, Chuanning Yu, Xueling Wei, Xuanzhen Wu, Wenjie Dai
Frontiers in Nutrition.2026;[Epub] CrossRef
Differential associations of beverage consumption with diabetic retinopathy: a systematic review and dose-response meta-analysis of observational studies
Siyan Liu, Xuan Wang, Guojun Chao, Wei Lu, Qi Wu, Yuxin Lv, Shuangshuang Yi, Zhengzheng Wu, Jing Yan
Frontiers in Medicine.2026;[Epub] CrossRef
Sugar rationing in the first 1000 days of life and risk of frailty: evidence from a natural experiment
Rui Zhang, Yuelan Gao, Hong Li, Yuhan Wei, Wanyang Zhong, Kai Tong, Zhibo Sun
The Journal of nutrition, health and aging.2026; 30(7): 100883. CrossRef
Influencing adolescents' beverage choices: An experimental study on the role of autonomy support and the availability of healthier options
Roselinde L. van Nee, Ellen van Kleef, Hans C.M. van Trijp
Appetite.2026; 226: 108618. CrossRef
Factors Influencing Water and Sweet Beverage Purchasing Decisions and Behaviours Among Low-Income Households in Four Peri-Urban Communities in Accra: An Exploratory Study
Christopher Delali Amegah, Gloria Adobea Odei Obeng-Amoako, Shu Wen Ng, Monica Lambon-Quayefio, Seth Adu-Afarwuah
International Journal of Environmental Research and Public Health.2026; 23(6): 799. CrossRef
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HyunJi Son, Khongorzul Ganbat, SuJin Song
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The oral und systemic health risks of sugar consumption: an umbrella review
J. P. Woelber, N. Wirth, A. Dallmer-Zerbe, C. Tennert
Clinical Oral Investigations.2026;[Epub] CrossRef

Pharmacotherapy
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; Diabetes Metab J. 2026;50(3):576-586. Published online December 19, 2025; DOI: https://doi.org/10.4093/dmj.2025.0528

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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.

Citations

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Revisiting GPR40 Agonist in Type 2 Diabetes Mellitus: A Cautious but Meaningful Return
Eun-Hee Cho
Diabetes & Metabolism Journal.2026; 50(3): 472. CrossRef

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; Diabetes Metab J. 2026;50(5):952-964. Published online December 15, 2025; DOI: https://doi.org/10.4093/dmj.2025.0477

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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=120 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; Diabetes Metab J. 2026;50(4):797-807. Published online December 9, 2025; DOI: https://doi.org/10.4093/dmj.2025.0557

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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.

Citations

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Global burden of type 2 diabetes attributable to dietary risks in working-age adults aged 25–64 years: insights from the GBD 2023 study
Xin Chen, Xiyue Xiong, Lawrence W.C. Chan, Changtao Hu, Sheng Li, Sijun Yang
Diabetes Research and Clinical Practice.2026; 240: 113521. CrossRef

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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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.

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Validation Performance of Screening Tools for Predicting Obstructive Sleep Apnea Among Chinese Patients Undergoing Metabolic Bariatric Surgery: Insights from a Multicenter Database
Lizhen Liu, Pei Tang, Joyce Wai-Ting Chiu, Zhiyong Dong, Cunchuan Wang, Weixin Huang, Wenhui Chen
Obesity Surgery.2026; 36(6): 3117. CrossRef
Explainable Machine-Learning Model for Predicting Severe Obstructive Sleep Apnea in Patients Undergoing Metabolic Bariatric Surgery
Wenhui Chen, Lili Li, Junsen Peng, Cunchuan Wang, Guie Gao, Zhiyong Dong
Obesity Surgery.2026; 36(8): 4334. CrossRef

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; Diabetes Metab J. 2026;50(3):565-575. Published online November 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0681

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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.

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Glucagon-like peptide-1 receptor agonists and tirzepatide are associated with reduced mortality, cardiovascular, and psychiatric risks in patients with hidradenitis suppurativa and type 2 diabetes and/or obesity: a retrospective cohort study
Inga C. Brouer, Aida Zani, Henning Olbrich, Ralf J. Ludwig, Diamant Thaçi
Frontiers in Medicine.2026;[Epub] CrossRef

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; Diabetes Metab J. 2026;50(3):535-551. Published online November 3, 2025; DOI: https://doi.org/10.4093/dmj.2025.0287

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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.

Citations

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β‐cell recovery revisited: Is prediabetes remission driven by insulin sensitivity or β‐cell function?
Joonyub Lee, Kun‐Ho Yoon
Journal of Diabetes Investigation.2026; 17(5): 716. CrossRef

Basic and Translational Research
4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects: Mengqin Tu, Xiaoli Zou, Xiaozhen Tan, Yijun Liu, Xinxu Ge, Yu Hu, Qiuyue Peng, Linlin Huang, Yan Zeng, Chunxia Jia, Man Guo, Jiao Chen, Yang Long, Yong Xu; Diabetes Metab J. 2026;50(4):707-723. Published online November 3, 2025; DOI: https://doi.org/10.4093/dmj.2024.0579; Correction in: Diabetes Metab J 2026;50(5):1020

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Background
Diabetic foot ulcers are a severe diabetic complication characterized by poor healing. Itaconate, a tricarboxylic acid cycle byproduct, has been shown to improve wound healing. This study investigated the potential of 4-octyl itaconate (4-OI), an esterified derivative of itaconate, to modulate efferocytosis and macrophage pro-resolving function to promote diabetic wound healing.
Methods
A diabetic mouse wound model was used. For in vitro analysis, RAW264.7 macrophages and apoptotic Jurkat cells were cocultured under high glucose conditions (HG, 30 mM). To further evaluate the roles of macrophages, monocarboxylate transporter 1 (MCT1), and lactate in 4-OI-promoted diabetic wound healing, we used clodronate-liposomes (CLD-Lipo) to deplete macrophages, AZD3965 as an MCT1 inhibitor, and telmisartan to validate our hypothesis.
Results
In diabetic mice, impaired clearance of apoptotic neutrophils and persistent M1 activation delayed wound healing. 4-OI improved diabetic wound repair by enhancing efferocytosis, shifting macrophages toward an M2 pro-resolving phenotype, and boosting angiogenesis. 4-OI showed a protective effect mediated by macrophages, while endothelial cells and neutrophils also played synergistic roles in diabetic wound healing. Moreover, 4-OI upregulated MCT1, which, in turn, increased the release of lactate triggered by efferocytosis at the wound site. Lastly, we confirmed that the pro-resolving effects of 4-OI onmacrophage function were mediated by promoting pro-resolving macrophage proliferation and polarization via efferocytosis-induced lactate release and subsequent activation of G protein-coupled receptor 132 (GPR132).
Conclusion
4-OI promotes diabetic wound healing through macrophage-dependent and macrophage-independent mechanisms. Moreover, the protective effect of 4-OI on macrophages was mediated through MCT1-mediated lactate release triggered by efferocytosis and subsequent GPR 132 activation.

Citations

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Roles of efferocytosis in wound repair: Process, cells, and signals
Yilin Sun, Haiying Guo, Yang Bai, Jin Chen, Yuhong Li
Genes & Diseases.2026; 13(3): 101937. CrossRef
4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects (Diabetes Metab J 2026;50:707-23)
Muhammad Junaid, Yabin Zhu
Diabetes & Metabolism Journal.2026; 50(4): 818. CrossRef
Efferocytosis: unifying pathogenic hub in metabolic disorders—mechanistic landscapes, targeted therapies and translational bottlenecks
Dongze Li, Yao Huang, Xuanqin Chen, Li Zhang, Qiming Gong, Qifu Li, Yu Li, Yong Xu, Wei Huang
Frontiers in Immunology.2026;[Epub] CrossRef
Diosgenin presents a novel role in promoting diabetic wound healing: A mechanism involving Sirt6/Nrf2-mediated inhibition of ferroptosis
Ji-qi Wang, Lu Chen, Yu-zhe Lin, Xiu-zhi Zhang, Yi-tian Yu, Yi-han Lin, Li-jiang Han, Yi-yun Lv, Nai-feng Tian, Zhen Lin, Wei-jun Guo
Journal of Pharmaceutical Analysis.2026; 16(8): 101635. CrossRef
Niche-dependent immunometabolic regulation of tissue repair and regeneration
Xinchen Xie, Lingbin Zeng, Zhexu Chi, Di Wang
Immunity & Inflammation.2026;[Epub] CrossRef
Progress on hydrogel delivery systems targeting metabolism disorders in the treatment of diabetic foot ulcers
Shihua Liu, Lixian Huang, Hong Dong
Frontiers in Cell and Developmental Biology.2026;[Epub] CrossRef

Reviews

Guideline/Statement/Fact Sheet
Bridging Evidence and Practice: A Consensus Statement from the Korean Diabetes Association on Diabetes Screening, Pharmacological Treatment and Severe Diabetes: Jong Han Choi, Shinae Kang, Soo-Kyung Kim, Won Jun Kim, Ji Min Kim, Jaehyun Bae, Jae-Seung Yun, Eonju Jeon, Young-Eun Kim, Jae Hyun Bae, Hun Jee Choe, Young Min Cho, Seung-Hyun Ko, Sang Yong Kim, Hae Jin Kim, You-Cheol Hwang, Min Kyong Moon, Suk Chon, Seon Mee Kang, Hyuk-Sang Kwon, Mi Kyung Kim, You-Bin Lee, Se Hee Min, Jung Hwan Park, Woo Je Lee, Bong-Soo Cha, Byung-Wan Lee; Diabetes Metab J. 2025;49(6):1155-1177. Published online November 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0978

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This Korean Diabetes Association (KDA) consensus statement bridges global evidence with the Korean clinical context, where large randomized and real-world data remain limited. Recommendations required ≥80% agreement by the committee of clinical practice guideline and approval by the board of directors. The statement comprises three domains: diabetes screening aligned with Korean epidemiology; pharmacologic management guided by pathophysiology and comorbidities; and a severity construct of “severe diabetes mellitus” that links complication-based staging with metabolic grading to match therapeutic intensity to disease complexity. Compared with prior KDA guidelines, this statement introduces substantive advances in three areas. First, screening recommendations are streamlined to emphasize risk-aligned, practical implementation rather than prescriptive test sequences. Second, pharmacologic management applies an individualized framework for drug selection that jointly considers pathophysiology and comorbidities. It operationalizes individualized selection by dominant pathophysiology (insulin resistance vs. insulin insufficiency) and coexisting conditions, and formalizes treatment dynamics—early combination, timely initiation of injectables, avoidance of overbasalization, and structured deintensification. It also prioritizes agents with proven cardiovascular and renal protection and elevates management of obesity and metabolic dysfunction-associated steatotic liver disease as central goals; clinically, insulin should be initiated promptly in hypercatabolic states or suspected islet failure, and technology-enabled care—including continuous glucose monitoring and automated insulin delivery—are integral across all stages. Third, the newly introduced severity construct underpins treatment-intensity decisions across domains without reiterating prescriptive algorithms. Collectively, these recommendations provide a coherent, context-appropriate framework for diabetes screening and management in Korea and identify priorities for future evidence generation.

Citations

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Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2026; 28(4): 3305. CrossRef
Efficacy and safety of anagliptin added to metformin and empagliflozin 25 mg in patients with type 2 diabetes: a 24-week randomized, double-blind, placebo-controlled phase 3 trial with 28-week open-label extension
Jun Sung Moon, Kyung-Ah Han, Jae Myung Yu, Jong Chul Won, Jun Goo Kang, Soojin Park, Cheol-Young Park
Diabetes Research and Clinical Practice.2026; 236: 113272. CrossRef
Cardiometabolic 2.0: Redefining Cardiovascular Prevention Through SGLT-2 Inhibitors and GLP-1 Receptor Agonists
Maria-Daniela Tanasescu, Andrei-Mihnea Rosu, Alexandru Minca, Maria-Mihaela Grigorie, Delia Timofte, Dorin Ionescu
Life.2026; 16(5): 756. CrossRef
Contemporary Type 2 Diabetes Guidelines: Converging Evidence, Diverging Strategies, and the Position of the Korean Diabetes Association Framework
Suk Kyeong Kim, Dong-Lim Kim, Keeho Song, Shinae Kang, Byung-Wan Lee, Jong Han Choi
Endocrinology and Metabolism.2026; 41(3): 351. CrossRef
The effect of rapid improvement of blood glucose level on diabetic neuropathy in Korean people with diabetes mellitus
Hun Jee Choe, Bo Kyung Koo, Yoon-Ho Hong, Nam Hoon Kim, Jun Sung Moon, Yong-ho Lee, Ho Chan Cho, Soo Heon Kwak, Soo Lim, Dong-Lim Kim, Tae Ho Kim, Sin Gon Kim, Min Kyong Moon
Diabetes Research and Clinical Practice.2026; 238: 113388. CrossRef
Periodontal Procedure Intensity and Incident Tinnitus in Korean Adults: A Nationwide Cohort Study
Yu-Rin Kim, Minkook Son, Seon-Rye Kim, Byung-Jun Cho
Medicina.2026; 62(8): 1578. CrossRef

Lifestyle and Behavioral Interventions
Optimizing Physical Activity Strategies for Older Adults with Diabetes: Hyeon-Jin Yu, Doyoun Hong, Kyuho Kim, Ji Hye Heo, Dong-Hyeok Cho, Yoshitaka Hashimoto, Jae-Seung Yun; Diabetes Metab J. 2025;49(6):1178-1197. Published online November 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0967

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The increasing prevalence of diabetes among older adults has emerged as a major socioeconomic burden. This population is highly heterogeneous, ranging from functionally independent to severely impaired individuals, making it difficult to establish standardized recommendations. Physical activity (PA) is a cornerstone of diabetes management; however, current exercise guidelines do not adequately address the wide spectrum of functional capacities observed in older adults. For those with physical limitations, relatively simple activities such as walking, breaking up sedentary time, incorporating movement into daily routines, and aquatic exercise have been proposed, yet supporting evidence remains limited. This review summarizes the pathophysiologic mechanisms of metabolic and functional changes associated with aging and diabetes—including sarcopenia, altered body composition, and cardiovascular decline—and comprehensively discusses the benefits and precautions of various exercise modalities, tailored recommendations according to diabetes-related complications, and key clinical considerations. We further classified older adults with diabetes into three functional levels, individuals in good health, those with some comorbidities or mild disabilities, and those with high comorbidities and/or functional impairment, and proposed corresponding physical activity strategies for each level. Finally, we highlight practical and feasible approaches, including walking, interrupting sedentary behavior, daily functional movements, and aquatic exercise, to enhance clinical applicability for individuals with reduced physical capacity. These tailored, function-based strategies may help older adults with diabetes achieve safer, more effective, and sustainable improvements in glycemic control and overall health.

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Predictors of Adherence to Physical Activity Among Adults with Diabetes
Amil Kusain Tan, Ajatshatru Pathak, Shiela M. Strauss
The Journal for Nurse Practitioners.2026; 22(6): 105778. CrossRef
Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics
Shibo Wei, Soyeon Shin, Dongryeol Ryu, Chang-Myung Oh
Diabetes & Metabolism Journal.2026; 50(5): 825. CrossRef
Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies
Ji Yoon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2026; 50(5): 844. CrossRef

Guideline/Statement/Fact Sheet
Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications: Jae Hyun Bae, Hun Jee Choe, Ye Seul Yang, Mi Hae Seo, Jong Han Choi, Gyuri Kim, Young Sang Lyu, Jeung Hun Han, Shinae Kang, Won Jun Kim, Kyung-Soo Kim, Young Min Cho, Bong Soo Cha, for the Severe Diabetes Mellitus Task Force of the Korean Diabetes Association; Diabetes Metab J. 2025;49(6):1141-1154. Published online October 28, 2025; DOI: https://doi.org/10.4093/dmj.2025.0739

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Diabetes mellitus comprises a heterogeneous group of metabolic disorders differing in etiology, clinical course, and outcomes. Traditional classifications, such as type 1 and type 2 diabetes mellitus, fail to capture the full heterogeneity, including variation in insulin deficiency, insulin resistance, and complication burden. To address these limitations, we propose the Diabetes Grade–Stage Classification, an integrated system that combines pathophysiology-based grading with complication-based staging. Grading quantifies metabolic dysfunction through the assessment of insulin deficiency and insulin resistance. In parallel, staging assesses the extent of target organ damage, particularly in the cardiovascular, renal, ocular, and nervous systems. Together, this framework enables a comprehensive assessment of disease status, identification of vulnerable or high-risk phenotypes, and implementation of risk-adapted management strategies. Clinically, it facilitates personalized care, promotes collaborative coordination, and strengthens physician–patient communication. Furthermore, this framework provides a scalable structure for integrating disease severity into both individual- and population-level interventions. Although the current criteria for grading and staging are based on expert consensus and selected clinical indicators, such as low C-peptide levels and advanced complications, further validation and refinement are needed. In conclusion, the grading and staging system provides an operational tool for classifying the severity of diabetes mellitus and has the potential to extend life expectancy and improve quality of life for people living with diabetes mellitus.

Citations

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Material-driven glucose responsiveness in insulin delivery systems: carrier selection and performance
Zhihan Li, Jingge Jiang, Ziyu Zhu, Cheng Luo, Chunyi Xu, Chuanpin Chen, Guoqin Ren, Ruofei Huang, Dongjuan He
Frontiers in Endocrinology.2026;[Epub] CrossRef
Circulating GDF15 levels reflect metabolic and inflammatory burden in early dysglycemia: findings from the ADIOS cohort
Ji Yoon Kim, Ah Hyeon Lee, Jiyoon Lee, Hye-Min Jang, Sin Gon Kim, Dong-Hoon Kim, Nam Hoon Kim
Diabetes Research and Clinical Practice.2026; 239: 113461. CrossRef
Diabetes progression and severe hypoglycemia: a nationwide cohort study of 2,475,605 adults with type 2 diabetes mellitus
Kyu-Na Lee, Bongseong Kim, Mee Kyoung Kim, Sukil Kim
The Korean Journal of Internal Medicine.2026; 41(5): 916. CrossRef
Bridging Evidence and Practice: A Consensus Statement from the Korean Diabetes Association on Diabetes Screening, Pharmacological Treatment and Severe Diabetes
Jong Han Choi, Shinae Kang, Soo-Kyung Kim, Won Jun Kim, Ji Min Kim, Jaehyun Bae, Jae-Seung Yun, Eonju Jeon, Young-Eun Kim, Jae Hyun Bae, Hun Jee Choe, Young Min Cho, Seung-Hyun Ko, Sang Yong Kim, Hae Jin Kim, You-Cheol Hwang, Min Kyong Moon, Suk Chon, Seo
Diabetes & Metabolism Journal.2025; 49(6): 1155. CrossRef

Original Articles

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
Identification and functional validation of EPS15L1 as a key driver of triple-negative breast cancer
Chun-Chao Wang, Sabareeswaran Krishnan, Yen-Hsun Wang, Kai-Chen Hsu, Tzu-Sheng Hsu, Chung-Hsing Chen, Shang-Hung Chen, Ren-Hua Chung
npj Breast Cancer.2026;[Epub] 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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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.

Citations

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Efficacy and Safety of Pioglitazone Added to Metformin and SGLT2 Inhibitors in Type 2 Diabetes: An Updated Systematic Review and Meta-analysis
Syed Ibad Hussain, Amna Amir Jalal, Zahabia Adnan, Shanza Shakir, Devya Khaim Chandani, Muhammad Ali Makhdoom
Annals of Pharmacotherapy.2026;[Epub] CrossRef
Bioequivalence of Fixed-Dose Dapagliflozin-Pioglitazone in Healthy Indian Adults: Results From the Randomized Crossover PRO-4 Study
J. Hari Prasath, Umesh Garg, Kalyan Kurapati, Abhamoni Baro Agarwal, Parul Singhal, Thamburaj Anthuvan, Smriti Gadia, Amit Gupta, Sridhar S B.
Cureus.2026;[Epub] CrossRef

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; Diabetes Metab J. 2026;50(3):599-611. Published online October 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0200; Correction in: https://doi.org/

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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.

Cardiovascular Risk/Epidemiology
Association of Remnant Cholesterol Inflammation Index with Cardiovascular Risks and All-Cause Mortality in Individuals with Diabetes or Prediabetes: Qi-Lin Ma, Lei-Lei Du, Jia Peng; Diabetes Metab J. 2026;50(3):587-598. Published online October 2, 2025; DOI: https://doi.org/10.4093/dmj.2025.0305

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Background
Remnant cholesterol (RC) and low-grade inflammation are established contributors to cardiovascular disease (CVD) risks in diabetes. However, their combined prognostic impact remains unclear in dysglycemia. We evaluated the remnant cholesterol inflammation index (RCII), integrating RC and high-sensitivity C-reactive protein (hsCRP), for predicting mortality and CVD risks in diabetes/prediabetes.
Methods
This study included 2206 United States adults with diabetes/prediabetes from National Health and Nutrition Examination Survey 2015–2018. RCII was calculated as [RC (mg/dL)×hsCRP (mg/L)]/10. All-cause mortality was tracked via National Death Index until 2019; CVD risk was assessed cross-sectionally. Cox proportional hazard regression determined the hazard ratio (HR) and 95% confidence intervals (CIs) of RCII for all-cause mortality. Logistic regression models estimated the odds ratio (OR) and 95% CIs of RCII for CVD risks.
Results
For CVD risks, Q4 vs. Q1 demonstrated increased odds (OR, 2.32; 95% CI, 1.23 to 4.37), though per-standard deviation (SD) increments were non-significant (OR, 1.15; 95% CI, 0.98 to 1.35; P=0.083). During a median of 38 months follow-up, higher RCII quartiles showed graded associations with all-cause mortality (Q4 vs. Q1: HR, 2.45; 95% CI, 1.08 to 5.58; per 1-SD increase: HR, 1.21; 95% CI, 1.08 to 1.35). Restricted cubic splines confirmed dose-dependent relationships for CVD risks and all-cause mortality (all P=0.005 for overall). Subgroup analyses revealed consistent mortality associations but sex-specific CVD interactions (P=0.047 for interaction).
Conclusion
Our study found the RCII as a biomarker for predicting all-cause mortality and CVD risks in individuals with prediabetes or diabetes, highlighting the synergistic effects of RC and low-grade inflammation on adverse outcomes in this population and may facilitate early identification of individuals at heightened risk for CVD.

Citations

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Association of remnant cholesterol inflammation index with future cardiovascular disease risk in patients with cardiovascular-kidney-metabolic syndrome stages 0–3
Nanshan Xie, Lihuan Zeng, Xiangming Hu, Zejia Wu, Weiling Lu, Songyuan Luo, Jianfang Luo
Diabetes Research and Clinical Practice.2026; 233: 113146. CrossRef
Association Between the Remnant Cholesterol Inflammation Index and Cardiac Syndrome X
İbrahim Aktaş, Erdoğan Yaşar, Kadir Uçkaç
Diagnostics.2026; 16(8): 1113. CrossRef
Remnant cholesterol inflammation index as a predictor of mortality in patients with acute decompensated heart failure: evidence from the Jiangxi, China cohort
Guoan Jian, Zhenyu Wang, Juan Wang, Houhui Lan, Kun Jiang, Zihao Lu, Guotai Sheng, Guobo Xie, Wei Wang, Yang Zou, Chunyuan Jiang
Frontiers in Endocrinology.2026;[Epub] CrossRef
Longitudinal Trajectories and Cumulative Burden of Remnant Cholesterol Inflammatory Index and Mortality Risk
Yebin Lan, Yehui Lan, Shuaiqing Chen, Shan Tan, Yami Jiang, Mingshen Lin
Geriatrics & Gerontology International.2026;[Epub] CrossRef
The Relationship Between the Remnant Cholesterol Inflammation Index and Coronary Collateral Circulation in Patients with Chronic Total Occlusion
Erdoğan Yaşar, İbrahim Aktaş, Tolga Çakmak, Furkan Ay
Journal of Clinical Medicine.2026; 15(19): 7352. CrossRef
Cumulative exposure to the remnant cholesterol inflammation index and incident diabetes mellitus in middle-aged and elderly Chinese adults
Lianguang Xie, Xuan Zhou, Chun Yao, Diankui Shui
Medicine.2026; 105(41): e51063. CrossRef

Basic and Translational Research
PUM2 Lowers HDAC9 mRNA Stability to Improve Contrast-Induced Acute Kidney Injury by Attenuating Oxidative Stress and Promoting Autophagy: Wei Chen, Hengcheng Lu, Wenni Dai, Hao Li, Yinyin Chen, Guoyong Liu, Liyu He; Diabetes Metab J. 2026;50(4):672-687. Published online September 10, 2025; DOI: https://doi.org/10.4093/dmj.2024.0396

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Background
Contrast-induced acute kidney injury (CIAKI) is the third leading cause of hospital-acquired acute kidney injury and diabetes mellitus (DM) has been identified as a risk factor for CIAKI. However, the molecular mechanism underlying DM-CIAKI remains unclear and requires further investigation.
Methods
Mouse and cell models of DM-CIAKI were established. Kidney function was evaluated by measuring biochemical indicators and using hematoxylin and eosin staining. Gene and protein abundance was assessed using real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting. Glutathione peroxidase, superoxide dismutase, and malondialdehyde were measured using commercial kits, and reactive oxygen species were detected using a dihydroethidium (DHE) probe and the 2ʹ,7ʹ-dichlorofluorescein diacetate (DCFH-DA) method. Apoptosis in tissues and cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cell viability and proliferation were measured using Cell Counting Kit-8 and 5-ethynyl-2ʹ-deoxyuridine (EdU) assays. The interaction between pumilio RNA binding family member 2 (PUM2) and histone deacetylase 9 (HDAC9) was validated using RNA immunoprecipitation (RIP) and RNA pull-down assays.
Results
PUM2 expression was markedly reduced in DM-CIAKI models, whereas HDAC9 expression was notably increased. Subsequently, PUM2 silencing aggravated kidney injury in DM-CIAKI mice by enhancing oxidative stress and suppressing autophagy, whereas HDAC9 inhibition or HDAC9 silencing had the opposite effects. Mechanistically, PUM2 could suppressed the stability of HDAC9 mRNA, thereby attenuating HDAC9 expression. Furthermore, HDAC9 overexpression abolished PUM2 overexpression-mediated inhibition of oxidative stress and promotion of autophagy in high glucose- and contrast media-treated human kidney-2 (HK-2) cells.
Conclusion
PUM2 overexpression suppressed oxidative stress and promoted autophagy to alleviate renal injury in DM-CIAKI by interacting with HDAC9 mRNA, which mediated HDAC9 and mRNA degradation and inhibited HDAC9 expression.

Citations

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Purpurin Rescues Contrast-Induced Acute Rat Kidney Injury via Inducing Autophagy and Inhibiting Apoptosis
Kangxu He, Xiaoying Sun, Xinhui Pan, Xiaoda Yang, Qi Wang, Kai Liao
Pharmaceuticals.2026; 19(1): 116. CrossRef
Rubia cordifolia L. Dichloromethane Extract Ameliorates Contrast-Induced Acute Kidney Injury by Activating Autophagy via the LC3B/p62 Axis
Xiaoying Sun, Kangxu He, Guanzhong Chen, Xiaoda Yang, Xinhui Pan, Kai Liao
Molecules.2026; 31(2): 316. CrossRef
Research progress on risk factors and early predictors of contrast-induced nephropathy
Yemei Ma
American Journal of Translational Research.2026; 18(4): 2795. CrossRef

Basic and Translational Research
Pancreatic Islet Transplantation in Extrahepatic Sites: Evaluation of the Venous Sac in Large Mammal Models: Giorgi Kenchadze, Ivane Abiatari, Antonello Pileggi, Norma S. Kenyon, Dora M Berman, R. Damaris Molano, Konstantine Gogichaishvili, Revaz Otarashvili, Anzor Tchavtchavadze, Teona Midelashvili, Mariam Motsikulashvili, Camillo Ricordi, Thierry Berney, Ekaterine Berishvili; Diabetes Metab J. 2026;50(3):495-505. Published online September 8, 2025; DOI: https://doi.org/10.4093/dmj.2024.0400

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Abstract PDF PubReader ePub: Background
The long-term clinical efficacy of intraportal islet transplantation is hampered by islet loss due to inflammation, oxidative stress, and insufficient vascularization. This study explores the venous sac as an alternative implantation site for islet transplantation in large animal models.
Methods
An immunosuppressed, diabetic cynomolgus monkey received allogeneic islet implants in its mesenteric venous sac, with metabolic assessments over 112 days. Dogs underwent islet autotransplantation into various venous sacs, with their glycemic control and other metabolic parameters monitored for 1 month.
Results
In a nonhuman primate, the mesenteric venous sac site improved glycemic control over a 3-month period, followed by destabilization of graft function. Histological studies revealed healthy islets. The lack of mononuclear cell infiltrate suggested no signs of graft rejection. Saphenous venous sacs in dogs showed superior glycemic control, reduced insulin requirements, and maintained C-peptide levels, comparable to intraportal transplantation. Histological analyses confirmed islet preservation and graft vascularization in saphenous venous sacs.
Conclusion
This study provides preclinical evidence in support of the venous sac as a valuable extrahepatic location for pancreatic islet implantation. We found that the saphenous vein is a more effective site for islet engraftment than the mesenteric vein. This study offers potential benefits for improving the success rates of clinical islet transplantation.

Cardiovascular Risk/Epidemiology
High Waist-to-Height Ratio Increases the Risk of Cardiovascular Outcomes in Adults with Type 1 Diabetes Mellitus: A Nationwide Cohort Study: Kyeong-Jin Kim, Seohyun Kim, Rosa Oh, So Hyun Cho, Myunghwa Jang, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Ji Yoon Kim, Jae Hyeon Kim; Diabetes Metab J. 2026;50(4):739-751. Published online September 4, 2025; DOI: https://doi.org/10.4093/dmj.2025.0179

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Background
Central obesity contributes to an increased risk of cardiovascular disease (CVD) and mortality. The waist-to-height ratio (WHtR) is a practical marker of central obesity across sexes, ages, and ethnicities. However, its association with comprehensive cardiovascular (CV) outcomes in patients with type 1 diabetes mellitus (T1DM) remains unclear.
Methods
From a nationwide cohort database (2006–2020), 16,928 Korean adults with T1DM were included. Participants were categorized according to WHtR using three criteria: a three-group classification (<0.5, 0.5 to <0.6, and ≥0.6) and two binary classifications (≥0.5 vs. <0.5; ≥0.6 vs. <0.6). The primary outcome was a composite CV event, including heart failure (HF), myocardial infarction (MI), ischemic stroke, and CVD-related death, with each component analyzed as a secondary outcome.
Results
During a median follow-up of 6.7 years (interquartile range, 5.2 to 8.8), 4,293 composite CV events occurred. Compared with the WHtR <0.5 group, the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the composite CV outcome were 1.14 (1.05 to 1.24) in the WHtR 0.5 to <0.6 group and 1.62 (1.38 to 1.90) in the WHtR ≥0.6 group (P for trend <0.001). Increasing trends in aHRs were noted with rising WHtR values for each component of the composite outcome. Compared with the WHtR <0.6 group, the aHRs for the WHtR ≥0.6 group were as follows: HF, 1.49 (95% CI, 1.28 to 1.73); MI, 1.31 (95% CI, 1.02 to 1.68); ischemic stroke, 1.24 (95% CI, 1.02 to 1.51); and CVD-related death, 2.09 (95% CI, 1.49 to 2.92).
Conclusion
High WHtR was associated with an increased risk of CV events in adults with T1DM.

Citations

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A CVD Classification Model for Individuals With Obesity: Multi‐Ethnic Validation Based on Multiple Metabolic Indicators
Runmin Cao, Yurun Zhang, Ling Cao, Honghe Jiang
Obesity.2026; 34(9): 1806. CrossRef

Brief Report

Technology/Device
Effectiveness of the Stage 4 Smart Insulin Pen DIA:CONN P8 for Glycemic Control in a Real-World Setting: So Yoon Kwon, Hyoseon Kwak, Jae Hyeon Kim; Diabetes Metab J. 2026;50(3):612-617. Published online September 3, 2025; DOI: https://doi.org/10.4093/dmj.2025.0112

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This study evaluated whether a stage 4 smart insulin pen (SIP) provides superior glycemic control compared with a traditional insulin pen (TIP) in individuals with intensively insulin-treated diabetes. Forty-two adults with continuous glucose monitoring (CGM), multiple daily insulin injections, and no prior SIP use were included. After diabetes self-management education (DSME), the SIP group (n=21) initiated SIP, whereas the TIP group (n=21) continued their usual regimens. Glycemic metrics were assessed using CGM before and 2 weeks after DSME. Both groups demonstrated significant improvements in glycemic outcomes. However, SIP users exhibited superior improvements in the percentage of time in range, percentage of time below range (%TBR) <70 mg/dL, %TBR <54 mg/dL, and glycemic risk index compared with TIP users (between-group difference [BD] 11.0%, P=0.046; BD –2.6%, P=0.024; BD –0.9%, P=0.027; BD –18.2, P=0.022, respectively). These findings suggest that SIP, with its bolus calculation and CGM integration, is associated with improved glycemic outcomes in adults with intensively insulin-treated diabetes.

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Technology in Diabetes: A Year in Review
Subhankar Chatterjee, Subhodip Pramanik, Nitin Kapoor, Sanjay Kalra
Diabetes Therapy.2026; 17(6): 823. CrossRef
Retrospective Validation of a Stage 5 Decision Support Algorithm Using Clinical Trial Data From Stage 4 Smart Insulin Pens
Jee Hee Yoo, Seohyun Kim, Younghoon Kim, Sang-Man Jin, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2026;[Epub] CrossRef
Insulin pens and the digital ecosystem
Johan Jendle, Peter Adolfsson, Roque Cardona-Hernandez, Laurent Crenier, Sergio Di Molfetta, Dominic Ehrmann, Francesco Giorgino, Martin Haluzik, Irl B. Hirsch, Concetta Irace, Amy Jolley, David C. Klonoff, Jens Kröger, Julia K. Mader, Kirsten Nørgaard, J
Diabetologia.2026;[Epub] CrossRef

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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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.

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The Triangular Interaction Between Dietary Polyphenols, Gut Microbiota and Type 2 Diabetes
Emily Bayliss, Landri Shope, Seth Woodfin, Gretchka Mair, Matthew H. Becker, William Moore
International Journal of Molecular Sciences.2026; 27(11): 4782. CrossRef

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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Jiaqi Li, Guishao Tang, Zhiguo Xie, Lin Yang, Zhiguang Zhou, Keyu Guo
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Redefining β-Cell Function in Type 2 Diabetes Mellitus: From Comprehensive Assessment to Precision Medicine
YongKyung Kim, Joon Ha, Jun Sung Moon
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Correlation between TyG index, TyG-BMI index and AIP index and early-onset type 2 diabetic nephropathy
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Diabetic Medicine.2026;[Epub] CrossRef
Psychosocial care and experiences in young adults living with early‐onset type 2 diabetes: A narrative review
Molly Caba, Márcia Carvalho, Angus Forbes, Rita Forde, Kirandip Gill, Mohsin Khalifa, Judith Parsons, Jane Speight, Paula M. Trief, Michelle Hadjiconstantinou
Diabetic Medicine.2026;[Epub] CrossRef
Digital Management of Early-Onset Type 2 Diabetes: Empowerment, Challenges, and Future Outlook
Li-Jun Guo, Kah-Seng Low, Sok-Kun Tae, Lee-Ling Lim
Current Diabetes Reports.2026;[Epub] 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; Diabetes Metab J. 2026;50(4):808-815. Published online September 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0077

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Background
Type 2 diabetes mellitus (T2DM) is common among older adults and may increase the risk of sarcopenia and frailty. This study evaluated 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. Following the guidelines set by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), 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 sarcopenia, isolated frailty, both conditions (sarcopenia and frailty), or neither.
Results
The median age of the patients was 69 years, and 71.6% were female. Isolated sarcopenia was present in 11.0% of patients, isolated frailty in 22.4%, and both sarcopenia and frailty in 9.8%. After adjustment for age, sex, comorbidities, activities of daily living, glycemic control, and nutritional status, sarcopenia and frailty were significantly associated with an increased risk of 5-year mortality. Isolated frailty also significantly predicted mortality (hazard ratio, 2.59; 95% confidence interval, 1.34 to 5.03; P=0.005).
Conclusion
Sarcopenia and frailty were significant predictors of increased mortality risk in older adults with T2DM. Coexisting sarcopenia and frailty posed the highest risk. Early identification and targeted interventions for these conditions in older patients with T2DM are crucial to improving outcomes.

Citations

Citations to this article as recorded by

Sarcopenia and Mortality, Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis
Juan Du, Xiaoyu Shu, Taiping Lin, Hualong Liao, Liying Zhang, Jirong Yue
Endocrine Practice.2026;[Epub] CrossRef
The impact of sarcopenia on clinical outcomes in patients with diabetes: A systematic review and meta-analysis of cohort studies
Ying Tang, Wenyuan Li, Linling Wu, Yunhang Wang, Nini Shi, Jianxun Cao, Jie Zheng, Sujie Shi, Yuxia Ma
Primary Care Diabetes.2026; 20(3): 264. CrossRef
Overlap between body mass index- and height-adjusted sarcopenic obesity and their association with functional capacity in older adults with diabetes: A study based on the JWGSO consensus
Satoshi Ida, Kanako Imataka, Tatsuya Tanaka, Kazuya Murata
Endocrine.2026;[Epub] CrossRef
Reciprocal risks of diabetes and sarcopenia in aging Chinese adults: A prospective cohort study using a semi-Markov multi-state framework
Yirui Chen, Yinuo Qu, Siyi Kong, Tianyun Wang, Zhiyuan Liu, Huixia Ren, Kai Ma, Tieniu Zhao, Hongwu Wang, Mengyang Wang
Medicine.2026; 105(26): e49398. CrossRef
Sarcopenia and Frailty in Type 2 Diabetes Mellitus: An Overlooked Challenge
Chul-Hee Kim
Diabetes & Metabolism Journal.2026; 50(4): 666. CrossRef
Mitochondrial Proteostasis Links Diabetes and Sarcopenia: Cross-Scale Convergence from Experimental Models to Human Multi-Omics
Shibo Wei, Soyeon Shin, Dongryeol Ryu, Chang-Myung Oh
Diabetes & Metabolism Journal.2026; 50(5): 825. CrossRef

Basic and Translational Research
E2F5 Accelerates Vascular Smooth Muscle Cells Phenotype Switching in Diabetic Atherosclerosis through Activating Wnt/β-Catenin Pathway: Mingxue Di, Jie Wang, Lin Sun, Guang Yang, Qun Xu; Diabetes Metab J. 2026;50(3):506-518. Published online September 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0588

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Background
We determined the precise function of E2F transcription factor 5 (E2F5) on the development of diabetic atherosclerosis (DAS) and the underlying mechanisms.
Methods
Apolipoprotein E-knockout mice were intraperitoneally injected with streptozotocin for 5 days and fed a high-fat diet for 12 weeks for establishing an in vivo DAS model. To establish a DAS vascular smooth muscle cells (VSMCs) model, VSMCs were stimulated with fresh medium containing glucose and oxidized low-density lipoprotein. After the final treatment, serum lipids were detected, and aorta tissues were collected for hematoxylin and eosin staining, Western blot, Oil red O staining, and quantitative reverse transcription polymerase chain reaction. The effect of E2F5 on the proliferation, migration, cell cycle, phenotype switching, and cell cycle-related markers of VSMCs were evaluated.
Results
In vivo, the expression of E2F5 was elevated in aortic tissues of DAS mice. The downregulation of E2F5 alleviated the symptoms of DAS in mice. Moreover, E2F5 downregulation inhibited the phenotypic transformation of VSMCs in DAS mice. In vitro, the knockdown of E2F5 inhibited the phenotypic transformation of VSMCs. CyclinE overexpression reversed the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs. Additionally, we also found that the treatment of BML-284 significantly attenuated the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs.
Conclusion
E2F5 is an injurious factor in the pathogenesis of DAS, and the downregulation of E2F5 could repress VSMCs phenotype switching through inactivating Wnt/β-catenin pathway, and ultimately inhibit the progression of DAS.

Citations

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Metabolic memory failure and the reprogramming of atherosclerosis in diabetes
M. Devi, S. Evelyn Sharon, N. Harikrishnan, N. Pavithra, L. Shakthi
Obesity Medicine.2026; 61: 100703. CrossRef
E2F5 Promotes Vascular Endothelial Cell Proliferation and Angiogenesis in Diabetic Lower Limb Ischemia via an Autophagy-Related Mechanism
Yuyan Zhan, Hongwei Shi, Xiaoying Miu, Xiaoping Peng, Jungang Nie, Dong Liu, Qiong Duan, Ting Kang
Circulation Journal.2026; 90(10): 1425. CrossRef
SPI1 Promotes Intracranial Aneurysm Formation by Inhibiting Wnt5a Transcription
ZengShi Li, WeiChen Wang, Wei Li, Jie Peng, JunXi Liu, Yi Wu
Frontiers in Bioscience-Landmark.2026;[Epub] CrossRef
Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies
Qian Gong, Wei Zhao, Jing Xia, Zhiwei Nie, Ruifan Luo, Lingxiu Li, Changwu Dong, Yujiao Zheng
Frontiers in Immunology.2026;[Epub] CrossRef

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