Pub Date : 2026-02-06DOI: 10.1016/j.diabres.2026.113141
Linli Liu, Jun Lin, LinHong Li, Sanshan Wu, Zhang Shen, JinHua Chen, Y Peng, Minlan Lin, Xiafei Ye, Danru Chen, Quping Tan
Aims: We investigated the mediation effects of seven insulin resistance(IR) indices: triglyceride glucose (TyG), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), estimated glucose disposal rate (eGDR), metabolic score for IR, lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) on the associations between reproductive factors and circadian syndrome (CircS) in middle-aged and elderly women.
Methods: This study was conducted using the China Health and Retirement Longitudinal Study (CHARLS) as training set and the English Longitudinal Study on Aging (ELSA) as validation set, with baseline non-CircS individuals. Regression models established causal relationships between reproductive factors and incident CircS. Mediation analysis quantified IR mediation effects. Receiver operating characteristic curves evaluated IR indices' predictive capacity.
Results: The incidence of new-onset CircS was 465 (15.94%) in CHARLS and 291 (11.89%) in ELSA, respectively. The CircS incidence was higher in earlier age at menarche or menopause. Mediation analyses revealed that TyG, TyG-WHtR, TyG-WC, LAP, CVAI, and eGDR mediated the menarche-CircS association, with TyG-WHtR accounting for 14.3% of the mediating effect. The TyG-WHtR cutoff value for predicting CircS was identified 4.507 for early menarche.
Conclusion: Significant inverse relationships were observed between early age at menarche/menopause and increased CircS risk, with IR largely mediating these associations.
{"title":"Reproductive factors, insulin resistance surrogate indices, and circadian syndrome among middle-aged and elderly women a mediation analysis using two-national cohorts.","authors":"Linli Liu, Jun Lin, LinHong Li, Sanshan Wu, Zhang Shen, JinHua Chen, Y Peng, Minlan Lin, Xiafei Ye, Danru Chen, Quping Tan","doi":"10.1016/j.diabres.2026.113141","DOIUrl":"https://doi.org/10.1016/j.diabres.2026.113141","url":null,"abstract":"<p><strong>Aims: </strong>We investigated the mediation effects of seven insulin resistance(IR) indices: triglyceride glucose (TyG), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), estimated glucose disposal rate (eGDR), metabolic score for IR, lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) on the associations between reproductive factors and circadian syndrome (CircS) in middle-aged and elderly women.</p><p><strong>Methods: </strong>This study was conducted using the China Health and Retirement Longitudinal Study (CHARLS) as training set and the English Longitudinal Study on Aging (ELSA) as validation set, with baseline non-CircS individuals. Regression models established causal relationships between reproductive factors and incident CircS. Mediation analysis quantified IR mediation effects. Receiver operating characteristic curves evaluated IR indices' predictive capacity.</p><p><strong>Results: </strong>The incidence of new-onset CircS was 465 (15.94%) in CHARLS and 291 (11.89%) in ELSA, respectively. The CircS incidence was higher in earlier age at menarche or menopause. Mediation analyses revealed that TyG, TyG-WHtR, TyG-WC, LAP, CVAI, and eGDR mediated the menarche-CircS association, with TyG-WHtR accounting for 14.3% of the mediating effect. The TyG-WHtR cutoff value for predicting CircS was identified 4.507 for early menarche.</p><p><strong>Conclusion: </strong>Significant inverse relationships were observed between early age at menarche/menopause and increased CircS risk, with IR largely mediating these associations.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113141"},"PeriodicalIF":7.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140787","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 : 2026-02-06DOI: 10.1016/j.diabres.2026.113144
J Sajnani, M Siavoshi, L Kwan, C S Han
Background: There is an increase incidence of diabetes and anti-hyperglycemic use after COVID-19 infection in non-pregnant adult populations. COVID-19 has also been shown to be associated with adverse pregnancy outcomes such as pre-eclampsia and preterm birth.
Objective: To evaluate if COVID-19 infection during preconception or in early pregnancy is associated with increased risk of gestational diabetes mellitus (GDM) diagnosis.
Study design: We performed a retrospective matched cohort study of patients delivering at two university affiliated hospitals from 6/1/2021 to 12/31/2021, prior to widespread vaccinations or home antigen testing for SARS-CoV-2. We included pregnant individuals aged 18 to 45 who were ≥ 24 weeks gestational age at time of delivery. We excluded those with a history of pre-gestational diabetes, multiple gestation, or prior diagnosis of cystic fibrosis or pancreatic insufficiency. Subjects with confirmed COVID-19 infection during preconception or the first 20 weeks of pregnancy were identified as cases and were matched 1:1 by age and BMI with eligible controls. GDM diagnosis was based on a two-step approach using Carpenter-Coustan criteria. Kruskal-Wallis and Chi-Square tests were performed as appropriate RESULTS: During the study period, 183 cases with prior positive COVID-19 antigen test and 1066 potential controls were identified. One case could not be matched due to an outlier BMI; therefore 182 matched patients were included in each group. The cases were less likely to have public insurance and more likely to have reported thyroid disorder, sleep apnea, or asthma. No differences were seen in GDM incidence between the cases and controls (OR 0.75, 95% CI 0.38-1.46) or based on timing of COVID-19 infection (p = 0.097). No differences were noted in delivery method, obstetrical lacerations, or Apgar scores.
Conclusions: COVID-19 infection in the preconception or early pregnancy period was not associated with increased incidence of GDM.
{"title":"Association of prior COVID-19 infection with gestational diabetes mellitus.","authors":"J Sajnani, M Siavoshi, L Kwan, C S Han","doi":"10.1016/j.diabres.2026.113144","DOIUrl":"https://doi.org/10.1016/j.diabres.2026.113144","url":null,"abstract":"<p><strong>Background: </strong>There is an increase incidence of diabetes and anti-hyperglycemic use after COVID-19 infection in non-pregnant adult populations. COVID-19 has also been shown to be associated with adverse pregnancy outcomes such as pre-eclampsia and preterm birth.</p><p><strong>Objective: </strong>To evaluate if COVID-19 infection during preconception or in early pregnancy is associated with increased risk of gestational diabetes mellitus (GDM) diagnosis.</p><p><strong>Study design: </strong>We performed a retrospective matched cohort study of patients delivering at two university affiliated hospitals from 6/1/2021 to 12/31/2021, prior to widespread vaccinations or home antigen testing for SARS-CoV-2. We included pregnant individuals aged 18 to 45 who were ≥ 24 weeks gestational age at time of delivery. We excluded those with a history of pre-gestational diabetes, multiple gestation, or prior diagnosis of cystic fibrosis or pancreatic insufficiency. Subjects with confirmed COVID-19 infection during preconception or the first 20 weeks of pregnancy were identified as cases and were matched 1:1 by age and BMI with eligible controls. GDM diagnosis was based on a two-step approach using Carpenter-Coustan criteria. Kruskal-Wallis and Chi-Square tests were performed as appropriate RESULTS: During the study period, 183 cases with prior positive COVID-19 antigen test and 1066 potential controls were identified. One case could not be matched due to an outlier BMI; therefore 182 matched patients were included in each group. The cases were less likely to have public insurance and more likely to have reported thyroid disorder, sleep apnea, or asthma. No differences were seen in GDM incidence between the cases and controls (OR 0.75, 95% CI 0.38-1.46) or based on timing of COVID-19 infection (p = 0.097). No differences were noted in delivery method, obstetrical lacerations, or Apgar scores.</p><p><strong>Conclusions: </strong>COVID-19 infection in the preconception or early pregnancy period was not associated with increased incidence of GDM.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113144"},"PeriodicalIF":7.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141446","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}
Type 2 Diabetes (T2D) remains a major global health issue, driven by sedentary lifestyles and aging populations, emphasizing the urgent need for precise diagnostics that allow early detection and personalized monitoring. Traditional blood tests, including glucose and HbA1c measurements, offer limited temporal and molecular information. In contrast, saliva provides a non-invasive, easily accessible biofluid that reflects systemic metabolic changes. Its molecular components, especially extracellular vesicles (EVs), such as exosomes and microvesicles, contain proteins, lipids, and microRNAs directly associated with insulin resistance, β-cell dysfunction, and inflammation in T2D. Advances in Raman spectroscopy and surface-enhanced Raman scattering (SERS) now enable high-sensitivity, label-free molecular fingerprinting of salivary EVs, supporting multiplex detection of disease-related biomarkers. Combining Raman-based sensing with EV profiling introduces an innovative approach for non-invasive, precision diabetes diagnostics. This review explores the diagnostic importance of salivary EVs, recent developments in Raman/SERS-based biomolecular detection, and the clinical potential of integrating these technologies for early screening and therapy monitoring. Moreover, incorporating artificial intelligence (AI) for spectral analysis and developing portable Raman devices could facilitate real-time, saliva-based metabolic monitoring, advancing personalized, preventive, and patient-focused diabetes care.
{"title":"Salivary extracellular vesicles and Raman spectroscopy in precision diagnostics of type 2 diabetes.","authors":"Ajitesh Dhal, Shao-Jung Lin, Arunima Pandey, Chih-Hsuan Liu, Hung-Yi Liu, Tarakanta Jena, Chitralekha Jena, Dharitri Rath, Pei-Wen Peng, Cheng-Jen Chang, Chang-I Chen, Li-Chern Pan, Tzu-Sen Yang","doi":"10.1016/j.diabres.2026.113139","DOIUrl":"https://doi.org/10.1016/j.diabres.2026.113139","url":null,"abstract":"<p><p>Type 2 Diabetes (T2D) remains a major global health issue, driven by sedentary lifestyles and aging populations, emphasizing the urgent need for precise diagnostics that allow early detection and personalized monitoring. Traditional blood tests, including glucose and HbA1c measurements, offer limited temporal and molecular information. In contrast, saliva provides a non-invasive, easily accessible biofluid that reflects systemic metabolic changes. Its molecular components, especially extracellular vesicles (EVs), such as exosomes and microvesicles, contain proteins, lipids, and microRNAs directly associated with insulin resistance, β-cell dysfunction, and inflammation in T2D. Advances in Raman spectroscopy and surface-enhanced Raman scattering (SERS) now enable high-sensitivity, label-free molecular fingerprinting of salivary EVs, supporting multiplex detection of disease-related biomarkers. Combining Raman-based sensing with EV profiling introduces an innovative approach for non-invasive, precision diabetes diagnostics. This review explores the diagnostic importance of salivary EVs, recent developments in Raman/SERS-based biomolecular detection, and the clinical potential of integrating these technologies for early screening and therapy monitoring. Moreover, incorporating artificial intelligence (AI) for spectral analysis and developing portable Raman devices could facilitate real-time, saliva-based metabolic monitoring, advancing personalized, preventive, and patient-focused diabetes care.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113139"},"PeriodicalIF":7.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137411","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}
Background: Diabetic foot ulcers (DFUs) present a major challenge due to impaired angiogenesis and chronic inflammation. Autologous platelet-rich plasma (PRP) is a widely used therapy, but clinical outcomes remain inconsistent. We hypothesized that the microRNA (miRNA) cargo of platelet-derived extracellular vesicles (PRP-EVs) drives this therapeutic variability.
Methods: Ten patients with refractory DFUs were enrolled. Autologous PRP-EVs were isolated, and wound healing-associated miRNAs were quantified via qRT-PCR. Clinical wound closure was monitored weekly, with the primary efficacy endpoint assessed at 6 weeks. The biological effects of patient-specific PRP-EVs on keratinocyte migration were evaluated in vitro.
Results: PRP treatment resulted in significant wound area reduction, achieving an average closure rate of approximately 90% by week 6. However, miRNA expression exhibited substantial heterogeneity. High levels of miR-20a-5p and miR-21-5p in PRP-EVs were significantly associated with delayed clinical healing and impaired keratinocyte migration. Conversely, elevated miR-223-3p correlated with accelerated wound closure.
Conclusion: The intrinsic miRNA composition of PRP-EVs is a critical determinant of PRP therapeutic efficacy. miR-20a-5p and miR-21-5p serve as negative predictive biomarkers, whereas miR-223-3p indicates a favorable prognosis. Profiling these miRNAs offers a novel approach for PRP quality control and personalized regenerative strategies.
{"title":"Distinct microRNA signatures in Platelet-Rich Plasma-Derived extracellular vesicles predict healing outcomes in chronic diabetic foot ulcers.","authors":"Yu-Chi Tsai, Shu-Yu Wu, Chien-Ju Wu, Hao-Yu Chiao, Hsu-Ping Tseng, Yu-Min He, Tim-Mo Chen, Min-Yu Tu, Yuan-Sheng Tzeng","doi":"10.1016/j.diabres.2026.113142","DOIUrl":"https://doi.org/10.1016/j.diabres.2026.113142","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) present a major challenge due to impaired angiogenesis and chronic inflammation. Autologous platelet-rich plasma (PRP) is a widely used therapy, but clinical outcomes remain inconsistent. We hypothesized that the microRNA (miRNA) cargo of platelet-derived extracellular vesicles (PRP-EVs) drives this therapeutic variability.</p><p><strong>Methods: </strong>Ten patients with refractory DFUs were enrolled. Autologous PRP-EVs were isolated, and wound healing-associated miRNAs were quantified via qRT-PCR. Clinical wound closure was monitored weekly, with the primary efficacy endpoint assessed at 6 weeks. The biological effects of patient-specific PRP-EVs on keratinocyte migration were evaluated in vitro.</p><p><strong>Results: </strong>PRP treatment resulted in significant wound area reduction, achieving an average closure rate of approximately 90% by week 6. However, miRNA expression exhibited substantial heterogeneity. High levels of miR-20a-5p and miR-21-5p in PRP-EVs were significantly associated with delayed clinical healing and impaired keratinocyte migration. Conversely, elevated miR-223-3p correlated with accelerated wound closure.</p><p><strong>Conclusion: </strong>The intrinsic miRNA composition of PRP-EVs is a critical determinant of PRP therapeutic efficacy. miR-20a-5p and miR-21-5p serve as negative predictive biomarkers, whereas miR-223-3p indicates a favorable prognosis. Profiling these miRNAs offers a novel approach for PRP quality control and personalized regenerative strategies.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113142"},"PeriodicalIF":7.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131040","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 : 2026-02-04DOI: 10.1016/j.diabres.2026.113140
Georgia Anastasiou, Nikolaos Papanas, Fotios Barkas, Nicholas Tentolouris, Georgios Liamis, Lampros K Michalis, Aris Bechlioulis, Rigas Kalaitzidis, Evangelos Liberopoulos
Aims: 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":"https://doi.org/10.1016/j.diabres.2026.113140","url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>The prevalence of DSPN in prediabetes is not negligible in our study. DSPN is independently associated with central obesity and insulin resistance.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"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.2026.113135
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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113135"},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","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}
<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":"https://doi.org/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.2026.113136
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, Natassia Rodrigo, Yee Wen Kong, 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, Natassia Rodrigo, Yee Wen Kong, David N O'Neal","doi":"10.1016/j.diabres.2026.113136","DOIUrl":"10.1016/j.diabres.2026.113136","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"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}
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":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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%).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"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}