Pub Date : 2026-02-01Epub Date: 2026-01-08DOI: 10.1016/j.diabres.2026.113093
Zhenhua Huang , Yuting Gao , Lixiang Liu , Maolin Li , Qinghua Yuan
Background
Insulin resistance (IR) indices like the TyG index are predictors of type 2 diabetes (T2DM), but their comparative performance across BMI categories in East Asians is unclear.
Methods
This retrospective cohort study enrolled 114,293 Chinese adults without diabetes. Four IR indices (TyG, TyG-BMI, TG/HDL-C, METS-IR) were calculated. Their associations with incident T2DM were assessed using Cox models, restricted cubic splines, and machine learning, stratified by BMI. Findings were replicated in 15,453 Japanese adults from the NAGALA cohort.
Results
Over a mean 3.10-year follow-up, 2,435 participants developed T2DM. All indices were independently associated with diabetes risk, but the association strength declined with higher BMI. For TyG, the fully adjusted hazard ratios were 4.60, 3.10, and 2.62 in the non-overweight, overweight, and obese groups, respectively—a “reverse gradient” observed for all indices. Non-linear relationships with clear inflection points were identified. Predictive performance was highest in the non-overweight group (e.g., TyG AUC 76.74%). External replication confirmed these findings.
Conclusions
IR indices, particularly TyG and TyG-BMI, are powerful predictors of T2DM across all BMI categories. Their predictive ability is most pronounced in non-overweight individuals, challenging the obesity-centric diabetes screening paradigm and underscoring the need for early metabolic risk assessment in lean adults.
{"title":"Association between the insulin resistance indices and incident type 2 diabetes across different body mass index states: a cohort study and external validation from two East Asian populations","authors":"Zhenhua Huang , Yuting Gao , Lixiang Liu , Maolin Li , Qinghua Yuan","doi":"10.1016/j.diabres.2026.113093","DOIUrl":"10.1016/j.diabres.2026.113093","url":null,"abstract":"<div><h3>Background</h3><div>Insulin resistance (IR) indices like the TyG index are predictors of type 2 diabetes (T2DM), but their comparative performance across BMI categories in East Asians is unclear.</div></div><div><h3>Methods</h3><div>This retrospective cohort study enrolled 114,293 Chinese adults without diabetes. Four IR indices (TyG, TyG-BMI, TG/HDL-C, METS-IR) were calculated. Their associations with incident T2DM were assessed using Cox models, restricted cubic splines, and machine learning, stratified by BMI. Findings were replicated in 15,453 Japanese adults from the NAGALA cohort.</div></div><div><h3>Results</h3><div> <!-->Over a mean 3.10-year follow-up, 2,435 participants developed T2DM. All indices were independently associated with diabetes risk, but the association strength declined with higher BMI. For TyG, the fully adjusted hazard ratios were 4.60, 3.10, and 2.62 in the non-overweight, overweight, and obese groups, respectively—a “reverse gradient” observed for all indices. Non-linear relationships with clear inflection points were identified. Predictive performance was highest in the non-overweight group (e.g., TyG AUC 76.74%). External replication confirmed these findings.</div></div><div><h3>Conclusions</h3><div> <!-->IR indices, particularly TyG and TyG-BMI, are powerful predictors of T2DM across all BMI categories. Their predictive ability is most pronounced in non-overweight individuals, challenging the obesity-centric diabetes screening paradigm and underscoring the need for early metabolic risk assessment in lean adults.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113093"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948578","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 : 2026-02-01Epub Date: 2026-01-15DOI: 10.1016/j.diabres.2026.113108
Nick S.R. Lan , Jonathan Hiew , Pamela Chen , Mahalia McEvoy , Priyal Shah , Ivana Ferreira , J. Carsten Ritter , Laurens Manning , Bu B. Yeap , P. Gerry Fegan , Girish Dwivedi , Emma J. Hamilton
Aims
Pedal medial arterial calcification (pMAC) is a marker of vascular pathology incidentally detected on foot x-ray. We assessed the association between pMAC and major adverse cardiovascular events (MACE) and mortality in patients with diabetes-related foot ulceration (DFU).
Methods
A retrospective study of adults with DFU was performed. pMAC was assessed at five sites on foot x-ray and graded as no/low, moderate or severe. Incident MACE was defined as hospitalisation for myocardial infarction, heart failure, stroke or transient ischaemic attack.
Results
Of 509 patients, 55.2%, 23.4% and 21.4% had no/low, moderate and severe pMAC, respectively. Median follow-up was 531 days (interquartile range 288–793). pMAC was associated with higher MACE or all-cause mortality (no/low 18.1% versus moderate 26.9% versus severe 42.2%; log-rank p < 0.001) and MACE (no/low 11.4% versus moderate 19.3% versus severe 19.3%; log-rank p = 0.020). In multivariable analysis, pMAC was associated with MACE or all-cause mortality (p = 0.009), but not MACE (p = 0.299). MACE was highest in patients with both pMAC and infected ulcers (25.0%), compared with pMAC only (12.5%), infection only (14.0%) and neither (9.0%) (log-rank p < 0.001), remaining significant after adjustment (p = 0.017).
Conclusions
pMAC is associated with MACE or all-cause mortality in patients with DFU, with infected ulcers heightening the risk of MACE.
{"title":"Medial arterial calcification of the foot arteries is associated with incident cardiovascular events or all-cause mortality in patients with diabetes-related foot ulceration","authors":"Nick S.R. Lan , Jonathan Hiew , Pamela Chen , Mahalia McEvoy , Priyal Shah , Ivana Ferreira , J. Carsten Ritter , Laurens Manning , Bu B. Yeap , P. Gerry Fegan , Girish Dwivedi , Emma J. Hamilton","doi":"10.1016/j.diabres.2026.113108","DOIUrl":"10.1016/j.diabres.2026.113108","url":null,"abstract":"<div><h3>Aims</h3><div>Pedal medial arterial calcification (pMAC) is a marker of vascular pathology incidentally detected on foot x-ray. We assessed the association between pMAC and major adverse cardiovascular events (MACE) and mortality in patients with diabetes-related foot ulceration (DFU).</div></div><div><h3>Methods</h3><div>A retrospective study of adults with DFU was performed. pMAC was assessed at five sites on foot x-ray and graded as no/low, moderate or severe. Incident MACE was defined as hospitalisation for myocardial infarction, heart failure, stroke or transient ischaemic attack.</div></div><div><h3>Results</h3><div>Of 509 patients, 55.2%, 23.4% and 21.4% had no/low, moderate and severe pMAC, respectively. Median follow-up was 531 days (interquartile range 288–793). pMAC was associated with higher MACE or all-cause mortality (no/low 18.1% versus moderate 26.9% versus severe 42.2%; log-rank p < 0.001) and MACE (no/low 11.4% versus moderate 19.3% versus severe 19.3%; log-rank p = 0.020). In multivariable analysis, pMAC was associated with MACE or all-cause mortality (p = 0.009), but not MACE (p = 0.299). MACE was highest in patients with both pMAC and infected ulcers (25.0%), compared with pMAC only (12.5%), infection only (14.0%) and neither (9.0%) (log-rank p < 0.001), remaining significant after adjustment (p = 0.017).</div></div><div><h3>Conclusions</h3><div>pMAC is associated with MACE or all-cause mortality in patients with DFU, with infected ulcers heightening the risk of MACE.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113108"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994209","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 : 2026-02-01Epub Date: 2026-01-02DOI: 10.1016/j.diabres.2025.113081
Per Lav Madsen , Ikram Mizrak , Martin Heyn Sørensen , Peter Haulund Gæde , Annemie Stege Bojer
Objective
To evaluate if metabolic cardiomyopathy comprises different phenotypes.
Methods
Data-driven cluster analysis with hierarchical clustering followed by gap and silhouette width analysis and clustering by k-means was conducted on cardiovascular variables in a cohort of 192 patients with type 2 diabetes (T2D).
Results
Two distinct clusters were identified. 59 % of patients with DM2 had small left ventricles and atria with normal mass, high heart rate with small stroke volumes, and only moderately impaired myocardial perfusion reserve (3.32 ± 1.20 vs. 5.07 ± 1.51 ml/min/g in normal controls, p < 0.01). With equal e/e and extracellular volumes, other 41 % of patients with T2D had eccentric hypertrophic large left ventricles with dilated left atria, high stroke volumes, and a mean 6 mmHg higher mean arterial blood pressure and mean 15 mmHg higher pulse pressure, lower heart rates and lower myocardial perfusion reserve (2.60 ± 0.87 mL/min/g, P < 0.01 vs. other groups).
Conclusions
Two distinct types of cardiomyopathies were identified. The majority exhibited small left hearts with only moderate impairment in myocardial perfusion ratio. However, when stiff conductance arteries were present, cardiomyopathy with larger and eccentrically hypertrophic left ventricles and markedly reduced myocardial perfusion ratio was observed. Future research should seek to determine if these two phenotypes carry independent prognostic implications and should be treated differently.
目的：评价代谢性心肌病是否包括不同的表型。方法：对192例2型糖尿病（T2D）患者的心血管变量进行数据驱动的分层聚类分析、间隙和轮廓宽度分析以及k-means聚类。结果：鉴定出两个不同的簇。59 %的DM2患者左心室和心房体积小，体积正常，心率高，每搏容量小，心肌灌注储备仅中度受损(正常对照为3.32 ± 1.20 vs. 5.07 ± 1.51 ml/min/g， p 结论：确定了两种不同类型的心肌病。大多数患者左心较小，心肌灌注比仅出现中度损伤。然而，当存在僵硬的传导动脉时，心肌病表现为左心室增大和偏心肥厚，心肌灌注比明显降低。未来的研究应该寻求确定这两种表型是否具有独立的预后意义，是否应该区别对待。
{"title":"Two phenotypes of metabolic cardiomyopathy: Data-driven cluster analysis of non-invasively determined cardiovascular phenotypical traits","authors":"Per Lav Madsen , Ikram Mizrak , Martin Heyn Sørensen , Peter Haulund Gæde , Annemie Stege Bojer","doi":"10.1016/j.diabres.2025.113081","DOIUrl":"10.1016/j.diabres.2025.113081","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate if metabolic cardiomyopathy comprises different phenotypes.</div></div><div><h3>Methods</h3><div>Data-driven cluster analysis with hierarchical clustering followed by gap and silhouette width analysis and clustering by k-means was conducted on cardiovascular variables in a cohort of 192 patients with type 2 diabetes (T2D).</div></div><div><h3>Results</h3><div>Two distinct clusters were identified. 59 % of patients with DM2 had small left ventricles and atria with normal mass, high heart rate with small stroke volumes, and only moderately impaired myocardial perfusion reserve (3.32 ± 1.20 <em>vs</em>. 5.07 ± 1.51 ml/min/g in normal controls, p < 0.01). With equal e/e and extracellular volumes, other 41 % of patients with T2D had eccentric hypertrophic large left ventricles with dilated left atria, high stroke volumes, and a mean 6 mmHg higher mean arterial blood pressure and mean 15 mmHg higher pulse pressure, lower heart rates and lower myocardial perfusion reserve (2.60 ± 0.87 mL/min/g, P < 0.01 <em>vs</em>. other groups).</div></div><div><h3>Conclusions</h3><div>Two distinct types of cardiomyopathies were identified. The majority exhibited small left hearts with only moderate impairment in myocardial perfusion ratio. However, when stiff conductance arteries were present, cardiomyopathy with larger and eccentrically hypertrophic left ventricles and markedly reduced myocardial perfusion ratio was observed. Future research should seek to determine if these two phenotypes carry independent prognostic implications and should be treated differently.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113081"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899410","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 : 2026-02-01Epub Date: 2026-01-06DOI: 10.1016/j.diabres.2026.113084
Tomás P Griffin , Jennifer Hagan , Radhika Chauhan , Thomas SJ Crabtree , Dawn Ackroyd , Jackie Elliott , Parth Narendran , Zosanglura Bawlchhim , Emma G Wilmot , Michelle Hadjiconstantinou , Pratik Choudhary
Aims
This study evaluated the impact of ≥3 months of HCL use on patient-reported outcomes (PROs) in PwT1D and their partners.
Methods
Participants enrolled on the NHS England HCL pilot were invited to take part in a mixed-methods study. Here, we present the results of the quantitative study. PwT1D completed online questionnaires, including INSPIRE (0–100), DTSQc (−18 to +18), System Usability Scale (0–100), and bespoke measures. Self-reported clinical data were collected. Optionally, partners completed the INSPIRE for partners questionnaire.
Results
A total of 125 PwT1D and 33 partners participated. PROs included: INSPIRE 88/100 (IQR 73–95) and DTSQc 17/18(14–18). In INSPIRE, >70 % strongly agree that HCL improved HbA1c, time in range and overall quality of life. In DTSQc, >70 % noted that their blood glucose levels had been unacceptably low/high much less of the time since starting HCL. However, 54.4 % reported increased alarm burden and 21.6 % information overload. People who found HCL harder to use based on the SUS score had lower INSPIRE, DTSQs and DTSQc scores and higher HbA1c than those who found HCL easier to use.
Conclusions
HCL therapy is associated with improved PROs in PwT1D. However, system usability significantly influences outcomes, and alarm and data burden remain concerns.
{"title":"The results of ProHCL: Patient-reported outcomes in people living with type 1 diabetes on hybrid closed-loop insulin pump therapy − experiences from the NHS England pilot","authors":"Tomás P Griffin , Jennifer Hagan , Radhika Chauhan , Thomas SJ Crabtree , Dawn Ackroyd , Jackie Elliott , Parth Narendran , Zosanglura Bawlchhim , Emma G Wilmot , Michelle Hadjiconstantinou , Pratik Choudhary","doi":"10.1016/j.diabres.2026.113084","DOIUrl":"10.1016/j.diabres.2026.113084","url":null,"abstract":"<div><h3>Aims</h3><div>This study evaluated the impact of ≥3 months of HCL use on patient-reported outcomes (PROs) in PwT1D and their partners.</div></div><div><h3>Methods</h3><div>Participants enrolled on the NHS England HCL pilot were invited to take part in a mixed-methods study. Here, we present the results of the quantitative study. PwT1D completed online questionnaires, including INSPIRE (0–100), DTSQc (−18 to +18), System Usability Scale (0–100), and bespoke measures. Self-reported clinical data were collected. Optionally, partners completed the INSPIRE for partners questionnaire.</div></div><div><h3>Results</h3><div>A total of 125 PwT1D and 33 partners participated. PROs included: INSPIRE 88/100 (IQR 73–95) and DTSQc 17/18(14–18). In INSPIRE, >70 % strongly agree that HCL improved HbA1c, time in range and overall quality of life. In DTSQc, >70 % noted that their blood glucose levels had been unacceptably low/high much less of the time since starting HCL. However, 54.4 % reported increased alarm burden and 21.6 % information overload. People who found HCL harder to use based on the SUS score had lower INSPIRE, DTSQs and DTSQc scores and higher HbA1c than those who found HCL easier to use.</div></div><div><h3>Conclusions</h3><div>HCL therapy is associated with improved PROs in PwT1D. However, system usability significantly influences outcomes, and alarm and data burden remain concerns.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113084"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932739","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 : 2026-02-01Epub Date: 2026-01-14DOI: 10.1016/j.diabres.2026.113107
Xiaoqin Zhou , Weiqiang Ruan , Jianfeng Pu , Jinmei Zhang , Chuanya Pang , Shuhua Luo , Jing Li
Aims
To analyze 25-year trends (1999–2023) in cardiovascular mortality among U.S. adults ≥ 65 years with type 2 diabetes.
Methods
Using CDC WONDER data, we assessed age-adjusted mortality rates (AAMR) for cardiovascular deaths with type 2 diabetes as a contributing cause, stratified by sex, age group, race/ethnicity, and geographic region.
Results
Between 1999–2023, 529,472 cardiovascular deaths occurred among older adults with type 2 diabetes. AAMR increased significantly from 40.58 to 66.93 per 100,000 population. A dramatic acceleration occurred during 2019–2021 with a 26.2% mortality increase, coinciding with the COVID-19 pandemic. Men consistently demonstrated higher AAMR and steeper increases. Hispanic older adults shifted from third-highest to the highest AAMR by 2023. States with elevated mortality concentrated in the West and Midwest regions. Atherosclerotic heart disease remained the leading cause, while atrial fibrillation emerged as the 5th leading cause with a 624.7% increase in AAMR.
Conclusions
Cardiovascular mortality among older adults with type 2 diabetes increased over 25 years, with a devastating acceleration during 2019–2021 that temporally coincided with the COVID-19 pandemic. Persistent sex-, racial-, and geographic-based disparities, combined with evolving cardiovascular mortality patterns, underscore the imperative for targeted interventions addressing the fundamental social determinants of health underlying these inequities.
{"title":"Cardiovascular mortality trends and disparities among older adults (≥65 years) with type 2 diabetes in the United States: a CDC WONDER database analysis, 1999–2023","authors":"Xiaoqin Zhou , Weiqiang Ruan , Jianfeng Pu , Jinmei Zhang , Chuanya Pang , Shuhua Luo , Jing Li","doi":"10.1016/j.diabres.2026.113107","DOIUrl":"10.1016/j.diabres.2026.113107","url":null,"abstract":"<div><h3>Aims</h3><div>To analyze 25-year trends (1999–2023) in cardiovascular mortality among U.S. adults ≥ 65 years with type 2 diabetes.</div></div><div><h3>Methods</h3><div>Using CDC WONDER data, we assessed age-adjusted mortality rates (AAMR) for cardiovascular deaths with type 2 diabetes as a contributing cause, stratified by sex, age group, race/ethnicity, and geographic region.</div></div><div><h3>Results</h3><div>Between 1999–2023, 529,472 cardiovascular deaths occurred among older adults with type 2 diabetes. AAMR increased significantly from 40.58 to 66.93 per 100,000 population. A dramatic acceleration occurred during 2019–2021 with a 26.2% mortality increase, coinciding with the COVID-19 pandemic. Men consistently demonstrated higher AAMR and steeper increases. Hispanic older adults shifted from third-highest to the highest AAMR by 2023. States with elevated mortality concentrated in the West and Midwest regions. Atherosclerotic heart disease remained the leading cause, while atrial fibrillation emerged as the 5th leading cause with a 624.7% increase in AAMR.</div></div><div><h3>Conclusions</h3><div>Cardiovascular mortality among older adults with type 2 diabetes increased over 25 years, with a devastating acceleration during 2019–2021 that temporally coincided with the COVID-19 pandemic. Persistent sex-, racial-, and geographic-based disparities, combined with evolving cardiovascular mortality patterns, underscore the imperative for targeted interventions addressing the fundamental social determinants of health underlying these inequities.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113107"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974483","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 : 2026-02-01Epub Date: 2026-01-21DOI: 10.1016/j.diabres.2026.113109
Siqi Jia , Qingping Zeng , Ping Zhu , Feng Liu
Background
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are widely used for the management of type 2 diabetes mellitus (T2DM) and heart failure (HF). SGLT-2 inhibitors reduce cardiovascular events in T2DM, but concerns persist about diabetic foot infection (DFI).
Objective
To quantify the association between individual SGLT-2 inhibitors and DFI using real-world pharmacovigilance data.
Methods
The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports (2004 Q1–2024 Q2) were screened; 62 098 records listed an SGLT-2 inhibitor as the “primary suspect” drug. DFI was identified via eight Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) plus 324 MedDRA Preferred Terms (PTs). Disproportionality was evaluated by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM); only “primary suspect” events were retained.
Results
Among 8 312 293 reports, 565 DFI cases implicated an SGLT-2 inhibitor. Canagliflozin showed the highest signal (ROR 162.84; 95 % CI 134.14–197.68), whereas empagliflozin (ROR 0.56) and dapagliflozin (ROR 2.19) did not reach positive criteria. The class-level ROR was 55.51 (45.18–68.21). Additionally, this study examined the time-dependent association between SGLT-2 inhibitors and DFI. The results indicated a significant increase in the ROR for DFI with increasing duration of exposure: the ROR was 11.25 (95% CI: 8.14–15.56) when the exposure duration was ≤30 days; it escalated to 48.77 (95% CI: 39.88–59.64) when the exposure duration exceeded 365 days. The EBGM analysis further corroborated this time-dependent signal, demonstrating that as the duration of exposure lengthened, the envelope of the EBGM and its 95%CI (EBO5/EB95) progressively intensified.
Conclusions
A strong, agent-specific signal links canagliflozin to DFI. Clinicians should prioritise foot surveillance and consider safer SGLT-2 inhibitor alternatives in high-risk patients.
{"title":"Pharmacovigilance analysis of the association between SGLT-2 inhibitors and diabetic foot infections using the FAERS database: An observational study","authors":"Siqi Jia , Qingping Zeng , Ping Zhu , Feng Liu","doi":"10.1016/j.diabres.2026.113109","DOIUrl":"10.1016/j.diabres.2026.113109","url":null,"abstract":"<div><h3>Background</h3><div>Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are widely used for the management of type 2 diabetes mellitus (T2DM) and heart failure (HF). SGLT-2 inhibitors reduce cardiovascular events in T2DM, but concerns persist about diabetic foot infection (DFI).</div></div><div><h3>Objective</h3><div>To quantify the association between individual SGLT-2 inhibitors and DFI using real-world pharmacovigilance data.</div></div><div><h3>Methods</h3><div>The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports (2004 Q1–2024 Q2) were screened; 62 098 records listed an SGLT-2 inhibitor as the “primary suspect” drug. DFI was identified via eight Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) plus 324 MedDRA Preferred Terms (PTs). Disproportionality was evaluated by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM); only “primary suspect” events were retained.</div></div><div><h3>Results</h3><div>Among 8 312 293 reports, 565 DFI cases implicated an SGLT-2 inhibitor. Canagliflozin showed the highest signal (ROR 162.84; 95 % CI 134.14–197.68), whereas empagliflozin (ROR 0.56) and dapagliflozin (ROR 2.19) did not reach positive criteria. The class-level ROR was 55.51 (45.18–68.21). Additionally, this study examined the time-dependent association between SGLT-2 inhibitors and DFI. The results indicated a significant increase in the ROR for DFI with increasing duration of exposure: the ROR was 11.25 (95% CI: 8.14–15.56) when the exposure duration was ≤30 days; it escalated to 48.77 (95% CI: 39.88–59.64) when the exposure duration exceeded 365 days. The EBGM analysis further corroborated this time-dependent signal, demonstrating that as the duration of exposure lengthened, the envelope of the EBGM and its 95%CI (EBO5/EB95) progressively intensified.</div></div><div><h3>Conclusions</h3><div>A strong, agent-specific signal links canagliflozin to DFI. Clinicians should prioritise foot surveillance and consider safer SGLT-2 inhibitor alternatives in high-risk patients.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113109"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035265","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 : 2026-02-01Epub Date: 2025-12-20DOI: 10.1016/j.diabres.2025.113063
Jennifer A. Andersen , Pearl A. McElfish , James P. Selig , Ji Li , Brett Rowland , Jonell Hudson , Shashank Kraleti , Joseph Henske , Lindsay S. Mayberry
Aims
Family members/support persons can shape the self-management decisions of persons with T2DM (PWDs), and their inclusion in DSMES may lead to improved outcomes. However, research on the effectiveness of family models of DSMES (Family-DSMES) is limited. We conducted a comparative effectiveness-implementation RCT of Family-DSMES and a standard model of DSMES (Standard-DSMES) delivered via telehealth.
Methods
550 diverse adult PWDs and their family members/support persons were recruited from eight primary care clinics in both rural and urban areas. Process data was collected to evaluate implementation characteristics. Biometric, behavioral, and psychosocial measures were collected from PWDs.
Results
Mean attendance was slightly higher for PWDs in Family-DSMES than Standard-DSMES (62 % vs. 57 %, p = 0.096). Engagement (p = 0.319) and class time (p = 0.145) were similar across arms. PWDs in both arms experienced a decrease in HbA1c at all time points (p < 0.005). No statistically significant between-arm differences were found for biometric outcomes or behavioral outcomes including HbA1c. For diabetes-related helpful family involvement, the improvement in the Family-DSMES arm was significantly greater than in the Standard-DSMES arm (p = 0.024).
Conclusions
Results demonstrate the ability to engage rural and diverse PWDs in a telehealth intervention with high fidelity to achieve clinically and statistically significant improvements in HbA1c.
{"title":"Comparative effectiveness of telehealth-delivered family and standard models of diabetes self-management education and support for persons with type 2 diabetes mellitus","authors":"Jennifer A. Andersen , Pearl A. McElfish , James P. Selig , Ji Li , Brett Rowland , Jonell Hudson , Shashank Kraleti , Joseph Henske , Lindsay S. Mayberry","doi":"10.1016/j.diabres.2025.113063","DOIUrl":"10.1016/j.diabres.2025.113063","url":null,"abstract":"<div><h3>Aims</h3><div>Family members/support persons can shape the self-management decisions of persons with T2DM (PWDs), and their inclusion in DSMES may lead to improved outcomes. However, research on the effectiveness of family models of DSMES (Family-DSMES) is limited. We conducted a comparative effectiveness-implementation RCT of Family-DSMES and a standard model of DSMES (Standard-DSMES) delivered via telehealth.</div></div><div><h3>Methods</h3><div>550 diverse adult PWDs and their family members/support persons were recruited from eight primary care clinics in both rural and urban areas. Process data was collected to evaluate implementation characteristics. Biometric, behavioral, and psychosocial measures were collected from PWDs.</div></div><div><h3>Results</h3><div>Mean attendance was slightly higher for PWDs in Family-DSMES than Standard-DSMES (62 % vs. 57 %, <em>p</em> = 0.096). Engagement (<em>p</em> = 0.319) and class time (<em>p</em> = 0.145) were similar across arms. PWDs in both arms experienced a decrease in HbA1c at all time points (<em>p</em> < 0.005). No statistically significant between-arm differences were found for biometric outcomes or behavioral outcomes including HbA1c. For diabetes-related helpful family involvement, the improvement in the Family-DSMES arm was significantly greater than in the Standard-DSMES arm (<em>p</em> = 0.024).</div></div><div><h3>Conclusions</h3><div>Results demonstrate the ability to engage rural and diverse PWDs in a telehealth intervention with high fidelity to achieve clinically and statistically significant improvements in HbA1c.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113063"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809598","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 : 2026-02-01Epub Date: 2026-01-18DOI: 10.1016/j.diabres.2026.113110
Sayali S. Deshpande-Joshi , Sonali S. Wagle-Patki , Madhura K. Deshmukh , Himangi G. Lubree , Hemant S. Damle , Suhas R. Otiv , Sanat B. Phatak , Rucha H. Wagh , Shrreya S. Sudade , K. Meenakumari , Smita N. Dhadge , Rajashree P. Kamat , Sayali G. Wadke , Deepa A. Raut , Dattatray S. Bhat , Souvik Bandyopadhyay , Chittaranjan S. Yajnik
Aim
To examine relative influence of maternal diabetes and obesity on neonatal size and adiposity in lean Indian population.
Methods
We analyzed routine clinical data collected in one diabetes clinic. Using ANCOVA (Analysis of Covariance), we examined the association of maternal diabetes and overweight-obesity with neonatal weight, abdominal circumference, and skinfold thickness.
Results
We included 772 pregnancies with diabetes (61-type 1, 79-type 2, 632-gestational diabetes mellites (GDM)) and 349 with normal glucose tolerance (NGT). Maternal type of diabetes and overweight-obesity were independently associated with larger neonatal size and adiposity, with a stronger influence of diabetes. Mothers with type 1 diabetes had lowest Body Mass Index (BMI) and highest Glycated hemoglobin (HbA1c) however, their neonates had highest weight, abdominal circumferences, and skinfolds. Compared to neonates of NGT mothers, those of type 1 diabetes were 300 g heavier, of type 2 diabetes 174 g, and of GDM by 111 g. Neonates of overweight-obese mothers were 128 g heavier than those of non-overweight mothers. Gestational weight gain (GWG) was not associated. Similar findings were seen for abdominal circumference and skinfolds.
Conclusion
In an Indian clinic, maternal glycaemia had a much stronger effect on neonatal adiposity compared to her overweight-obesity. Adequate control of maternal hyperglycemia will help control neonatal adiposity.
{"title":"Neonatal adiposity is predominantly influenced by maternal hyperglycemia than obesity: Evidence from India","authors":"Sayali S. Deshpande-Joshi , Sonali S. Wagle-Patki , Madhura K. Deshmukh , Himangi G. Lubree , Hemant S. Damle , Suhas R. Otiv , Sanat B. Phatak , Rucha H. Wagh , Shrreya S. Sudade , K. Meenakumari , Smita N. Dhadge , Rajashree P. Kamat , Sayali G. Wadke , Deepa A. Raut , Dattatray S. Bhat , Souvik Bandyopadhyay , Chittaranjan S. Yajnik","doi":"10.1016/j.diabres.2026.113110","DOIUrl":"10.1016/j.diabres.2026.113110","url":null,"abstract":"<div><h3>Aim</h3><div>To examine relative influence of maternal diabetes and obesity on neonatal size and adiposity in lean Indian population.</div></div><div><h3>Methods</h3><div>We analyzed routine clinical data collected in one diabetes clinic. Using ANCOVA (Analysis of Covariance), we examined the association of maternal diabetes and overweight-obesity with neonatal weight, abdominal circumference, and skinfold thickness.</div></div><div><h3>Results</h3><div>We included 772 pregnancies with diabetes (61-type 1, 79-type 2, 632-gestational diabetes mellites (GDM)) and 349 with normal glucose tolerance (NGT). Maternal type of diabetes and overweight-obesity were independently associated with larger neonatal size and adiposity, with a stronger influence of diabetes. Mothers with type 1 diabetes had lowest Body Mass Index (BMI) and highest Glycated hemoglobin (HbA1c) however, their neonates had highest weight, abdominal circumferences, and skinfolds. Compared to neonates of NGT mothers, those of type 1 diabetes were 300 g heavier, of type 2 diabetes 174 g, and of GDM by 111 g. Neonates of overweight-obese mothers were 128 g heavier than those of non-overweight mothers. Gestational weight gain (GWG) was not associated. Similar findings were seen for abdominal circumference and skinfolds.</div></div><div><h3>Conclusion</h3><div>In an Indian clinic, maternal glycaemia had a much stronger effect on neonatal adiposity compared to her overweight-obesity. Adequate control of maternal hyperglycemia will help control neonatal adiposity.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"232 ","pages":"Article 113110"},"PeriodicalIF":7.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009206","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 : 2026-01-01Epub Date: 2025-11-24DOI: 10.1016/j.diabres.2025.113018
Kanchana Perera , John Baker , Kalpa Jayanatha , Karen Pickering , Richard Cutfield , Brandon Orr-Walker , Gerhard Sundborn , Andrew Heroy , Thomas Arnold ScM , Dahai Yu , David Simmons
Aim
Māori and Pacific adults in New Zealand (NZ) with type 2 diabetes are at high risk of Diabetic Kidney Disease (DKD). This study assessed whether the same was true in young-onset type 2 diabetes.
Methods
We conducted a secondary analysis of young adults 18–40 years enrolled in a (1994–2018) NZ primary care cohort. DKD risk was classified as minimal or elevated using Urine Albumin-Creatinine Ratio (UACR) and Estimated Glomerular Filtration Rate (eGFR), with hyperfiltration (eGFR ≥ 120 mL/min/1.73 m2) considered an early marker. Logistic regression identified predictors of elevated DKD risk.
Results
Among 2,184 participants (46 % Pacific people, 31 % Māori, 23 % NZ European: 54 % female, mean age 33.9 ± 4.9 years, mean BMI 38.0 ± 8.7 kg/m2, diabetes duration 1.7 years), elevated DKD risk was more common in Pacific People (37.4 %) and Māori (33.5 %) than NZE (23.3 %; p < 0.001) with adjusted odds ratio (vs NZE) of 1.96 (95 % CI: 1.50–2.57) and 1.41 (1.06–1.87) respectively. Māori had less risk than Pasifika (odds ratio 0.72 (0.58–0.89)). Independent predictors of DKD risk included ethnicity, triglyceride-HDL ratio, systolic blood pressure, antihypertensive use, and HbA1c: BMI was not significant.
Conclusions
Pacific and Māori with young-onset type 2 diabetes face a disproportionately higher DKD risk.
{"title":"Ethnic differences in risk of renal disease progression amongst young-onset type 2 diabetes in New Zealand","authors":"Kanchana Perera , John Baker , Kalpa Jayanatha , Karen Pickering , Richard Cutfield , Brandon Orr-Walker , Gerhard Sundborn , Andrew Heroy , Thomas Arnold ScM , Dahai Yu , David Simmons","doi":"10.1016/j.diabres.2025.113018","DOIUrl":"10.1016/j.diabres.2025.113018","url":null,"abstract":"<div><h3>Aim</h3><div>Māori and Pacific adults in New Zealand (NZ) with type 2 diabetes are at high risk of Diabetic Kidney Disease (DKD). This study assessed whether the same was true in young-onset type 2 diabetes.</div></div><div><h3>Methods</h3><div>We conducted a secondary analysis of young adults 18–40 years enrolled in a (1994–2018) NZ primary care cohort. DKD risk was classified as minimal or elevated using Urine Albumin-Creatinine Ratio (UACR) and Estimated Glomerular Filtration Rate (eGFR), with hyperfiltration (eGFR ≥ 120 mL/min/1.73 m<sup>2</sup>) considered an early marker. Logistic regression identified predictors of elevated DKD risk.</div></div><div><h3>Results</h3><div>Among 2,184 participants (46 % Pacific people, 31 % Māori, 23 % NZ European: 54 % female, mean age 33.9 ± 4.9 years, mean BMI 38.0 ± 8.7 kg/m<sup>2</sup>, diabetes duration 1.7 years), elevated DKD risk was more common in Pacific People (37.4 %) and Māori (33.5 %) than NZE (23.3 %; <em>p</em> < 0.001) with adjusted odds ratio (vs NZE) of 1.96 (95 % CI: 1.50–2.57) and 1.41 (1.06–1.87) respectively. Māori had less risk than Pasifika (odds ratio 0.72 (0.58–0.89)). Independent predictors of DKD risk included ethnicity, triglyceride-HDL ratio, systolic blood pressure, antihypertensive use, and HbA<sub>1c</sub>: BMI was not significant.</div></div><div><h3>Conclusions</h3><div>Pacific and Māori with young-onset type 2 diabetes face a disproportionately higher DKD risk.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113018"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616573","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}
Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Although hyperglycemia and hypertension are well-established drivers of DKD, accumulating evidence suggests that additional factors, such as lipoprotein(a) [Lp(a)], may contribute to its pathogenesis. Lp(a) is a genetically determined lipoprotein with pro-atherogenic, pro-inflammatory, and pro-thrombotic properties, and elevated circulating levels have been associated with increased cardiovascular and renal risk in diabetic individuals. In this review, we summarize the current understanding of the relationship between Lp(a) and DKD, with a focus on the proposed molecular mechanisms. These include activation of TGF-β/Smad signaling leading to fibrosis, induction of oxidative stress, chronic inflammation, endothelial dysfunction, impaired fibrinolysis, and direct injury to podocytes resulting in proteinuria. While several clinical and experimental studies support the involvement of Lp(a) in these pathways, the precise molecular mediators remain largely undefined. Understanding these mechanisms may offer novel insights into the pathophysiology of DKD and identify new therapeutic targets. This article aims to provide a comprehensive overview of the potential role of Lp(a) in DKD and to highlight areas requiring further investigation.
{"title":"The Emerging role of lipoprotein(a) in diabetic kidney disease: possible pathophysiological links and unresolved mechanisms","authors":"Habib Yaribeygi , Mina Maleki , Sercan Karav , Prashant Kesharwani , Amirhossein Sahebkar","doi":"10.1016/j.diabres.2025.113040","DOIUrl":"10.1016/j.diabres.2025.113040","url":null,"abstract":"<div><div>Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes mellitus and a leading cause of end-stage renal disease worldwide. Although hyperglycemia and hypertension are well-established drivers of DKD, accumulating evidence suggests that additional factors, such as lipoprotein(a) [Lp(a)], may contribute to its pathogenesis. Lp(a) is a genetically determined lipoprotein with pro-atherogenic, pro-inflammatory, and pro-thrombotic properties, and elevated circulating levels have been associated with increased cardiovascular and renal risk in diabetic individuals. In this review, we summarize the current understanding of the relationship between Lp(a) and DKD, with a focus on the proposed molecular mechanisms. These include activation of TGF-β/Smad signaling leading to fibrosis, induction of oxidative stress, chronic inflammation, endothelial dysfunction, impaired fibrinolysis, and direct injury to podocytes resulting in proteinuria. While several clinical and experimental studies support the involvement of Lp(a) in these pathways, the precise molecular mediators remain largely undefined. Understanding these mechanisms may offer novel insights into the pathophysiology of DKD and identify new therapeutic targets. This article aims to provide a comprehensive overview of the potential role of Lp(a) in DKD and to highlight areas requiring further investigation.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113040"},"PeriodicalIF":7.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687336","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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