To investigate the prevalence and clinical characteristics of distal symmetrical polyneuropathy (DSPN) in prediabetes and associations with cardiometabolic risk factors, insulin resistance and arterial stiffness.
Methods
Consecutive adults with prediabetes attending the Outpatient Lipid and Obesity Clinic at the University Hospital of Ioannina, Greece were recruited. This is a cross sectional- analysis of the baseline characteristics of a prospective observational study. DSPN was diagnosed using the neuropathy symptom score (NSS), the neuropathy disability score (NDS) and the vibration perception threshold (VTP). Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV).
Results
We studied 160 consecutive adults with prediabetes, of whom 27 (16.9%) were diagnosed with DSPN. In multivariate analysis, waist circumference (OR: 1.092, 95% CI: 1.037–1.148, p < 0.001) and HOMA-IR (OR: 1.247, 95% CI: 1.095–1.425, p = 0.004) were independently associated with prevalent DSPN. Additionally, sensitivity analysis showed that current/previous smoking vs never-smoking (OR: 1.347, 95% CI: 1.116–1.891, p = 0.042) and height (OR: 1.083, 95% CI: 1.004–1.168, p = 0.039) were independently linked with prevalent DSPN. Subjects with DSPN had significantly higher median PWV (8.8 vs 8.0 m/s, p = 0.031) and prevalence of abnormal PWV (≥10 m/s) (29.6% vs 11.3%, p = 0.029) compared with no DSPN. PWV was independently associated with VPT (beta: 1.010, 95% CI:0.123–1.897, p = 0.026).
Conclusions
The prevalence of DSPN in prediabetes is not negligible in our study. DSPN is independently associated with central obesity and insulin resistance.
目的：探讨糖尿病前期远端对称性多神经病变（DSPN）的患病率、临床特征及其与心脏代谢危险因素、胰岛素抵抗和动脉僵硬的关系。方法：在希腊约阿尼纳大学医院脂质和肥胖门诊连续招募患有前驱糖尿病的成年人。这是一项前瞻性观察性研究的基线特征的横断面分析。采用神经病变症状评分（NSS）、神经病变失能评分（NDS）和振动感知阈值（VTP）诊断DSPN。用颈-股脉波速度（PWV）评估动脉僵硬度。结果：我们研究了160名连续患有前驱糖尿病的成年人，其中27人（16.9%）被诊断为DSPN。在多变量分析中，腰围（OR: 1.092, 95% CI: 1.037-1.148, p ）结论：在我们的研究中，DSPN在前驱糖尿病中的患病率不容忽视。DSPN与中心性肥胖和胰岛素抵抗独立相关。
{"title":"Distal symmetrical polyneuropathy in prediabetes is associated with abdominal obesity and insulin resistance","authors":"Georgia Anastasiou , Nikolaos Papanas , Fotios Barkas , Nicholas Tentolouris , Georgios Liamis , Lampros K. Michalis , Aris Bechlioulis , Rigas Kalaitzidis , Evangelos Liberopoulos","doi":"10.1016/j.diabres.2026.113140","DOIUrl":"10.1016/j.diabres.2026.113140","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the prevalence and clinical characteristics of distal symmetrical polyneuropathy (DSPN) in prediabetes and associations with cardiometabolic risk factors, insulin resistance and arterial stiffness.</div></div><div><h3>Methods</h3><div>Consecutive adults with prediabetes attending the Outpatient Lipid and Obesity Clinic at the University Hospital of Ioannina, Greece were recruited. This is a cross sectional- analysis of the baseline characteristics of a prospective observational study. DSPN was diagnosed using the neuropathy symptom score (NSS), the neuropathy disability score (NDS) and the vibration perception threshold (VTP). Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV).</div></div><div><h3>Results</h3><div>We studied 160 consecutive adults with prediabetes, of whom 27 (16.9%) were diagnosed with DSPN. In multivariate analysis, waist circumference (OR: 1.092, 95% CI: 1.037–1.148, p < 0.001) and HOMA-IR (OR: 1.247, 95% CI: 1.095–1.425, p = 0.004) were independently associated with prevalent DSPN. Additionally, sensitivity analysis showed that current/previous smoking vs never-smoking (OR: 1.347, 95% CI: 1.116–1.891, p = 0.042) and height (OR: 1.083, 95% CI: 1.004–1.168, p = 0.039) were independently linked with prevalent DSPN. Subjects with DSPN had significantly higher median PWV (8.8 vs 8.0 m/s, p = 0.031) and prevalence of abnormal PWV (≥10 m/s) (29.6% vs 11.3%, p = 0.029) compared with no DSPN. PWV was independently associated with VPT (beta: 1.010, 95% CI:0.123–1.897, p = 0.026).</div></div><div><h3>Conclusions</h3><div>The prevalence of DSPN in prediabetes is not negligible in our study. DSPN is independently associated with central obesity and insulin resistance.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113140"},"PeriodicalIF":7.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1016/j.diabres.2026.113136
Kate M. Seaton , Hanna C. Jones , Melissa H. Lee , Gary Kilov , Alicia J. Jenkins , Landy M. Wu , Cecilia Pham , Frank Gao , Elif I. Ekinci , Pamela Taylor , Stephen Stranks , Megan Herson , Jennifer Wong , Barbora Paldus , Dev Kevat , Adamandia Kriketos , Spiros Fourlanos , John Wentworth , Katherine Wu , Harsan Kanagaretnam , David N. O’Neal
Aim
To compare real-world glycaemic and clinical outcomes in adults with Type 1 Diabetes (T1DM) using Automated Insulin Delivery (AID) vs. those using manual insulin delivery.
Methods
Demographic and diabetes-related glycaemic and clinical data were prospectively collected via a survey from consecutive participants with T1DM attending TIDM clinics in Australia during 2024–25.
Results
Of 406 participants surveyed (233 females [57.4%], age 45.6 ± 16.5 years). AID was used by 141 participants (34.8%), with 50.2% of non-users expressing interest in AID use. AID use vs. non-use was associated with lower HbA1c (7.2 ± 1.0% [63 ± 19 mmol/mol] vs 7.9 ± 1.6% [63 ± 18 mmol/mol], p < 0.001), Glucose Management Indicator (GMI) (7.2 ± 0.8% [55 ± 8 mmol/mol vs 8.0 ± 1.4% [63 ± 15 mmol/mol], p < 0.001), and higher Time In Range (TIR) (69.21 ± 14.79% vs 50.53 ± 21.8%, p < 0.001), with fewer severe hypoglycaemia episodes (n = 3 [2.1%] vs n = 31 [11.7%], p < 0.001). These associations were observed irrespective of Socio-Economic Indexes for Areas (SEIFA) group.
Conclusion
AID use was associated with better glycaemic and clinical outcomes irrespective of socio-economic status. AID use tended to be more prevalent among the socio-economically advantaged. We strongly advocate for equitable AID access based on clinical need rather than financial means.
{"title":"Survey of glucose levels in adults with T1DM attending clinic using automated insulin delivery (AID) devices compared with manual insulin delivery","authors":"Kate M. Seaton , Hanna C. Jones , Melissa H. Lee , Gary Kilov , Alicia J. Jenkins , Landy M. Wu , Cecilia Pham , Frank Gao , Elif I. Ekinci , Pamela Taylor , Stephen Stranks , Megan Herson , Jennifer Wong , Barbora Paldus , Dev Kevat , Adamandia Kriketos , Spiros Fourlanos , John Wentworth , Katherine Wu , Harsan Kanagaretnam , David N. O’Neal","doi":"10.1016/j.diabres.2026.113136","DOIUrl":"10.1016/j.diabres.2026.113136","url":null,"abstract":"<div><h3>Aim</h3><div>To compare real-world glycaemic and clinical outcomes in adults with Type 1 Diabetes (T1DM) using Automated Insulin Delivery (AID) vs. those using manual insulin delivery.</div></div><div><h3>Methods</h3><div>Demographic and diabetes-related glycaemic and clinical data were prospectively collected via a survey from consecutive participants with T1DM attending TIDM clinics in Australia during 2024–25.</div></div><div><h3>Results</h3><div>Of 406 participants surveyed (233 females [57.4%], age 45.6 ± 16.5 years). AID was used by 141 participants (34.8%), with 50.2% of non-users expressing interest in AID use. AID use vs. non-use was associated with lower HbA1c (7.2 ± 1.0% [63 ± 19 mmol/mol] vs 7.9 ± 1.6% [63 ± 18 mmol/mol], <em>p</em> < 0.001), Glucose Management Indicator (GMI) (7.2 ± 0.8% [55 ± 8 mmol/mol vs 8.0 ± 1.4% [63 ± 15 mmol/mol], <em>p</em> < 0.001), and higher Time In Range (TIR) (69.21 ± 14.79% vs 50.53 ± 21.8%, <em>p</em> < 0.001), with fewer severe hypoglycaemia episodes (n = 3 [2.1%] vs n = 31 [11.7%], <em>p</em> < 0.001). These associations were observed irrespective of Socio-Economic Indexes for Areas (SEIFA) group.</div></div><div><h3>Conclusion</h3><div>AID use was associated with better glycaemic and clinical outcomes irrespective of socio-economic status. AID use tended to be more prevalent among the socio-economically advantaged. We strongly advocate for equitable AID access based on clinical need rather than financial means.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113136"},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Objective: </strong>This study characterizes the hemodynamic abnormalities of the microcirculation in the feet of patients with diabetic foot (DF) based on multidimensional features, including time-domain and frequency-domain metrics, rhythmicity, and symmetry. It further elucidates the relationship between these abnormalities and plantar pressure hotspots, specifically the forefoot first metatarsal head (MT1) and fifth metatarsal head (MT5), and constructs a cross-sectional discriminative model.</p><p><strong>Methods: </strong>A total of 286 consecutive participants were included in the study (non-DF: 157, DF: 129). Microcirculation signals from MT1 and MT5 were collected, with features extracted across various domains: time (mean, standard deviation, range, kurtosis), frequency domain (relative power endothelial, neurogenic, myogenic, respiratory, and cardiac bands), rhythmicity (number of peaks, peak intervals, and their dispersion), and symmetry (absolute value of the mean difference between left and right, left-right correlation coefficient). Inter-group comparisons were conducted using the Mann-Whitney U test, and effect sizes were calculated with the Hodges-Lehmann median difference (Δ) and Cliff's δ. Correlations were assessed using Spearman's method with Benjamini-Hochberg false discovery rate (BH-FDR) correction. Variables selected by LASSO were entered into a multivariable logistic regression model. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), and the optimal classification threshold was determined using the Youden index.</p><p><strong>Results: </strong>Mean perfusion at MT1 and MT5 was significantly lower in the DF group (both p < 0.001), representing the largest between-group differences among the assessed features. Variability metrics differed by measurement site. Notably, the relative power in the neurogenic and myogenic bands at MT1 was significantly decreased, suggesting a weakening of low-frequency autonomic regulation. Furthermore, MT1 exhibited fewer peaks, prolonged inter-peak intervals, and increased dispersion, indicating slower and less stable rhythmicity. Left-right correlation coefficients at bothsites were decreased (p < 0.001), whereas the absolute left-right mean differences did not increase, suggesting reduced synchrony rather than increased amplitude asymmetry. Spearman correlation and multifactor models consistently aligned in direction. Regarding the discriminative models, the area under the curve (AUC) for the MT1 model was 0.845, for the MT5 model was 0.822, and for the combined model (MT1 + MT5) was 0.906, which outperformed the single-site models.</p><p><strong>Conclusion: </strong>Patients with DF demonstrate a composite pattern of microcirculatory dysfunction characterized by insufficient perfusion, attenuated autonomic regulation, altered rhythmicity, and impaired bilateral coordination. Multidimensional plantar microcirculatory featu
{"title":"Multidimensional feature-based assessment of microcirculatory hemodynamic dysfunction in patients with Wagner Grade 0 diabetic foot.","authors":"Yanan Zhao, Jing Zhang, Yangxi Li, Ziwei Hu, Qi Qi, Shengmei Zhao, Lingyu Zhang, Liwei Jing","doi":"10.1016/j.diabres.2026.113138","DOIUrl":"10.1016/j.diabres.2026.113138","url":null,"abstract":"<p><strong>Objective: </strong>This study characterizes the hemodynamic abnormalities of the microcirculation in the feet of patients with diabetic foot (DF) based on multidimensional features, including time-domain and frequency-domain metrics, rhythmicity, and symmetry. It further elucidates the relationship between these abnormalities and plantar pressure hotspots, specifically the forefoot first metatarsal head (MT1) and fifth metatarsal head (MT5), and constructs a cross-sectional discriminative model.</p><p><strong>Methods: </strong>A total of 286 consecutive participants were included in the study (non-DF: 157, DF: 129). Microcirculation signals from MT1 and MT5 were collected, with features extracted across various domains: time (mean, standard deviation, range, kurtosis), frequency domain (relative power endothelial, neurogenic, myogenic, respiratory, and cardiac bands), rhythmicity (number of peaks, peak intervals, and their dispersion), and symmetry (absolute value of the mean difference between left and right, left-right correlation coefficient). Inter-group comparisons were conducted using the Mann-Whitney U test, and effect sizes were calculated with the Hodges-Lehmann median difference (Δ) and Cliff's δ. Correlations were assessed using Spearman's method with Benjamini-Hochberg false discovery rate (BH-FDR) correction. Variables selected by LASSO were entered into a multivariable logistic regression model. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), and the optimal classification threshold was determined using the Youden index.</p><p><strong>Results: </strong>Mean perfusion at MT1 and MT5 was significantly lower in the DF group (both p < 0.001), representing the largest between-group differences among the assessed features. Variability metrics differed by measurement site. Notably, the relative power in the neurogenic and myogenic bands at MT1 was significantly decreased, suggesting a weakening of low-frequency autonomic regulation. Furthermore, MT1 exhibited fewer peaks, prolonged inter-peak intervals, and increased dispersion, indicating slower and less stable rhythmicity. Left-right correlation coefficients at bothsites were decreased (p < 0.001), whereas the absolute left-right mean differences did not increase, suggesting reduced synchrony rather than increased amplitude asymmetry. Spearman correlation and multifactor models consistently aligned in direction. Regarding the discriminative models, the area under the curve (AUC) for the MT1 model was 0.845, for the MT5 model was 0.822, and for the combined model (MT1 + MT5) was 0.906, which outperformed the single-site models.</p><p><strong>Conclusion: </strong>Patients with DF demonstrate a composite pattern of microcirculatory dysfunction characterized by insufficient perfusion, attenuated autonomic regulation, altered rhythmicity, and impaired bilateral coordination. Multidimensional plantar microcirculatory featu","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113138"},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1016/j.diabres.2026.113137
Rodney Kwok , Kartik Kishore , Tina Zafari , Digsu N. Koye , Mariam Hachem , Ian H. de Boer , Tae-Dong Jeong , Won-Ki Min , Esteban Porrini , Petter Bjornstad , Yih Chung Tham , Richard J. MacIsaac , Leonid Churilov , Elif I. Ekinci
Background
Existing methods for estimating GFR in people with diabetes have shown inaccuracies when compared to mGFR measurements. We developed and validated an artificial neural network – RenoTrue to improve estimating GFR in people with diabetes.
Methods
5,619 individuals from five international cohorts with type 1 and type 2 diabetes was split into training (70%), validation (10%) and test (20%) datasets. RenoTrue was developed to estimate GFR using age, sex, and serum creatinine. The performance was evaluated in the test dataset by estimating agreement, bias (mean difference), and accuracy (p30), and compared to CKD-EPI estimates through a multi-level mixed effect regression model.
Findings
Median mGFR was 75 ml/ min per 1.73 m2 [IQR: 49, 100] and median age was 59 years [IQR: 38, 69]. RenoTrue demonstrated high agreement (ICC: 0.87 (95% CI: 0.78, 0.93)), low bias (−0.57 (95% CI: -1.59, 0.46) ml/min per 1.73 m2) and p30 of 81% (95% CI: 79%, 83%) compared to mGFR measurements. The 2009 CKD-EPI equation had an ICC of 0.86 (95% CI: 0.77, 0.92), bias of 4.17 (95% CI: 3.14, 5.20) ml/min per 1.73 m2 and p30 of 74% (95% CI: 72%, 77%).
Conclusion
For people with diabetes, RenoTrue demonstrated better performance compared to the 2009 CKD-EPI equation in terms of estimating GFR across the full range of GFR.
{"title":"RenoTrue: A diabetes-specific machine learning model to estimate glomerular filtration rate for people with diabetes","authors":"Rodney Kwok , Kartik Kishore , Tina Zafari , Digsu N. Koye , Mariam Hachem , Ian H. de Boer , Tae-Dong Jeong , Won-Ki Min , Esteban Porrini , Petter Bjornstad , Yih Chung Tham , Richard J. MacIsaac , Leonid Churilov , Elif I. Ekinci","doi":"10.1016/j.diabres.2026.113137","DOIUrl":"10.1016/j.diabres.2026.113137","url":null,"abstract":"<div><h3>Background</h3><div>Existing methods for estimating GFR in people with diabetes have shown inaccuracies when compared to mGFR measurements. We developed and validated an artificial neural network – RenoTrue to improve estimating GFR in people with diabetes.</div></div><div><h3>Methods</h3><div>5,619 individuals from five international cohorts with type 1 and type 2 diabetes was split into training (70%), validation (10%) and test (20%) datasets. RenoTrue was developed to estimate GFR using age, sex, and serum creatinine. The performance was evaluated in the test dataset by estimating agreement, bias (mean difference), and accuracy (p30), and compared to CKD-EPI estimates through a multi-level mixed effect regression model.</div></div><div><h3>Findings</h3><div>Median mGFR was 75 ml/ min per 1.73 m<sup>2</sup> [IQR: 49, 100] and median age was 59 years [IQR: 38, 69]. RenoTrue demonstrated high agreement (ICC: 0.87 (95% CI: 0.78, 0.93)), low bias (−0.57 (95% CI: -1.59, 0.46) ml/min per 1.73 m<sup>2</sup>) and p30 of 81% (95% CI: 79%, 83%) compared to mGFR measurements. The 2009 CKD-EPI equation had an ICC of 0.86 (95% CI: 0.77, 0.92), bias of 4.17 (95% CI: 3.14, 5.20) ml/min per 1.73 m<sup>2</sup> and p30 of 74% (95% CI: 72%, 77%).</div></div><div><h3>Conclusion</h3><div>For people with diabetes, RenoTrue demonstrated better performance compared to the 2009 CKD-EPI equation in terms of estimating GFR across the full range of GFR.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113137"},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.diabres.2026.113111
Ritu Dahiya, Ajay Pal Singh, Aruna Rawat
Type 2 diabetes is increasingly recognised as a condition driven by sustained metabolic overload and chronic low-grade inflammation rather than a simple decline in insulin secretion. Findings from single-cell transcriptomics, human islet studies, and metabolic profiling show that pancreatic β-cells undergo progressive alterations in identity when exposed to glucotoxic, lipotoxic, oxidative, and inflammatory stress. In parallel, cytokines, lipid intermediates, adipose-derived factors, hepatokines, myokines, and gut microbial metabolites generate an immunometabolic environment that accelerates β-cell dedifferentiation and promotes transitions toward progenitor-like or alternative endocrine states. Originally described through lineage-tracing studies in experimental models, β-cell dedifferentiation is now recognized as a dynamic and potentially reversible process shaped by immunometabolic stress in diabetes. This review synthesizes current evidence to illustrate how metabolic and immune pathways converge on key molecular regulators of β-cell fate. It further describes how interorgan communication reinforces these disturbances and contributes to the gradual shift of β-cells along a continuum of stress adaptation, functional decline, and identity loss. A conceptual framework, referred to as the beta-cell identity clock, is presented to capture the dynamic and potentially reversible nature of these transitions. Finally, emerging therapeutic strategies are discussed, including anti-inflammatory agents, metabolic modulators, epigenetic regulators, and regenerative approaches aimed at preserving or restoring β-cell identity in the context of modern metabolic stress.
{"title":"Immunometabolic reprogramming and β-cell dedifferentiation: Integrated mechanisms driving type 2 diabetes progression","authors":"Ritu Dahiya, Ajay Pal Singh, Aruna Rawat","doi":"10.1016/j.diabres.2026.113111","DOIUrl":"10.1016/j.diabres.2026.113111","url":null,"abstract":"<div><div>Type 2 diabetes is increasingly recognised as a condition driven by sustained metabolic overload and chronic low-grade inflammation rather than a simple decline in insulin secretion. Findings from single-cell transcriptomics, human islet studies, and metabolic profiling show that pancreatic β-cells undergo progressive alterations in identity when exposed to glucotoxic, lipotoxic, oxidative, and inflammatory stress. In parallel, cytokines, lipid intermediates, adipose-derived factors, hepatokines, myokines, and gut microbial metabolites generate an immunometabolic environment that accelerates β-cell dedifferentiation and promotes transitions toward progenitor-like or alternative endocrine states. Originally described through lineage-tracing studies in experimental models, β-cell dedifferentiation is now recognized as a dynamic and potentially reversible process shaped by immunometabolic stress in diabetes. This review synthesizes current evidence to illustrate how metabolic and immune pathways converge on key molecular regulators of β-cell fate. It further describes how interorgan communication reinforces these disturbances and contributes to the gradual shift of β-cells along a continuum of stress adaptation, functional decline, and identity loss. A conceptual framework, referred to as the beta-cell identity clock, is presented to capture the dynamic and potentially reversible nature of these transitions. Finally, emerging therapeutic strategies are discussed, including anti-inflammatory agents, metabolic modulators, epigenetic regulators, and regenerative approaches aimed at preserving or restoring β-cell identity in the context of modern metabolic stress.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113111"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.diabres.2026.113116
Lei Gao , Guofu Zhang , Kai Kang , Lei Xu , Wei Zhang , Chao Chi , Erjun Zhu , Taha Sheheryar , Bo Lv , Baodong Xie
Heart failure with preserved ejection fraction (HFpEF) is responsible for approximately half of global heart failure cases and is characterized by marked symptom burden, frequent hospitalization and limited disease-modifying options. Its biology extends beyond the ventricle into vascular, myocardial, metabolic and inflammatory pathways that converge to produce diastolic dysfunction and systemic remodeling. Diagnostic inconsistency and frequent need for exertional testing to unmask elevated filling pressures underscore residual gaps in recognition and targeted therapy. This review synthesizes contemporary evidence spanning epidemiology, mechanisms, diagnostic strategies and phenotype-directed management. Therapeutic advances comprise sodium glucose cotransporter-2 (SGLT2) inhibitors as foundational disease-modifying therapy, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as emerging adjunctive therapy for cardiometabolic HFpEF, structured exercise and lifestyle programs, hemodynamic-guided decongestion and ongoing evaluation of soluble guanylate cyclase (sGC) stimulators. Integrating these insights, HFpEF represents a family of endotypes unified by diastolic dysfunction but driven by distinct systemic mechanisms accounting for variable biomarker profiles and treatment responses. The priorities ahead center on linking human tissue biology with multi-omics and deep clinical phenotyping, standardization of diagnostic criteria, refinement of representative preclinical models and execution of biomarker-enriched, endotype-stratified trials to enable precision prevention and therapy in HFpEF.
{"title":"Heart failure with preserved ejection fraction (HFpEF): translational mechanisms, diagnostic evolution and therapeutic frontiers","authors":"Lei Gao , Guofu Zhang , Kai Kang , Lei Xu , Wei Zhang , Chao Chi , Erjun Zhu , Taha Sheheryar , Bo Lv , Baodong Xie","doi":"10.1016/j.diabres.2026.113116","DOIUrl":"10.1016/j.diabres.2026.113116","url":null,"abstract":"<div><div>Heart failure with preserved ejection fraction (HFpEF) is responsible for approximately half of global heart failure cases and is characterized by marked symptom burden, frequent hospitalization and limited disease-modifying options. Its biology extends beyond the ventricle into vascular, myocardial, metabolic and inflammatory pathways that converge to produce diastolic dysfunction and systemic remodeling. Diagnostic inconsistency and frequent need for exertional testing to unmask elevated filling pressures underscore residual gaps in recognition and targeted therapy. This review synthesizes contemporary evidence spanning epidemiology, mechanisms, diagnostic strategies and phenotype-directed management. Therapeutic advances comprise sodium glucose cotransporter-2 (SGLT2) inhibitors as foundational disease-modifying therapy, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as emerging adjunctive therapy for cardiometabolic HFpEF, structured exercise and lifestyle programs, hemodynamic-guided decongestion and ongoing evaluation of soluble guanylate cyclase (sGC) stimulators. Integrating these insights, HFpEF represents a family of endotypes unified by diastolic dysfunction but driven by distinct systemic mechanisms accounting for variable biomarker profiles and treatment responses. The priorities ahead center on linking human tissue biology with multi-omics and deep clinical phenotyping, standardization of diagnostic criteria, refinement of representative preclinical models and execution of biomarker-enriched, endotype-stratified trials to enable precision prevention and therapy in HFpEF.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113116"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-31DOI: 10.1016/j.diabres.2026.113118
Hanbing Ji , Yutong Wu , Sijia Wu , Xiaoru Sun , Yuanyuan Yu , Lei Hou , Rusong Zhao , Chuan Wang , Yifan Yu , Yilei Ge , Yun Wei , Qingxin Luo , Le Wang , Tiemei Liu , Ziyan Zhang , Jiawei Xiu , Yang Song , Hongkai Li , Shanshan Gao , Fuzhong Xue , Hao Chen
Aims
Metformin is a cost-effective alternative to insulin for gestational diabetes mellitus (GDM), yet concerns regarding potential teratogenicity persist. This study aimed to evaluate the association between prenatal metformin exposure and multisystem congenital malformations (CMs), and to explore biologically relevant pathways.
Methods
This study first conducted a meta-analysis of RCTs and cohort studies assessing maternal metformin use and fetal CMs. Subsequently, drug-target Mendelian randomization (DTMR) examined genetically proxied associations between metformin pharmacodynamic targets (eQTLs) and 64 CMs (FinnGen), reflecting lifelong target perturbation, adjusting for maternal confounders and validating with placental eQTL data.
Results
Meta-analysis showed a protective effect of metformin versus insulin on overall CMs (RR = 0.83, 95% CI 0.71–0.99). In DTMR, following Bonferroni correction and covariate adjustment, seven of 92 target genes (e.g., NDUFS5, NDUFA2) showed significant associations, primarily exhibiting protective effects against circulatory and musculoskeletal system. Validation in placental eQTLs corroborated the direction of effects for 17 gene-outcome pairs, reinforcing the robustness of key safety signals.
Conclusion
By integrating clinical and genetic evidence, this study is consistent with the overall clinical safety of metformin use during pregnancy with respect to congenital malformations and provides hypothesis-generating insights into relevant biological pathways.
目的：二甲双胍是治疗妊娠糖尿病（GDM）的一种具有成本效益的胰岛素替代品，但对潜在致畸性的担忧仍然存在。本研究旨在评估产前二甲双胍暴露与多系统先天性畸形（CMs）之间的关系，并探索生物学相关途径。方法：本研究首先对评估母体使用二甲双胍和胎儿CMs的随机对照试验和队列研究进行了荟萃分析。随后，药物靶孟德尔随机化（DTMR）检测了二甲双胍药效学靶点（eQTL）和64个CMs （FinnGen）之间的遗传相关性，反映了终身靶点扰动，调整了母体混杂因素，并通过胎盘eQTL数据进行了验证。结果：荟萃分析显示二甲双胍与胰岛素对总体CMs的保护作用（RR = 0.83, 95% CI 0.71-0.99）。在DTMR中，经过Bonferroni校正和协变量调整，92个靶基因中有7个（如NDUFS5、NDUFA2）显示出显著的相关性，主要表现出对循环和肌肉骨骼系统的保护作用。胎盘qtl的验证证实了17个基因结局对的效应方向，增强了关键安全信号的稳健性。结论：综合临床和遗传学证据，本研究与妊娠期使用二甲双胍治疗先天性畸形的总体临床安全性是一致的，并为相关生物学途径提供了假设见解。
{"title":"Impact of metformin use during pregnancy on fetal congenital malformations across 11 organ systems: a meta-analysis and drug-target Mendelian randomization study","authors":"Hanbing Ji , Yutong Wu , Sijia Wu , Xiaoru Sun , Yuanyuan Yu , Lei Hou , Rusong Zhao , Chuan Wang , Yifan Yu , Yilei Ge , Yun Wei , Qingxin Luo , Le Wang , Tiemei Liu , Ziyan Zhang , Jiawei Xiu , Yang Song , Hongkai Li , Shanshan Gao , Fuzhong Xue , Hao Chen","doi":"10.1016/j.diabres.2026.113118","DOIUrl":"10.1016/j.diabres.2026.113118","url":null,"abstract":"<div><h3>Aims</h3><div>Metformin is a cost-effective alternative to insulin for gestational diabetes mellitus (GDM), yet concerns regarding potential teratogenicity persist. This study aimed to evaluate the association between prenatal metformin exposure and multisystem congenital malformations (CMs), and to explore biologically relevant pathways.</div></div><div><h3>Methods</h3><div>This study first conducted a meta-analysis of RCTs and cohort studies assessing maternal metformin use and fetal CMs. Subsequently, drug-target Mendelian randomization (DTMR) examined genetically proxied associations between metformin pharmacodynamic targets (eQTLs) and 64 CMs (FinnGen), reflecting lifelong target perturbation, adjusting for maternal confounders and validating with placental eQTL data.</div></div><div><h3>Results</h3><div>Meta-analysis showed a protective effect of metformin versus insulin on overall CMs (<em>RR</em> = 0.83, 95% CI 0.71–0.99). In DTMR, following Bonferroni correction and covariate adjustment, seven of 92 target genes (e.g., <em>NDUFS5</em>, <em>NDUFA2</em>) showed significant associations, primarily exhibiting protective effects against circulatory and musculoskeletal system. Validation in placental eQTLs corroborated the direction of effects for 17 gene-outcome pairs, reinforcing the robustness of key safety signals.</div></div><div><h3>Conclusion</h3><div>By integrating clinical and genetic evidence, this study is consistent with the overall clinical safety of metformin use during pregnancy with respect to congenital malformations and provides hypothesis-generating insights into relevant biological pathways.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113118"},"PeriodicalIF":7.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-31DOI: 10.1016/j.diabres.2026.113135
Mengyao Guo , Shiyi Chen , Huanyu Wang , Jialin Fang , Mingjia Yang
Background
Leisure-time physical activity (LTPA) and sedentary behavior (SB) are considered important modifiable risk factors for Type 2 diabetes mellitus (T2DM). However, the associations of long-term trajectories of LTPA and LTSB with T2DM risk remains uncertain.
Methods
Leveraging prospective cohort data from the China Health and Nutrition Survey (CHNS), we identified the long-term trajectories of LTPA and LTSB among 7,188 participants from 2004 (31 to 77 years) to 2015 (42 to 88 years) by group-based trajectory modeling. Cox regression was used to assess the associations of LTPA and LTSB trajectories with T2DM.
Results
During a mean follow-up of 9.13 years, 715 new-onset T2DM were identified. Three distinct trajectories were identified for both LTPA and LTSB, respectively. Participants in the high decreasing trajectory, but still remains at a relatively high level of LTPA had a 45% lower risk of T2DM (HR: 0.55; 95% CI: 0.30–0.99), relative to those in the inactive stable trajectory. Conversely, compared with the low stable trajectory, the high increasing trajectory of LTSB had a 130% higher risk of T2DM (HR: 2.30; 95% CI: 1.03–5.10).
Conclusion
This prospective study suggests that maintaining higher levels of LTPA and lower levels of LTSB may reduce the risk of T2DM during middle and late adulthood.
{"title":"Leisure-time physical activity and sedentary behavior trajectories during middle and late adulthood in relation to type 2 diabetes mellitus: An 11-year longitudinal study","authors":"Mengyao Guo , Shiyi Chen , Huanyu Wang , Jialin Fang , Mingjia Yang","doi":"10.1016/j.diabres.2026.113135","DOIUrl":"10.1016/j.diabres.2026.113135","url":null,"abstract":"<div><h3>Background</h3><div>Leisure-time physical activity (LTPA) and sedentary behavior (SB) are considered important modifiable risk factors for Type 2 diabetes mellitus (T2DM). However, the associations of long-term trajectories of LTPA and LTSB with T2DM risk remains uncertain.</div></div><div><h3>Methods</h3><div>Leveraging prospective cohort data from the China Health and Nutrition Survey (CHNS), we identified the long-term trajectories of LTPA and LTSB among 7,188 participants from 2004 (31 to 77 years) to 2015 (42 to 88 years) by group-based trajectory modeling. Cox regression was used to assess the associations of LTPA and LTSB trajectories with T2DM.</div></div><div><h3>Results</h3><div>During a mean follow-up of 9.13 years, 715 new-onset T2DM were identified. Three distinct trajectories were identified for both LTPA and LTSB, respectively. Participants in the high decreasing trajectory, but still remains at a relatively high level of LTPA had a 45% lower risk of T2DM (HR: 0.55; 95% CI: 0.30–0.99), relative to those in the inactive stable trajectory. Conversely, compared with the low stable trajectory, the high increasing trajectory of LTSB had a 130% higher risk of T2DM (HR: 2.30; 95% CI: 1.03–5.10).</div></div><div><h3>Conclusion</h3><div>This prospective study suggests that maintaining higher levels of LTPA and lower levels of LTSB may reduce the risk of T2DM during middle and late adulthood.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113135"},"PeriodicalIF":7.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Whether respiratory syncytial virus (RSV) infection contributes to the development of type 2 diabetes (T2DM) or serves as an early warning indicator of T2DM risk remains unclear.
Methods
The study utilized TriNetX US Collaborative Database between January 1, 2022, and March 31, 2024. Patients with a history of T2DM diagnosis, antidiabetic medication use, or HbA1c ≥ 6.5 were excluded. RSV infection was designated as the index event with propensity score matching. The risk of T2DM was assessed using Cox proportional hazards regression models. Sensitivity analyses were conducted for two periods: 2010–2015 and 2016–2019, and across different databases.
Results
A total of 3,052,016 patients, including 15,205 with RSV (mean age, 51.1 years; 59.9% female) and 3,036,811 without RSV (mean age, 46.9 years; 53.4% female). T2DM incidence was 5.69% in the RSV group vs 2.48% in controls, HR 2.684 [95% CI: 2.378–3.030], E-value 4.81. Risk was significantly increased from infection to 3 and 6 months (HR 3 months: 2.697 [95% CI: 2.332–3.119]; HR 6 months: 2.271 [95% CI: 1.911–2.699]). All sensitivity analyses consistently showed a positive trend.
Conclusions
Our findings suggest an association between RSV infection and subsequent T2DM. Prospective studies and mechanistic investigations are warranted to validate these observations and elucidate the underlying pathways.
{"title":"Risk of type 2 diabetes mellitus after respiratory syncytial viral infection: A retrospective cohort study using US database","authors":"Sunny Ssu-Yu Chen , Tina Ting-An Lin , Yi-Lin Chiang , Chien-Yun Chen , Hui-Yuan Chen , Yao-Min Hung , Renin Chang","doi":"10.1016/j.diabres.2026.113123","DOIUrl":"10.1016/j.diabres.2026.113123","url":null,"abstract":"<div><h3>Objective</h3><div>Whether respiratory syncytial virus (RSV) infection contributes to the development of type 2 diabetes (T2DM) or serves as an early warning indicator of T2DM risk remains unclear.</div></div><div><h3>Methods</h3><div>The study utilized TriNetX US Collaborative Database between January 1, 2022, and March 31, 2024. Patients with a history of T2DM diagnosis, antidiabetic medication use, or HbA1c ≥ 6.5 were excluded. RSV infection was designated as the index event with propensity score matching. The risk of T2DM was assessed using Cox proportional hazards regression models. Sensitivity analyses were conducted for two periods: 2010–2015 and 2016–2019, and across different databases.</div></div><div><h3>Results</h3><div>A total of 3,052,016 patients, including 15,205 with RSV (mean age, 51.1 years; 59.9% female) and 3,036,811 without RSV (mean age, 46.9 years; 53.4% female). T2DM incidence was 5.69% in the RSV group vs 2.48% in controls, HR 2.684 [95% CI: 2.378–3.030], E-value 4.81. Risk was significantly increased from infection to 3 and 6 months (HR 3 months: 2.697 [95% CI: 2.332–3.119]; HR 6 months: 2.271 [95% CI: 1.911–2.699]). All sensitivity analyses consistently showed a positive trend.</div></div><div><h3>Conclusions</h3><div>Our findings suggest an association between RSV infection and subsequent T2DM. Prospective studies and mechanistic investigations are warranted to validate these observations and elucidate the underlying pathways.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113123"},"PeriodicalIF":7.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.diabres.2026.113131
Soree Ryang , Jinmi Kim , Minsoo Kim , Myungsoo Im , Doohwa Kim , Yeong Jin Kim , Hyuk Kang , Young Jin Kim , In Joo Kim , Stephane T. Chung , Michael Bergman , Arthur Sherman , Sang Soo Kim , Joon Ha
Aims: Early identification of individuals at risk for type 2 diabetes (T2D) is essential for prevention. We evaluated a novel model-derived disposition index without insulin (mDI-woI), which requires only glucose values from a three time-point oral glucose tolerance test (OGTT: 0, 60, 120 min).
Methods: Among 5,742 healthy Koreans (age 51.2 ± 8.6 years, BMI 24.5 ± 3.1 kg/m2) followed biennially for up to 14 years with repeated OGTTs, we compared baseline mDI-woI with current diabetes biomarkers and the oral disposition index (oDI) using AUC-ROC analyses.
Results: mDI-woI and mean OGTT glucose (mean G) showed the strongest prediction for incident T2D (AUC = 0.79 each), outperforming fasting plasma glucose (0.67), 1 h-PG (0.77), 2 h-PG (0.72), HbA1c (0.71), and oDI (0.68; all P < 0.001). In individuals who progressed to T2D, baseline mDI-woI, mean G, and 1-PG exceeded their thresholds while fasting and 2 h glucose were still below prediabetes cutoffs, indicating earlier risk detection. Moreover, the novel marker mDI-woI is the earliest one, 4 years earlier than mean G and 4.5 years earlier than 1 h-PG, the next two earliest.
Conclusions: Using only three glucose measurements without measuring insulin, mDI-woI provides a simple, sensitive, and clinically practical early marker that outperforms current diabetes criteria for predicting T2D progression, with strong potential for large-scale studies.
{"title":"A novel disposition index without insulin is an earlier and sensitive predictor of type 2 diabetes than current diagnostic criteria","authors":"Soree Ryang , Jinmi Kim , Minsoo Kim , Myungsoo Im , Doohwa Kim , Yeong Jin Kim , Hyuk Kang , Young Jin Kim , In Joo Kim , Stephane T. Chung , Michael Bergman , Arthur Sherman , Sang Soo Kim , Joon Ha","doi":"10.1016/j.diabres.2026.113131","DOIUrl":"10.1016/j.diabres.2026.113131","url":null,"abstract":"<div><div>Aims: Early identification of individuals at risk for type 2 diabetes (T2D) is essential for prevention. We evaluated a novel model-derived disposition index without insulin (mDI-woI), which requires only glucose values from a three time-point oral glucose tolerance test (OGTT: 0, 60, 120 min).</div><div>Methods: Among 5,742 healthy Koreans (age 51.2 ± 8.6 years, BMI 24.5 ± 3.1 kg/m<sup>2</sup>) followed biennially for up to 14 years with repeated OGTTs, we compared baseline mDI-woI with current diabetes biomarkers and the oral disposition index (oDI) using AUC-ROC analyses.</div><div>Results: mDI-woI and mean OGTT glucose (mean G) showed the strongest prediction for incident T2D (AUC = 0.79 each), outperforming fasting plasma glucose (0.67), 1 h-PG (0.77), 2 h-PG (0.72), HbA1c (0.71), and oDI (0.68; all P < 0.001). In individuals who progressed to T2D, baseline mDI-woI, mean G, and 1-PG exceeded their thresholds while fasting and 2 h glucose were still below prediabetes cutoffs, indicating earlier risk detection. Moreover, the novel marker mDI-woI is the earliest one, 4 years earlier than mean G and 4.5 years earlier than 1 h-PG, the next two earliest.</div><div>Conclusions: Using only three glucose measurements without measuring insulin, mDI-woI provides a simple, sensitive, and clinically practical early marker that outperforms current diabetes criteria for predicting T2D progression, with strong potential for large-scale studies.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113131"},"PeriodicalIF":7.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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