Wu JY, Lee KW, Huang SC
… +2 more, Chang HY, Lin YM
Diabetes Res Clin Pract
· 2026 Jun · PMID 42009260
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BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome represents a progressive disease continuum linking metabolic risk factors with cardiovascular and kidney disease. Patients in early CKM stages (stages 1-2) repre...BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome represents a progressive disease continuum linking metabolic risk factors with cardiovascular and kidney disease. Patients in early CKM stages (stages 1-2) represent a critical therapeutic window; however, comparative evidence on pharmacologic strategies to prevent progression to advanced CKM stages remains limited. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has demonstrated superior metabolic efficacy compared with conventional GLP-1 receptor agonists (GLP-1 RAs), but its impact on CKM stage progression in real-world practice is unknown. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (January 2022-September 2025). Adults with CKM stage 1 or 2 who newly initiated tirzepatide or another GLP-1 RA were identified. A new-user design with 1:1 propensity score matching was applied to balance demographic characteristics, comorbidities, medications, and laboratory parameters. The primary outcome was progression to CKM stage 3 or 4, defined by incident heart failure, coronary artery disease, ischemic stroke, atrial fibrillation, peripheral artery disease, or very high-risk chronic kidney disease. Secondary outcomes included major adverse cardiovascular events (MACE), individual cardiovascular outcomes, and all-cause mortality. Hazard ratios (HRs) were estimated to use Cox proportional hazards models with one-year follow-up. RESULTS: After matching, 448,591 patients were included in each group. During follow-up, progression to CKM stage 3-4 occurred in 2.2% of patients receiving tirzepatide and 3.3% receiving GLP-1 RAs (HR 0.88, 95% CI 0.86-0.91; P<0.001). Tirzepatide was also associated with lower risks of MACE (HR 0.85, 95% CI 0.80-0.89), coronary artery disease, peripheral artery disease, ischemic stroke, heart failure, very high-risk chronic kidney disease, and all-cause mortality. No significant difference was observed for atrial fibrillation. Associations were consistent across prespecified subgroups, including age, sex, baseline CKM stage, obesity status, and statin use. CONCLUSIONS: In this large real-world cohort of patients with early-stage CKM syndrome, initiation of tirzepatide was associated with a lower risk of progression from CKM stages 1-2 to stages 3-4 compared with other GLP-1 RAs, along with consistent reductions in multiple cardiovascular outcomes. These findings suggest that therapeutic choices made earlier along the CKM continuum may be associated with early differences in disease trajectories, although longer-term studies are needed to determine their sustained clinical impact.
Hasebe M, Radha V, Amutha A
… +7 more, Tanaka D, Imaizumi T, Yabe D, Yoshiji S, Inagaki N, Mohan V, PAN INDIA Monogenic Study Collaborators Group and Japan Diabetes Society Monogenic Diabetes Committee
Diabetes Res Clin Pract
· 2026 Jun · PMID 42009259
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Nationwide cohorts from Japan and India show monogenic diabetes is present in a considerable proportion of young, non-obese individuals with diabetes. Clinical presentations are heterogeneous; notably, only up to ∼ 70% o...Nationwide cohorts from Japan and India show monogenic diabetes is present in a considerable proportion of young, non-obese individuals with diabetes. Clinical presentations are heterogeneous; notably, only up to ∼ 70% of cases had three-generation family history. These findings call for broader genetic testing in Asia beyond classical clinical screening criteria.
Boccatonda A, D'Ardes D, Brighenti A
… +6 more, Cipollone A, Simeone PG, Guagnano MT, Serra C, Santilli F, Cipollone F
Diabetes Res Clin Pract
· 2026 Jun · PMID 42009258
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AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual incretin agonist tirzepatide have demonstrated cardiometabolic benefits in cardiovascular outcome trials, but their effects on limb outcomes in peri...AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual incretin agonist tirzepatide have demonstrated cardiometabolic benefits in cardiovascular outcome trials, but their effects on limb outcomes in peripheral artery disease (PAD) remain unclear. This study evaluated whether GLP-1-based therapies reduce the risk of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality in real-world PAD populations. METHODS: A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD. RESULTS: Six studies including over 240,000 patients were analyzed. GLP-1-based therapies were associated with a significant reduction in MALE (HR 0.59, 95% CI 0.39-0.90), although heterogeneity was substantial. A significant reduction in MACE was also observed (HR 0.67, 95% CI 0.53-0.85), with greater consistency in diabetic populations. Stroke was significantly reduced (HR 0.75, 95% CI 0.63-0.89), demonstrating consistent effects across studies. Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude. CONCLUSION: In real-world PAD populations, GLP-1-based therapies are associated with meaningful reductions in both limb and cardiovascular outcomes. These findings support a vascular protective profile, particularly for stroke and MACE in more homogeneous populations such as patients with diabetes.
Yen FS, Wei JC, Hung YM
… +3 more, Liu JS, Hwu CM, Hsu CC
Diabetes Res Clin Pract
· 2026 Jun · PMID 42002149
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OBJECTIVE: To compare the risk of incident chronic kidney disease (CKD), cardiovascular events, and mortality between users of sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-users in patients with type 2 diabe...OBJECTIVE: To compare the risk of incident chronic kidney disease (CKD), cardiovascular events, and mortality between users of sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-users in patients with type 2 diabetes (T2D) without preexisting CKD. METHODS: By Taiwan's National Health Insurance Research Database (2016-2021), 1:1 propensity score matching, 11,617 pairs of SGLT2 inhibitor users and non-users with T2D and no baseline CKD were analyzed. Cox models estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for clinical outcomes. RESULTS: SGLT2 inhibitor use was associated with lower risks of incident CKD (aHR 0.86, 95% CI 0.83-0.89), macroalbuminuria (aHR 0.85, 95% CI 0.82-0.89), acute kidney injury (aHR 0.71, 95% CI 0.59-0.86), and dialysis (aHR 0.46, 95% CI 0.20-1.06). Cardiovascular benefits included reduced risks of major adverse cardiovascular events (aHR 0.84, 95% CI 0.76-0.92), hospitalization for heart failure (aHR 0.85, 95% CI 0.76-0.96), and myocardial infarction (aHR 0.68, 95% CI 0.52-0.89). All-cause mortality was also lower among SGLT2 inhibitor users (aHR 0.73, 95% CI 0.64-0.82). CONCLUSIONS: In patients with T2D without preexisting CKD, SGLT2 inhibitor use was associated with reduced risks of kidney disease, cardiovascular events, and mortality.
López-Plaza B, Larrad-Sainz A, Valerio J
… +12 more, O'Connor RM, Valle LD, Ramos-Levi AM, Barabash A, Marcuello C, Jiménez-Varas I, Runkle de la Vega I, Diaz Á, Miguel P, Rubio-Herrera MA, Matía-Martín P, Calle-Pascual AL
Diabetes Res Clin Pract
· 2026 Jun · PMID 42000050
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AIMS: To evaluate the long‒term effect of a Mediterranean-based nutritional (MedDiet) intervention during pregnancy on the prevalence of metabolic syndrome (MetS) six years postpartum, and to determine the predictive val...AIMS: To evaluate the long‒term effect of a Mediterranean-based nutritional (MedDiet) intervention during pregnancy on the prevalence of metabolic syndrome (MetS) six years postpartum, and to determine the predictive value of postpartum lifestyle behaviours for MetS prevention. METHODS: A prospective follow‒up study included 1,715 women randomised during pregnancy to an intervention or control group. Anthropometric, metabolic, and lifestyle parameters were assessed six years postpartum. Multivariate models were used to identify independent predictors of MetS. RESULTS: The intervention group showed a significantly lower prevalence of MetS (7.3 vs. 10.4 %, p = 0.034) and improved metabolic parameters. Elevated pre-pregnancy BMI (OR = 7.912 [5.411‒11.57]) and Gestational Diabetes Mellitus (GDM), diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria [(OR = 2.958 [2.056‒4.256]), were the strongest MetS modifiable risk factors. ROC analysis identified that, six years postpartum, a healthy lifestyle‒MedDiet (≥7.5 points) and physical activity (≥307.5 MET·min/week)‒reduced MetS risk by up to 62 %, after adjusting for confounders. CONCLUSIONS: GDM diagnosed using IADPSG criteria identifies women at increased long-term risk of MetS confirming its cardiovascular relevance. Early MedDiet intervention (8-12 GW) during pregnancy provides sustained metabolic benefits while pre-pregnancy BMI and GDM emerge as key modifiable determinants. Lifestyle cut-off points relevant to postpartum MetS prevention were identified.
Yang XH, Liu Y, Du JX
… +4 more, Lu YJ, Jin HM, Ye ZB, Fu CS
Diabetes Res Clin Pract
· 2026 Jun · PMID 42000049
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AIMS: Microalbuminuria, common in diabetes, lacks clarity as a predictor of diabetes onset. This study examines its association with incident type 2 diabetes (T2DM) and clinical implications. METHODS: This prospective co...AIMS: Microalbuminuria, common in diabetes, lacks clarity as a predictor of diabetes onset. This study examines its association with incident type 2 diabetes (T2DM) and clinical implications. METHODS: This prospective cohort analysis utilized data from 411,389 UK Biobank participants with baseline urine albumin-to-creatinine ratio (UACR) measurements. Cox proportional hazards regression models, supplemented by restricted cubic spline analyses, were implemented to longitudinally evaluate the association between UACR levels and incident T2DM risk. RESULTS: Over an average follow-up duration of 13.8 years (range: 13.1-14.6 years), 15,942 new cases of diabetes were identified. After adjusting for potential confounders, the hazard ratios for incident T2DM were 1.31 (95% CI: 1.17-1.45) for UACR between 3-30 mg/mmol and 2.20 (95% CI: 1.58-3.06) for UACR > 30 mg/mmol, when compared to a reference UACR of <3 mg/mmol. These results remained stable across multiple sensitivity analyses, including those addressing potential confounding factors such as body mass index, insulin resistance, uric acid levels, and estimated glomerular filtration rate using the creatinine-cystatin C equation (eGFRcr-cys). CONCLUSION: This large-scale cohort study demonstrates that microalbuminuria serves as a clinical predictor of elevated risk for incident T2DM in adults. Routine UACR screening in high-risk populations may enhance early detection and intervention.
Xiang S, Nie H, Wei Z
… +4 more, Li Y, Wang C, Che X, Du Y
Diabetes Res Clin Pract
· 2026 Jun · PMID 42000048
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BACKGROUND: The systemic influence of cardiovascular-kidney-metabolic (CKM) syndrome on gastrointestinal (GI) pathologies remains largely unexplored. We evaluated the impact of CKM stages on incident GI diseases and unde...BACKGROUND: The systemic influence of cardiovascular-kidney-metabolic (CKM) syndrome on gastrointestinal (GI) pathologies remains largely unexplored. We evaluated the impact of CKM stages on incident GI diseases and underlying proteomic mechanisms. METHODS: We analyzed 354,444 UK Biobank participants (CKM stages 0-4) free of baseline GI diseases. Cox proportional hazards models evaluated incident functional, inflammatory, and malignant GI diseases. High-throughput plasma proteomics (N = 38,031) and mediation modeling explored intermediate pathways. RESULTS: Over a median follow-up of 13.2 years, 81,168 GI cases occurred. Advanced CKM stages robustly increased overall GI risk (Stage 4 vs. 0 adjusted HR, 1.91; 95% CI, 1.84-2.00), consistent across sensitivity analyses. CKM stages 1-4 yielded a 27.1% population attributable fraction. Associations were stronger in females and individuals < 60 years, except for higher male susceptibility to colorectal cancer. Mediation modeling identified distinct plasma proteins linking CKM to these risks: immune-inflammatory networks underpinned functional and inflammatory diseases, whereas GI cancers were enriched in pro-proliferative pathways. Crucially, HGF, GDF15, and PLAUR emerged as core shared targets. CONCLUSIONS: Advanced CKM stages significantly elevate the risk of diverse GI diseases. Specific circulating proteomic signatures underlie these systemic associations. Integrating cardiometabolic profiling into GI risk stratification holds early preventive potential, requiring external validation before clinical implementation.
Hofer G, Goode S, Renström F
… +2 more, Brändle M, Cavelti-Weder C
Diabetes Res Clin Pract
· 2026 Jun · PMID 41997462
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BACKGROUND: Diabetes mellitus leads to microvascular and macrovascular complications that significantly impact quality of life. Previous cross-sectional studies may overestimate complication impacts due to methodological...BACKGROUND: Diabetes mellitus leads to microvascular and macrovascular complications that significantly impact quality of life. Previous cross-sectional studies may overestimate complication impacts due to methodological limitations. We performed a longitudinal study to assess within-patient associations between diabetes complication severity and quality of life in type 1 and 2 diabetes, providing contemporary utility estimates for cost-effectiveness analyses. METHODS: This longitudinal cohort study used Swiss diabetes registry data (2015-2022). Patients with type 1 and 2 diabetes completing ≥2 annual EQ-5D-3L questionnaires were included. We used the adapted Diabetes Complications Severity Index (aDCSI) to quantify complication severity. Associations were examined using mixed-effects regression models, adjusted for patient characteristics and survey time. RESULTS: Among 896 participants (422 type 1, 474 type 2), 83% had ≥1 complication at baseline. Type 1 patients reported better quality of life than type 2 (EQ-5D: 0.96 vs 0.88; VAS: 82.1 vs 75.5). Higher aDCSI scores were associated with reduced quality of life in both diabetes types. Women and insulin-treated patients reported lower scores. Only 4.9% developed complications. No quality of life decrement over time was observed. CONCLUSION: Diabetes complications reduce quality of life, with myocardial infarction (-0.05 EQ-5D utility) in type 2 and renal failure (-19 VAS points) in type 1, with decrements smaller than previous estimates.
Zhao T, Yu J, Deng R
… +3 more, Ding L, Li X, Mi J
Diabetes Res Clin Pract
· 2026 Jun · PMID 41985563
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BACKGROUND: This research sought to systematically estimate the accuracy of deep learning (DL) in diagnosing diabetic foot ulcers (DFUs), thereby providing novel insights for the development and updating of artificial in...BACKGROUND: This research sought to systematically estimate the accuracy of deep learning (DL) in diagnosing diabetic foot ulcers (DFUs), thereby providing novel insights for the development and updating of artificial intelligence (AI)-assisted tools. METHODS: This study searched PubMed, Cochrane, Embase, and Web of Science up to October 2025 for original studies that used image-based DL to detect DFUs. The risk of bias of the included studies was estimated utilizing QUADAS-AI. In the meta-analysis, we constructed diagnostic 2 × 2 tables and applied a bivariate mixed-effects model. RESULTS: In total, 55 studies were included. Of these, 32 were included in the meta-analysis, involving 87 diagnostic 2 × 2 tables for validating DL models. The pooled results exhibited that for the overall validation sets, the sensitivity and specificity were 0.96 (95% CI: 0.94-0.98) and 0.97 (95% CI: 0.94-0.98), respectively. In multicenter datasets, the sensitivity, specificity, 0.87 (95% CI: 0.68-0.96), 0.92 (95% CI: 0.82-0.97). CONCLUSIONS: This research discloses that image-based DL for detecting DFUs might be a promising approach. Future studies should further ascertain the generalizability of models derived from public databases to individual-level data across diverse geographic regions, thereby providing evidence for the evaluation and development of AI-assisted tools.
Maldonado AI, Salas J, Schnurr PP
… +6 more, Cohen BE, Jaffe AS, Freedland KE, Lustman PJ, Friedman M, Scherrer JF
Diabetes Res Clin Pract
· 2026 Jun · PMID 41985562
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AIMS: Posttraumatic stress disorder (PTSD) is associated with type 2 diabetes (T2D). However, no studies have determined if risk for adverse T2D outcomes vary among different PTSD comorbidity patterns. METHODS: We identi...AIMS: Posttraumatic stress disorder (PTSD) is associated with type 2 diabetes (T2D). However, no studies have determined if risk for adverse T2D outcomes vary among different PTSD comorbidity patterns. METHODS: We identified 152,171 Veterans Health Administration (VHA) patients with de-identified medical records who had comorbid PTSD and T2D. All had adequate HbA1c control, not on insulin, and were free of microvascular and macrovascular complications at index. Latent class analyses (LCA) identified 3 comorbidity profiles characterized as depression + anxiety; high comorbidity; and low comorbidity. We then estimated the link between comorbidity classes and risk for adverse T2D outcomes and all-cause mortality. RESULTS: Most (64.4%) of the sample was ≥ 60 years of age, male (90.9%), and White race (69.1%). High comorbidity vs. low comorbidity and depression + anxiety vs. low comorbidity were associated with all-cause mortality (HR = 1.39; 95%CI:1.28-1.50 and HR = 1.18;95%CI:1.14-1.23, respectively). The depression + anxiety vs. the low comorbidity class, had slightly worse glycemic control (HR = 1.04; 95%CI:1.02-1.06) and microvascular complications (HR = 1.04; 95%CI:1.02-1.06). CONCLUSIONS: More psychiatric comorbidity in patients with PTSD is associated with worse glycemic control, increased risk for T2D micro- and macro- complications, and mortality. Research is needed to determine if treatment and improvement in patients with comorbid psychiatric disorders leads to improved T2D outcomes.
Dankoob V, Shahinfar H, Ostevari A
… +5 more, Norouziasl R, Mohieddin N, Esmaeili F, Rafiei F, Shab-Bidar S
Diabetes Res Clin Pract
· 2026 Jun · PMID 41974358
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This study aimed to assess, compare, and rank the effects of different behavioral interventions on key cardiovascular risk factors in adults with type 2 diabetes. We searched PubMed, Scopus, and Web of Science up to Marc...This study aimed to assess, compare, and rank the effects of different behavioral interventions on key cardiovascular risk factors in adults with type 2 diabetes. We searched PubMed, Scopus, and Web of Science up to March 2025. A random-effects network meta-analysis with a Frequentist framework was conducted to estimate mean differences (MDs) and 95% confidence intervals (CIs). The certainty of evidence was rated using the GRADE approach. Standard behavioral therapy (SBT) improved short-term glycemic control, reducing HbA1c by 0.24% (95% CI: -0.41, -0.06) at 0-3 months with moderate-certainty evidence. Multicomponent interventions, particularly those combining cognitive behavioral therapy (CBT), SBT, and motivational interviewing (MI), showed the largest and most sustained effects, achieving a 1.84% HbA1c reduction (95% CI: -2.04, -1.63) at 12-36 months compared with SBT alone. SBT also reduced systolic blood pressure and increased HDL cholesterol. Ranking analyses indicated that SBT + mindfulness-based interventions, ACT/DBT-based approaches, and CBT + SBT + MI were most effective for HbA1c reduction. For fasting blood glucose, CBT combined with SBT or MI showed the highest effectiveness, while SBT plus control ranked well at 6-12 months. Overall, multicomponent behavioral strategies appear most effective for sustained HbA1c improvement, although stronger evidence is needed for fasting glucose and adiposity outcomes.
Jagannathan R, Oguntade AS, Deepa M
… +12 more, Kondal D, Anjana RM, Patel SA, Carrillo-Larco RM, Mohan S, Chang HH, Ali MK, Quyyumi AA, Prabhakaran D, Mohan V, Narayan KMV, Tandon N
Diabetes Res Clin Pract
· 2026 Jun · PMID 41966281
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OBJECTIVE: We examined associations between age at type 2 diabetes (T2D) diagnosis and long-term mortalityand lifetime health loss. RESEARCH DESIGN AND METHODS: We analyzed data from the population-based CARRS cohort. T2...OBJECTIVE: We examined associations between age at type 2 diabetes (T2D) diagnosis and long-term mortalityand lifetime health loss. RESEARCH DESIGN AND METHODS: We analyzed data from the population-based CARRS cohort. T2D was defined by self-report, glucose-lowering medication use, or glycemic thresholds and categorized by age at diagnosis (20-29, 30-39, 40-59, or ≥60 years). Hazard ratios (HRs) were estimated using time-dependent Cox models with participants without T2D as reference group. Model-based projections estimated years of life lost (YLL), years lived with disability (YLD), disability-adjusted life years (DALYs), and excess life-years lost (LYL). RESULTS: Among 21,574 participants (mean age 43.3 years), 6,251 had diabetes. Over a median follow-up of 8.7 years, 2,163 deaths occurred. Younger age at T2D diagnosis was associated with higher risks of mortality and cardiovascular events. Adjusted HRs for all-cause mortality were 2.98 (95% CI 1.60-5.54) for T2D diagnosis at 20-29 years, 2.28 (1.74-2.98) at 30-39 years, 1.73 (1.47-2.04) at 40-59 years, and 1.61 (1.30-1.99) at ≥60 years. Projected lifetime DALYs were greatest with younger diagnosis, ranging from 24.5 years for diagnosis at 20-29 years to 5.5 years at > 60 years, with similar gradients for excess LYL.This pattern was also observed for CVD eventsacross age groups. CONCLUSIONS: T2D diagnosed at a younger age was associated with higher mortalityand greater LYL in South Asians.
Diabetes Res Clin Pract
· 2026 Jun · PMID 41966280
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BACKGROUND: Estimated glucose disposal rate (eGDR) and frailty index (FI) captures insulin resistance and multisystem decline, respectively. However, the combined prognostic value of eGDR and FI for cardiovascular diseas...BACKGROUND: Estimated glucose disposal rate (eGDR) and frailty index (FI) captures insulin resistance and multisystem decline, respectively. However, the combined prognostic value of eGDR and FI for cardiovascular diseases (CVD) and mortality remains underexplored. METHODS: This prospective cohort study included 6,684 participants from the CHARLS. The composite index eGDRFI was calculated as FI/eGDR. The study endpoints were incident CVD, stroke, heart disease, and all-cause mortality. RESULTS: After adjustment, each 1-unit increase in eGDRFI was significantly associated with higher risks of CVD (HR = 1.098, 95% CI 1.061-1.136) and all-cause mortality (HR = 1.080, 95% CI 1.048-1.113) (both P < 0.001). Compared to the lowest quartile (Q1), participants in the highest eGDRFI quartile (Q4) had markedly increased risks of CVD (HR = 1.833, 95% CI 1.494-2.249) and mortality (HR = 1.511, 95% CI 1.212-1.884) (both P < 0.001). ROC curve analysis demonstrated that eGDRFI achieved higher discriminative ability for predicting incident CVD (AUC = 0.600) compared to eGDR (AUC = 0.590) and FI (AUC = 0.563), as well as for predicting all-cause mortality (eGDRFI AUC = 0.606 vs. eGDR 0.547 and FI 0.601). CONCLUSION: The combined eGDRFI is a robust predictor of cardiovascular events and mortality in middle-aged and older adults, and may serve as a practical tool for risk stratification.
Diabetes Res Clin Pract
· 2026 Jun · PMID 41962634
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Epigenetic age acceleration (EAA), a discrepancy between biological and chronological age based on DNA methylation patterns, has emerged as a critical marker for aging and metabolic health. Individuals with diabetes, par...Epigenetic age acceleration (EAA), a discrepancy between biological and chronological age based on DNA methylation patterns, has emerged as a critical marker for aging and metabolic health. Individuals with diabetes, particularly type 2 diabetes (T2D), exhibit notable EAA, linking the disease to accelerated biological ageing. This review explores the mechanisms underlying EAA in diabetes, including hyperglycaemia-induced oxidative stress, inflammation, and dysregulated epigenetic pathways. Additionally, we discuss the clinical implications of EAA, emphasizing its potential as a biomarker for diabetes-related complications and a predictor of cardiovascular disease, nephropathy, and premature mortality. Emerging therapeutic strategies targeting epigenetic mechanisms, such as dietary interventions, pharmacological agents, and lifestyle modifications, are also reviewed. Understanding the interplay between EAA and diabetes opens avenues for personalized medicine and innovative treatments aimed at mitigating the accelerated aging phenotype associated with diabetes.
Delgado N, Chaytor NS, Beeri MS
… +17 more, Hawks ZW, Jung L, Cleveland M, Bulger J, Grinspoon E, Janess K, Zuniga-Kennedy M, Sliwinski MJ, Chhatwal JP, Kivisäkk P, Kudva YC, Rizvi S, Rickels MR, Pratley R, Weinstock RS, Germine LT, Fonseca LM
Diabetes Res Clin Pract
· 2026 Jun · PMID 41962633
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AIMS: Type 1 diabetes (T1D) is associated with an increased risk of Alzheimer's disease and related dementias (AD/ADRD), although mechanisms remain unclear. This study examined the relationships between blood-based bioma...AIMS: Type 1 diabetes (T1D) is associated with an increased risk of Alzheimer's disease and related dementias (AD/ADRD), although mechanisms remain unclear. This study examined the relationships between blood-based biomarkers of ADRD, diabetes-related factors, and glycemia in adults with T1D. METHODS: This study analyzed 114 adults from the Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) Study with available plasma samples. Regression models assessed relationships between biomarkers (Aβ42/Aβ40 ratio, GFAP, NfL, pTau181, pTau217), diabetes characteristics, and continuous glucose monitoring metrics (up to 20 days), adjusting for demographics and kidney disease. False discovery rate (FDR) correction was applied. RESULTS: Lower Aβ42/Aβ40 ratios were associated with older age of T1D diagnosis and higher NfL concentrations with higher mean glucose, lower glucose time in range, more time spent with glucose above 180 and 250 mg/dL, higher HbA1c, neuropathy, and diabetic ketoacidosis. These remained significant after additional adjustment for kidney disease, although residual confounding by renal function cannot be excluded. CONCLUSIONS: Higher NfL was linked with multiple measures of hyperglycemia and other diabetes-related complications, consistent with neuronal injury rather than suggesting an ADRD-specific process. Longitudinal studies are needed to clarify the mechanisms between NfL and glycemia in T1D.
Seget S, Rusak E, Pelicand J
… +10 more, Fry M, Sheanon N, Schierloh U, Xatzipsalti M, Malinici E, Tinti D, Neylon O, Bazdarska Y, Cobry E, Hauser E
Diabetes Res Clin Pract
· 2026 Jun · PMID 41962632
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AIMS: Automated insulin delivery (AID) systems are increasingly used in type 1 diabetes (T1D) management, yet large-scale real-world evidence in pediatric populations remains limited. This study assessed the impact of AI...AIMS: Automated insulin delivery (AID) systems are increasingly used in type 1 diabetes (T1D) management, yet large-scale real-world evidence in pediatric populations remains limited. This study assessed the impact of AID therapy on glycemic outcomes in children and adolescents with T1D using data from the international SWEET registry. METHODS: We performed an observational comparative study using two treatment periods (12 months before and after AID initiation). Data were obtained from the SWEET database, with 53 centers across 29 countries contributing eligible cases. Participants were children and adolescents (≤18 years) with T1D who initiated AID therapy between 2014 and 2022. Primary endpoints included HbA1c, mean sensor glucose, and percentages of time spent in predefined glycemic ranges. RESULTS: A total of 2,170 participants were included. AID therapy was associated with significant improvements in glycemic control. Time in the target range (70-180 mg/dL) and tight target range (70-140 mg/dL) increased, while mean sensor glucose and glucose variability decreased. Time below range (<70 mg/dL) was reduced. HbA1c improved without a significant change in total daily insulin dose. CONCLUSIONS: In this large multinational real-world cohort, AID therapy significantly improved glycemic outcomes and reduced hypoglycemia in children and adolescents with T1D. These findings support the effectiveness of AID systems across diverse clinical settings and underscore their value in pediatric diabetes care.
Tang M, Feng J, Ni Y
… +3 more, Zhang W, Zhou M, Zhao C
Diabetes Res Clin Pract
· 2026 Jun · PMID 41962631
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Diabetic foot ulcers (DFUs) are devastating complications of diabetes, defined by impaired healing, high amputation rates, and substantial mortality, with pathogenesis rooted in interconnected metabolic, immune, and vasc...Diabetic foot ulcers (DFUs) are devastating complications of diabetes, defined by impaired healing, high amputation rates, and substantial mortality, with pathogenesis rooted in interconnected metabolic, immune, and vascular dysregulation. Serum metabolomic profiling identifies elevated branched-chain amino acid (BCAA) levels in DFU patients, yet the metabolic mechanisms linking BCAA dysregulation to DFU remain unexplored. This review systematically presents a causal framework: impairment of the BCAA metabolic process (downregulation of BCKDH in skeletal muscle/fat tissue), dysbiosis of the intestinal microbiota leading to systemic accumulation of BCAA, and subsequent activation of the mTORC1/NF-κB signaling cascade. This triggers insulin resistance, mitochondrial dysfunction, and oxidative stress, causing macrophages to polarize to the pro-inflammatory M1 phenotype, disrupting the functions of NK cells and neutrophils, and inhibiting angiogenesis mediated by HIF-1α/VEGF forming a self-perpetuating metabolic-immune-vascular vicious cycle, thereby delaying the wound healing process. This review aims to provide a metabolism-centered framework for understanding the pathogenesis of DFU and for informing future diagnostic and therapeutic research.
Diabetes Res Clin Pract
· 2026 Jun · PMID 41956292
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BACKGROUND: Gray matter (GM) structural alterations and its correlation with cognitive decline in type 1 diabetes mellitus (T1DM) remain unclear. METHODS: We investigated GM structural alterations associated with cogniti...BACKGROUND: Gray matter (GM) structural alterations and its correlation with cognitive decline in type 1 diabetes mellitus (T1DM) remain unclear. METHODS: We investigated GM structural alterations associated with cognitive decline in T1DM, utilizing a Voxel-based Morphometry (VBM) method to analyze structural magnetic resonance imaging (MRI) data from T1DM patients and mice. In clinical study, we recruited 73 adults, including 31 with T1DM, and 42 healthy controls (HCs). The GM volumes of different brain regions were quantified by utilizing VBM method. Correlation and mediation analysis were conducted to explore relationships between aberrant MRI indices and clinical variables and neuropsychological scores. In animal experiment, we conducted Morris water maze test and cranial MRI examinations on normal control mice (NC, n = 12) and T1DM mice (T1DM, n = 24) to detect GM structural alterations in T1DM mice with cognitive decline. FINDINGS: In clinical research, compared to HCs, T1DM patients exhibited a significant decrease in GM volume of the right cerebellar Crus I. The GM volumes of cerebellar lobules were closely related to cognitive scores and serum lipid levels in T1DM patients. In animal experiments, compared to the NC group, the T1DM mice exhibited the GM atrophy of 23 brain regions, including cerebellum, prefrontal cortex. INTERPRETATION: The GM volumes of cerebellar lobules were associated with cognitive scores in T1DM patients, suggesting that GM structural alterations in these lobules may be involved in the neuropathological mechanisms of brain damage in T1DM. And the GM atrophy in T1DM mice confirmed those changes in T1DM patients and provided valuable information for identifying potential vulnerable brain areas associated with cognitive decline in T1DM.
Giaccari A, Borroni F, Dauriz M
… +6 more, Gioia D, Baptiste P, Bisio A, Lastoria G, Udupa K, Barbagallo M
Diabetes Res Clin Pract
· 2026 Jun · PMID 41951127
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AIMS: To evaluate glycemic control, weight management, and patient-reported outcomes (PROs) in adults with type 2 diabetes mellitus who transitioned to oral semaglutide (OS) after inadequate glycemic control on dipeptidy...AIMS: To evaluate glycemic control, weight management, and patient-reported outcomes (PROs) in adults with type 2 diabetes mellitus who transitioned to oral semaglutide (OS) after inadequate glycemic control on dipeptidyl peptidase-4 inhibitors (DPP-4i). METHODS: This 40-week, observational, prospective study included three visits: baseline (V1, OS initiation), intermediate visits (V2.X), and final visit (V3, week 40 ± 4). The primary endpoint was change in glycated haemoglobin (HbA1c) from V1 to V3. Secondary endpoints included changes in body weight (BW), PROs - assessed by the Diabetes Distress Scale (DDS) and the Dutch Eating Behaviour Questionnaire (DEBQ) - and anthropometric/clinical parameters. RESULTS: 281 patients were enrolled (mean age 67.5 ± 12.0 years; 55.9% male). In the in-study set (all patients initiating OS, regardless of discontinuation), mean HbA1c decreased by - 0.7 ± 0.05% (p < 0.0001), and mean BW decreased by - 3.6 ± 0.22 kg (p < 0.0001) from V1 to V3. Scores on the DDS domains and the DEBQ (emotional and external eating domains) decreased, indicating reduced diabetes-related distress and improved eating behaviours. Adverse events were reported by 23.1% of patients, with no hypoglycaemic episodes observed. CONCLUSIONS: OS was safe and effective in improving glycemic control, reducing BW, and alleviating diabetes-related distress and unhealthy eating behaviors in patients with type 2 diabetes mellitus switched from DPP-4i.