Pub Date : 2025-08-18DOI: 10.1016/j.jdiacomp.2025.109153
Kelsey A. Schmittling
Lower extremity amputation (LEA) is a costly complication of diabetes, with disproportionate impacts among socially and medically vulnerable populations. While clinical predictors of LEA are well established, the role of behavioral health comorbidities, particularly alongside socioeconomic disparities, in amputation risk is unexplored. To evaluate sociodemographic and behavioral health predictors of LEA, a retrospective analysis of adult patients with diabetes was performed utilizing the Nationwide Inpatient Sample from 2018 to 2022. Sociodemographic and behavioral health characteristics were compared between patients that did and did not undergo LEA. Multivariable logistic regression was used to identify independent predictors of LEA using 2018–2021 data and was then tested on the 2022 validation cohort. Among 7.5 million adult patients with diabetes with inpatient events, patients undergoing LEA were significantly younger, more likely to be male, from lower income quartiles, and disproportionately Black, Hispanic, and Native American (p < 0.001). Substance use disorder was significantly more common among LEA patients (16.0 % vs 11.6 %). In adjusted analysis, several behavioral health conditions were independently associated with increased LEA risk. The model demonstrated modest predictive performance in the testing cohort (AUC = 0.658). While not yet suitable for standalone clinical use, this model highlights that behavioral risk factors, especially in the context of sociodemographic characteristics, warrants increased attention in limb preservation strategies.
下肢截肢（LEA）是一种代价高昂的糖尿病并发症，对社会和医学上脆弱的人群产生了不成比例的影响。虽然LEA的临床预测指标已经确立，但行为健康合并症，特别是与社会经济差异一起，在截肢风险中的作用尚未探索。为了评估LEA的社会人口学和行为健康预测因素，我们利用2018年至2022年全国住院患者样本对成年糖尿病患者进行了回顾性分析。比较了接受LEA和未接受LEA患者的社会人口学和行为健康特征。使用2018-2021年的数据，使用多变量逻辑回归识别LEA的独立预测因子，然后在2022年的验证队列中进行测试。在750万有住院事件的成年糖尿病患者中，接受LEA的患者明显更年轻，更有可能是男性，来自较低收入的四分之一，不成比例地是黑人、西班牙裔和美洲原住民（p < 0.001）。物质使用障碍在LEA患者中更为常见（16.0% vs 11.6%）。在调整分析中，几种行为健康状况与LEA风险增加独立相关。该模型在测试队列中表现出适度的预测性能（AUC = 0.658）。虽然还不适合单独的临床使用，但该模型强调了行为风险因素，特别是在社会人口学特征的背景下，需要在肢体保存策略中增加关注。
{"title":"Risk assessment modeling for diabetes-related lower extremity amputation using socioeconomic and behavioral health indicators","authors":"Kelsey A. Schmittling","doi":"10.1016/j.jdiacomp.2025.109153","DOIUrl":"10.1016/j.jdiacomp.2025.109153","url":null,"abstract":"<div><div>Lower extremity amputation (LEA) is a costly complication of diabetes, with disproportionate impacts among socially and medically vulnerable populations. While clinical predictors of LEA are well established, the role of behavioral health comorbidities, particularly alongside socioeconomic disparities, in amputation risk is unexplored. To evaluate sociodemographic and behavioral health predictors of LEA, a retrospective analysis of adult patients with diabetes was performed utilizing the Nationwide Inpatient Sample from 2018 to 2022. Sociodemographic and behavioral health characteristics were compared between patients that did and did not undergo LEA. Multivariable logistic regression was used to identify independent predictors of LEA using 2018–2021 data and was then tested on the 2022 validation cohort. Among 7.5 million adult patients with diabetes with inpatient events, patients undergoing LEA were significantly younger, more likely to be male, from lower income quartiles, and disproportionately Black, Hispanic, and Native American (<em>p</em> < 0.001). Substance use disorder was significantly more common among LEA patients (16.0 % vs 11.6 %). In adjusted analysis, several behavioral health conditions were independently associated with increased LEA risk. The model demonstrated modest predictive performance in the testing cohort (AUC = 0.658). While not yet suitable for standalone clinical use, this model highlights that behavioral risk factors, especially in the context of sociodemographic characteristics, warrants increased attention in limb preservation strategies.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109153"},"PeriodicalIF":3.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863837","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 : 2025-08-14DOI: 10.1016/j.jdiacomp.2025.109151
Jing Tian , Chenming Zhao, Yulu Li, Yi Han
Glycaemic variability (GV) may reflect sharp rises and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. The aim of this study was to investigate the effect of GV on 28-day outcome in patients with cardiogenic shock (CS) with or without diabetes mellitus (DM).
Methods
This retrospective cohort study adhered to the RECORD (REporting of studies Conducted using Observational Routinely-collected Data) guidelines. We used clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. GV was assessed using the coefficient of variation of blood glucose levels and statistically analysed by dividing patients into three groups according to GV tertiles (GV1, GV2 and GV3), with a primary outcome of 28-day prognosis and secondary outcomes of mechanical ventilation status, length of hospital stay and length of ICU stay.
Results
A total of 1091 patients from the MIMIC-IV database with CS were included, of which a total of 409 (37.49 %) were male patients and 682 (62.51 %) were female patients. Based on GV levels, three groups were classified as GV1 (<16.2 %, n = 318), GV2 (16.2 %–25.3 %, n = 388), and GV3 (>25.3 %, n = 385). According to the Kaplan-Meier curves, the 28-day prognosis was significantly better in GV1 patients than in GV3 [220 (69.2 %) vs. 234 (60.8 %), P = 0.044], and the same was true in the Non-DM subgroup [188 (73.7 %) vs. 108 (61.4 %), P = 0.016]. In a multifactorial COX analysis, GV was significantly associated with the risk of 28-day mortality in patients [HR 1.42, 95 % CI 1.10–1.60, P = 0.012]. In the subgroup analyses, the risk of death was highest in the DM subgroup of patients with GV3 (HR: 1.53, p = 0.003).
Conclusion
GV significantly increases the 28-day risk of death in patients with CS, especially in DM patients. Future optimisation of glucose monitoring techniques and exploration of GV modulation strategies are needed to improve patient prognosis.
What is known about this research topic:
Glycaemic variability (GV) significantly increases the 28-day risk of death in patients with cardiogenic shock (CS).
GV level (16.2 %–25.3 %) was an independent risk factor for 28-day mortality in patients with DM and CS, and GV (>25.3 %) was an independent risk factor for 28-day mortality in Non-DM patients with CS.
What this study adds and its future implications:
More optimal glucose monitoring techniques and GV modulation strategies need to be refined to improve patient outcomes.
血糖变异性（GV）可能反映血糖的急剧上升和急性波动，这与不良心血管事件有关。本研究的目的是探讨GV对合并或不合并糖尿病（DM）的心源性休克（CS）患者28天预后的影响。方法：本回顾性队列研究遵循RECORD（使用观察性常规收集数据进行的研究报告）指南。我们使用重症监护医学信息市场IV （MIMIC-IV）数据库中的临床数据。采用血糖水平变异系数评价GV，根据GV分位数（GV1、GV2和GV3）将患者分为3组，以28天预后为主要指标，机械通气状态、住院时间和ICU住院时间为次要指标，进行统计学分析。结果从MIMIC-IV数据库中共纳入1091例CS患者，其中男性409例（37.49%），女性682例（62.51%）。根据GV水平分为GV1组（< 16.2%, n = 318）、GV2组（16.2% - 25.3%,n = 388）、GV3组（> 25.3%, n = 385）。Kaplan-Meier曲线显示，GV1患者28天预后明显好于GV3患者[220（69.2%）比234 (60.8%),P = 0.044]，非dm亚组亦如此[188（73.7%）比108 (61.4%),P = 0.016]。在多因素COX分析中，GV与患者28天死亡风险显著相关[HR 1.42, 95% CI 1.10-1.60, P = 0.012]。在亚组分析中，GV3患者的DM亚组死亡风险最高（HR: 1.53, p = 0.003）。结论：v显著增加CS患者28天死亡风险，尤其是DM患者。未来需要优化血糖监测技术和探索GV调节策略来改善患者预后。关于本研究主题的已知信息：血糖变异性（GV）显著增加心源性休克（CS）患者28天死亡风险。GV水平（16.2% - 25.3%）是糖尿病合并CS患者28天死亡率的独立危险因素，GV （> 25.3%）是非糖尿病合并CS患者28天死亡率的独立危险因素。本研究补充的内容及其未来意义：需要改进更优的葡萄糖监测技术和GV调节策略，以改善患者的预后。
{"title":"The impact of glycemic variability on the 28-day prognosis of patients with cardiogenic shock with or without diabetes mellitus: A retrospective cohort study","authors":"Jing Tian , Chenming Zhao, Yulu Li, Yi Han","doi":"10.1016/j.jdiacomp.2025.109151","DOIUrl":"10.1016/j.jdiacomp.2025.109151","url":null,"abstract":"<div><div>Glycaemic variability (GV) may reflect sharp rises and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. The aim of this study was to investigate the effect of GV on 28-day outcome in patients with cardiogenic shock (CS) with or without diabetes mellitus (DM).</div></div><div><h3>Methods</h3><div>This retrospective cohort study adhered to the RECORD (REporting of studies Conducted using Observational Routinely-collected Data) guidelines. We used clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. GV was assessed using the coefficient of variation of blood glucose levels and statistically analysed by dividing patients into three groups according to GV tertiles (GV1, GV2 and GV3), with a primary outcome of 28-day prognosis and secondary outcomes of mechanical ventilation status, length of hospital stay and length of ICU stay.</div></div><div><h3>Results</h3><div>A total of 1091 patients from the MIMIC-IV database with CS were included, of which a total of 409 (37.49 %) were male patients and 682 (62.51 %) were female patients. Based on GV levels, three groups were classified as GV1 (<16.2 %, <em>n</em> = 318), GV2 (16.2 %–25.3 %, <em>n</em> = 388), and GV3 (>25.3 %, <em>n</em> = 385). According to the Kaplan-Meier curves, the 28-day prognosis was significantly better in GV1 patients than in GV3 [220 (69.2 %) vs. 234 (60.8 %), <em>P</em> = 0.044], and the same was true in the Non-DM subgroup [188 (73.7 %) vs. 108 (61.4 %), <em>P</em> = 0.016]. In a multifactorial COX analysis, GV was significantly associated with the risk of 28-day mortality in patients [HR 1.42, 95 % CI 1.10–1.60, <em>P</em> = 0.012]. In the subgroup analyses, the risk of death was highest in the DM subgroup of patients with GV3 (HR: 1.53, <em>p</em> = 0.003).</div></div><div><h3>Conclusion</h3><div>GV significantly increases the 28-day risk of death in patients with CS, especially in DM patients. Future optimisation of glucose monitoring techniques and exploration of GV modulation strategies are needed to improve patient prognosis.</div><div><strong>What is known about this research topic:</strong></div><div>Glycaemic variability (GV) significantly increases the 28-day risk of death in patients with cardiogenic shock (CS).</div><div>GV level (16.2 %–25.3 %) was an independent risk factor for 28-day mortality in patients with DM and CS, and GV (>25.3 %) was an independent risk factor for 28-day mortality in Non-DM patients with CS.</div><div><strong>What this study adds and its future implications:</strong></div><div>More optimal glucose monitoring techniques and GV modulation strategies need to be refined to improve patient outcomes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109151"},"PeriodicalIF":3.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861139","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}
This study aimed to evaluate whether a pericardial fat pad (PFP) detected on chest X-ray can estimate metabolic dysfunction-associated steatotic liver disease (MASLD) and visceral fat accumulation.
Methods
Sixty-six patients with type 2 diabetes were categorized on the basis of the presence (n = 40) or absence (n = 26) of PFP on chest X-ray. The visceral fat area (VFA) and visceral-to-subcutaneous fat area ratio (V/S) at the umbilical level were assessed using abdominal computed tomography, whereas the controlled attenuation parameter (CAP) was measured using FibroScan. The fatty liver index (FLI) was estimated using clinical parameters, including body mass index (BMI), blood pressure, and biochemical markers.
Results
Subjects with PFP had a significantly higher BMI and a higher proportion of males. Subjects with PFP demonstrated significantly higher CAP, FLI, VFA, and V/S than those without PFP (P = 0.018, 0.005, < 0.001, and 0.020, respectively). The cutoff values for detecting PFP on chest X-ray were CAP ≥265.5 dB/m, FLI ≥ 30.6, VFA ≥ 118.7 cm2, and V/S ≥ 0.71.
Conclusions
In patients with type 2 diabetes, PFP detected on chest X-ray may serve as an indicator of MASLD and visceral fat accumulation.
{"title":"Pericardial fat pad detected on chest X-ray is closely associated with metabolic dysfunction-associated steatotic liver disease and visceral fat accumulation in patients with type 2 diabetes","authors":"Kentaro Watanabe, Hidenori Nishioka, Masahiro Takubo, Minami Kosuda, Takeshi Yamamotoya, Taro Saigusa, Hisamitsu Ishihara","doi":"10.1016/j.jdiacomp.2025.109150","DOIUrl":"10.1016/j.jdiacomp.2025.109150","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to evaluate whether a pericardial fat pad (PFP) detected on chest X-ray can estimate metabolic dysfunction-associated steatotic liver disease (MASLD) and visceral fat accumulation.</div></div><div><h3>Methods</h3><div>Sixty-six patients with type 2 diabetes were categorized on the basis of the presence (<em>n</em> = 40) or absence (<em>n</em> = 26) of PFP on chest X-ray. The visceral fat area (VFA) and visceral-to-subcutaneous fat area ratio (V/S) at the umbilical level were assessed using abdominal computed tomography, whereas the controlled attenuation parameter (CAP) was measured using FibroScan. The fatty liver index (FLI) was estimated using clinical parameters, including body mass index (BMI), blood pressure, and biochemical markers.</div></div><div><h3>Results</h3><div>Subjects with PFP had a significantly higher BMI and a higher proportion of males. Subjects with PFP demonstrated significantly higher CAP, FLI, VFA, and V/S than those without PFP (<em>P</em> = 0.018, 0.005, < 0.001, and 0.020, respectively). The cutoff values for detecting PFP on chest X-ray were CAP ≥265.5 dB/m, FLI ≥ 30.6, VFA ≥ 118.7 cm<sup>2</sup>, and V/S ≥ 0.71.</div></div><div><h3>Conclusions</h3><div>In patients with type 2 diabetes, PFP detected on chest X-ray may serve as an indicator of MASLD and visceral fat accumulation.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109150"},"PeriodicalIF":3.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879591","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 : 2025-08-08DOI: 10.1016/j.jdiacomp.2025.109149
Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan
Background
Keratoconjunctivitis sicca, or the dry eye disease (DED) is prevalent multifactorial disorder of the tears and ocular surface, which has lately been interested scholars, particularly in establishing its link with diabetes mellitus (DM). This study aimed to evaluate the association between DM and DED through a comprehensive systematic review and meta-analysis of existing published articles, and thus understand the attributed risks for DED development in diabetic patients.
Methods
Four databases, PubMed, Cochrane Library (CENTRAL), Web of Science, and Google Scholar, were electronically searched for relevant publications. Peer-reviewed articles in English language reporting on DED prevalence among diabetic population published over the last 10 years were considered. A random effect model with odds ratio (OR) and risk ratio (RR) and respective confidence intervals were used in our statistical analysis to determine pooled effect sizes.
Results
This study included 23 studies with 5566 participants. Diabetic individuals had a significantly higher prevalence of dry eye disease (DED) than non-diabetics (OR: 2.30 [95 % CI: 1.54–3.43]; RR: 1.69 [95 % CI: 1.28–2.25]). Older age (>50 years), longer diabetes duration (>10 years), and poor glycemic control (HbA1c >7 %) were associated with increased DED risk. Gender-based findings varied, with slightly higher odds in males, though not statistically significant. High heterogeneity (I2 = 72 %) was observed, but sensitivity analyses confirmed result stability. Minimal publication bias was detected. Mechanisms linking diabetes to DED included oxidative stress, inflammation, and neuropathy-related tear dysfunction.
Conclusions
Our study confirmed a significant association between DM and DED prevalence and severity, and diabetic patients exhibit higher DED risks. These risks are pronounced in older adults, particularly those diagnosed with T2DM.”. Hence, early detection and management of DED in diabetic population is a priority to enhance patient's quality of life.
{"title":"Is there a link between dry eye disease and diabetes mellitus? A systematic review and meta-analysis","authors":"Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan","doi":"10.1016/j.jdiacomp.2025.109149","DOIUrl":"10.1016/j.jdiacomp.2025.109149","url":null,"abstract":"<div><h3>Background</h3><div>Keratoconjunctivitis sicca, or the dry eye disease (DED) is prevalent multifactorial disorder of the tears and ocular surface, which has lately been interested scholars, particularly in establishing its link with diabetes mellitus (DM). This study aimed to evaluate the association between DM and DED through a comprehensive systematic review and meta-analysis of existing published articles, and thus understand the attributed risks for DED development in diabetic patients.</div></div><div><h3>Methods</h3><div>Four databases, PubMed, Cochrane Library (CENTRAL), Web of Science, and Google Scholar, were electronically searched for relevant publications. Peer-reviewed articles in English language reporting on DED prevalence among diabetic population published over the last 10 years were considered. A random effect model with odds ratio (OR) and risk ratio (RR) and respective confidence intervals were used in our statistical analysis to determine pooled effect sizes.</div></div><div><h3>Results</h3><div>This study included 23 studies with 5566 participants. Diabetic individuals had a significantly higher prevalence of dry eye disease (DED) than non-diabetics (OR: 2.30 [95 % CI: 1.54–3.43]; RR: 1.69 [95 % CI: 1.28–2.25]). Older age (>50 years), longer diabetes duration (>10 years), and poor glycemic control (HbA1c >7 %) were associated with increased DED risk. Gender-based findings varied, with slightly higher odds in males, though not statistically significant. High heterogeneity (I<sup>2</sup> = 72 %) was observed, but sensitivity analyses confirmed result stability. Minimal publication bias was detected. Mechanisms linking diabetes to DED included oxidative stress, inflammation, and neuropathy-related tear dysfunction.</div></div><div><h3>Conclusions</h3><div>Our study confirmed a significant association between DM and DED prevalence and severity, and diabetic patients exhibit higher DED risks. These risks are pronounced in older adults, particularly those diagnosed with T2DM.”. Hence, early detection and management of DED in diabetic population is a priority to enhance patient's quality of life.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109149"},"PeriodicalIF":3.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863836","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 : 2025-08-05DOI: 10.1016/j.jdiacomp.2025.109148
Emir Muzurović , Ksenija Zečević , Viviana Maggio , Mohamed El Tanani , Manfredi Rizzo
{"title":"Semaglutide and the retina: Weighing evidence against concern","authors":"Emir Muzurović , Ksenija Zečević , Viviana Maggio , Mohamed El Tanani , Manfredi Rizzo","doi":"10.1016/j.jdiacomp.2025.109148","DOIUrl":"10.1016/j.jdiacomp.2025.109148","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 11","pages":"Article 109148"},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794659","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}
Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined systemic condition linking cardiovascular disease, chronic kidney disease and metabolic disorders including type 2 diabetes (T2D). Although the CKM staging has been proposed for integrated risk assessment, its association with all-cause mortality in patients with T2D remains unclear. We investigated the prognosis in patients with T2D assigned by the CKM health stage.
Methods
A total of 632 Japanese patients with T2D were enrolled. The primary endpoint was all-cause death.
Results
The numbers of the recruited patients with stages 2, 3 and 4 were 353 (55.9 %), 116 (18.3 %) and 163 (25.8 %), respectively. During a median follow-up of 64 months (35,327 person-months), 62 patients (9.8 %) died. Kaplan-Meier survival curves analysis showed significant differences in cumulative mortality among CKM health stages (log-rank test: P < 0.001) with higher cumulative mortality in stages 3 and 4 than in stage 2. Multivariable Cox proportional hazard models after adjustment of age, sex, body mass index, current smoking habit, cancer, relevant medications and hemoglobin A1c showed that adjusted hazard ratios (HRs) [95 % confidence intervals] for all-cause death were significantly higher in patients with stages 3 (2.25[1.08–4.69]) and those with stage 4 (2.87[1.41–5.84]) than in those with stage 2 as the reference. After additional adjustment of N-terminal pro-brain natriuretic peptide and estimated glomerular filtration rate among definition criteria for staging, the association of stages with all-cause death remained statistically significant in only stage 4 (2.16[1.02–4.56]).
Conclusion
The CKM health staging is useful for predicting all-cause mortality in Japanese patients with T2D.
{"title":"The health stage of cardiovascular-kidney-metabolic (CKM) syndrome is useful for predicting all-cause mortality in patients with type 2 diabetes: a cohort study in a period prior to the standard use of recent pharmacotherapy","authors":"Keitaro Nishizawa , Marenao Tanaka , Tatsuya Sato , Tomohito Gohda , Nozomu Kamei , Maki Murakoshi , Yukinori Akiyama , Wataru Kawaharata , Hiroki Aida , Hidemichi Kouzu , Naoya Yama , Mitsunobu Kubota , Michiyoshi Sanuki , Yusuke Suzuki , Masato Furuhashi","doi":"10.1016/j.jdiacomp.2025.109146","DOIUrl":"10.1016/j.jdiacomp.2025.109146","url":null,"abstract":"<div><h3>Aim</h3><div>Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined systemic condition linking cardiovascular disease, chronic kidney disease and metabolic disorders including type 2 diabetes (T2D). Although the CKM staging has been proposed for integrated risk assessment, its association with all-cause mortality in patients with T2D remains unclear. We investigated the prognosis in patients with T2D assigned by the CKM health stage.</div></div><div><h3>Methods</h3><div>A total of 632 Japanese patients with T2D were enrolled. The primary endpoint was all-cause death.</div></div><div><h3>Results</h3><div>The numbers of the recruited patients with stages 2, 3 and 4 were 353 (55.9 %), 116 (18.3 %) and 163 (25.8 %), respectively. During a median follow-up of 64 months (35,327 person-months), 62 patients (9.8 %) died. Kaplan-Meier survival curves analysis showed significant differences in cumulative mortality among CKM health stages (log-rank test: <em>P</em> < 0.001) with higher cumulative mortality in stages 3 and 4 than in stage 2. Multivariable Cox proportional hazard models after adjustment of age, sex, body mass index, current smoking habit, cancer, relevant medications and hemoglobin A1c showed that adjusted hazard ratios (HRs) [95 % confidence intervals] for all-cause death were significantly higher in patients with stages 3 (2.25[1.08–4.69]) and those with stage 4 (2.87[1.41–5.84]) than in those with stage 2 as the reference. After additional adjustment of N-terminal pro-brain natriuretic peptide and estimated glomerular filtration rate among definition criteria for staging, the association of stages with all-cause death remained statistically significant in only stage 4 (2.16[1.02–4.56]).</div></div><div><h3>Conclusion</h3><div>The CKM health staging is useful for predicting all-cause mortality in Japanese patients with T2D.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109146"},"PeriodicalIF":3.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781480","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 : 2025-07-30DOI: 10.1016/j.jdiacomp.2025.109144
Michael Fralick , Mats C. Højbjerg Lassen , Jagadish Rangrej , Sahar Asgari , Saad Rais , Michael P. Hillmer , Jamie Lee Fritz , Katarina Zorcic , Bruce A. Perkins , Michael Colacci , Tor Biering-Sørensen , Muhammad Mamdani , Kieran R. Campbell
Background
Sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a small-magnitude but higher risk of diabetic ketoacidosis (DKA). However, objectively identifying patients at lowest and highest risk of DKA is challenging.
Methods
We developed a prediction model using outpatient prescription data from Ontario, Canada and externally validated it using data from Denmark. We included adults with type 2 diabetes mellitus who were newly prescribed an SGLT2i. Our candidate predictors in the model were based on prior work and included the following: Sex, insulin use, prior DKA, dementia, hemoglobin A1C, and creatinine. Our outcome was 1-year risk of hospitalization with DKA. We calculated a risk score using an adaptation of penalized regression for each patient reported test characteristics in Ontario (derivation cohort) and Denmark (external validation cohort).
Results
We identified 322,135 in Ontario and 43,377 adults in Denmark who had type 2 diabetes mellitus and received an SGLT2i. The absolute risk of DKA within 1-year was 0.28 % (N = 916) in Ontario and 0.23 % (N = 101) in Denmark. Using data from Ontario, the risk score for each variable were as follows: Insulin use = 4 points, A1C > 9 % = 4 points and prior DKA = 19 points. All other variables received zero points. The overall model AUC was 63 % in Ontario and 66 % in Denmark (external validation set). Within Ontario, at a score threshold of zero, the risk of DKA was 0.19 % and the PPV was 0.3 % and the sensitivity was 100 % and similar results were observed in Denmark. For adults with a score of 19 or higher, the risk of DKA was 35-fold higher but false positives were common yielding a PPV of 6.7 % and sensitivity was lower at 3 %. In Denmark, adults with a score of 19 or higher had a risk of 11 % and the PPV was 10.2 % and sensitivity was 5 %.
Conclusion
Adults with a score of 0 (that is, simply a lack of DKA history, lack of insulin therapy, and A1c < 9 %) can be reassured that 99.8 % will not experience DKA in the subsequent year. In contrast, for adults with a score of 19 or higher the one-year risk of DKA is approximately 9 %, but false positives and false negatives are common and thus more work is needed to improve the predictive performance of the model.
{"title":"Predicting the occurrence of DKA following sodium glucose co-transporter-2 inhibitors: An international cohort study","authors":"Michael Fralick , Mats C. Højbjerg Lassen , Jagadish Rangrej , Sahar Asgari , Saad Rais , Michael P. Hillmer , Jamie Lee Fritz , Katarina Zorcic , Bruce A. Perkins , Michael Colacci , Tor Biering-Sørensen , Muhammad Mamdani , Kieran R. Campbell","doi":"10.1016/j.jdiacomp.2025.109144","DOIUrl":"10.1016/j.jdiacomp.2025.109144","url":null,"abstract":"<div><h3>Background</h3><div>Sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a small-magnitude but higher risk of diabetic ketoacidosis (DKA). However, objectively identifying patients at lowest and highest risk of DKA is challenging.</div></div><div><h3>Methods</h3><div>We developed a prediction model using outpatient prescription data from Ontario, Canada and externally validated it using data from Denmark. We included adults with type 2 diabetes mellitus who were newly prescribed an SGLT2i. Our candidate predictors in the model were based on prior work and included the following: Sex, insulin use, prior DKA, dementia, hemoglobin A1C, and creatinine. Our outcome was 1-year risk of hospitalization with DKA. We calculated a risk score using an adaptation of penalized regression for each patient reported test characteristics in Ontario (derivation cohort) and Denmark (external validation cohort).</div></div><div><h3>Results</h3><div>We identified 322,135 in Ontario and 43,377 adults in Denmark who had type 2 diabetes mellitus and received an SGLT2i. The absolute risk of DKA within 1-year was 0.28 % (N = 916) in Ontario and 0.23 % (N = 101) in Denmark. Using data from Ontario, the risk score for each variable were as follows: Insulin use = 4 points, A1C > 9 % = 4 points and prior DKA = 19 points. All other variables received zero points. The overall model AUC was 63 % in Ontario and 66 % in Denmark (external validation set). Within Ontario, at a score threshold of zero, the risk of DKA was 0.19 % and the PPV was 0.3 % and the sensitivity was 100 % and similar results were observed in Denmark. For adults with a score of 19 or higher, the risk of DKA was 35-fold higher but false positives were common yielding a PPV of 6.7 % and sensitivity was lower at 3 %. In Denmark, adults with a score of 19 or higher had a risk of 11 % and the PPV was 10.2 % and sensitivity was 5 %.</div></div><div><h3>Conclusion</h3><div>Adults with a score of 0 (that is, simply a lack of DKA history, lack of insulin therapy, and A1c < 9 %) can be reassured that 99.8 % will not experience DKA in the subsequent year. In contrast, for adults with a score of 19 or higher the one-year risk of DKA is approximately 9 %, but false positives and false negatives are common and thus more work is needed to improve the predictive performance of the model.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109144"},"PeriodicalIF":3.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772881","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}
The diabetes medication imeglimin, which operates through a novel mechanism of action and resistance training (RT), a significant exercise therapy, effectively enhances mitochondrial function in skeletal muscles and regulates blood glucose levels. However, the efficacy of the combination therapy remains unclear.
The combination of imeglimin and RT enhanced mitochondrial function, reduced inflammatory cytokine levels, and upregulated the expression of anti-inflammatory and antioxidant-related genes as determined by RT-PCR. Additionally, there was an increase in the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α), a crucial regulator of mitochondrial biogenesis and glucose metabolism. This was accompanied by elevated levels of sirtuins (Sirt) 1 and 3, which positively regulate PGC1-α activity, as well as an increase in nicotinamide adenine dinucleotide (NAD+) levels, which are involved in Sirt1 and Sirt3 activity. Furthermore, an increase in the phosphorylation rate of protein kinase B (Akt), which plays a role in insulin signaling, and upregulation of glucose transporter type 4 (GLUT4), which is involved in glucose uptake, were observed.
These findings suggest that the combination of imeglimin and RT is a promising therapeutic approach to enhance mitochondrial function and glucose metabolic capacity.
{"title":"Combination of imeglimin and resistance exercise improves mitochondrial function and glucose metabolism in skeletal muscles","authors":"Hajime Ishiguro , Keitaro Minato , Keiya Iwaasa , Sijia Wu , Guo Antao , Takumu Tsuchida , Tatsuya Suwabe , Takayuki Katagiri , Hiroshi Suzuki , Masayoshi Masuko , Ken-ichi Watanabe , Takashi Ushiki , Hirohito Sone","doi":"10.1016/j.jdiacomp.2025.109145","DOIUrl":"10.1016/j.jdiacomp.2025.109145","url":null,"abstract":"<div><div>The diabetes medication imeglimin, which operates through a novel mechanism of action and resistance training (RT), a significant exercise therapy, effectively enhances mitochondrial function in skeletal muscles and regulates blood glucose levels. However, the efficacy of the combination therapy remains unclear.</div><div>The combination of imeglimin and RT enhanced mitochondrial function, reduced inflammatory cytokine levels, and upregulated the expression of anti-inflammatory and antioxidant-related genes as determined by RT-PCR. Additionally, there was an increase in the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α), a crucial regulator of mitochondrial biogenesis and glucose metabolism. This was accompanied by elevated levels of sirtuins (Sirt) 1 and 3, which positively regulate PGC1-α activity, as well as an increase in nicotinamide adenine dinucleotide (NAD<sup>+</sup>) levels, which are involved in Sirt1 and Sirt3 activity. Furthermore, an increase in the phosphorylation rate of protein kinase B (Akt), which plays a role in insulin signaling, and upregulation of glucose transporter type 4 (GLUT4), which is involved in glucose uptake, were observed.</div><div>These findings suggest that the combination of imeglimin and RT is a promising therapeutic approach to enhance mitochondrial function and glucose metabolic capacity.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109145"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738471","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 : 2025-07-26DOI: 10.1016/j.jdiacomp.2025.109142
Bruno Bombaci , Stefano Passanisi , Alessandro Longo , Sara Aramnejad , Federica Rigano , Maria Cristina Marzà , Tania Formica , Maria Pecoraro , Fortunato Lombardo , Giuseppina Salzano
Aims
This study aims to explore the relationships between glucose control, psychological well-being, and diabetes-related distress in a population of adolescents with T1D.
Methods
We conducted a cross-sectional study on adolescents with T1D attending a Pediatric Diabetes Unit. Demographic, clinical, and glycemic data were collected, including continuous glucose monitoring (CGM) metrics. Psychological well-being was assessed using the PERMA-Profiler, while diabetes-related distress was measured using the Problem Areas in Diabetes-Teen Version (PAID-T) questionnaire.
Results
Among 133 enrolled adolescents, those with HbA1c ≤ 7 % exhibited significantly higher well-being scores (p = 0.007) and lower distress scores (p = 0.035). Higher time in range was positively associated with well-being (p = 0.002), while glycemic variability negatively impacted psychological outcomes (p = 0.023). Female sex (p = 0.021), longer disease duration (p = 0.022), and the absence of insulin pump therapy (p = 0.032) were significantly associated to higher diabetes-related distress.
Conclusions
Glycemic control is closely related to psychological well-being of adolescents living with T1D. The adoption of diabetes technologies may play a crucial role in reducing diabetes-related distress. Future longitudinal studies should investigate the impact of psychological interventions on CGM outcomes and overall quality of life in adolescents with T1D.
{"title":"The interplay between psychological well-being, diabetes-related distress, and glycemic control: A continuous glucose monitoring analysis from a population of adolescents with type 1 diabetes","authors":"Bruno Bombaci , Stefano Passanisi , Alessandro Longo , Sara Aramnejad , Federica Rigano , Maria Cristina Marzà , Tania Formica , Maria Pecoraro , Fortunato Lombardo , Giuseppina Salzano","doi":"10.1016/j.jdiacomp.2025.109142","DOIUrl":"10.1016/j.jdiacomp.2025.109142","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to explore the relationships between glucose control, psychological well-being, and diabetes-related distress in a population of adolescents with T1D.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study on adolescents with T1D attending a Pediatric Diabetes Unit. Demographic, clinical, and glycemic data were collected, including continuous glucose monitoring (CGM) metrics. Psychological well-being was assessed using the PERMA-Profiler, while diabetes-related distress was measured using the Problem Areas in Diabetes-Teen Version (PAID-T) questionnaire.</div></div><div><h3>Results</h3><div>Among 133 enrolled adolescents, those with HbA1c ≤ 7 % exhibited significantly higher well-being scores (<em>p</em> = 0.007) and lower distress scores (<em>p</em> = 0.035). Higher time in range was positively associated with well-being (<em>p</em> = 0.002), while glycemic variability negatively impacted psychological outcomes (<em>p</em> = 0.023). Female sex (<em>p</em> = 0.021), longer disease duration (<em>p</em> = 0.022), and the absence of insulin pump therapy (<em>p</em> = 0.032) were significantly associated to higher diabetes-related distress.</div></div><div><h3>Conclusions</h3><div>Glycemic control is closely related to psychological well-being of adolescents living with T1D. The adoption of diabetes technologies may play a crucial role in reducing diabetes-related distress. Future longitudinal studies should investigate the impact of psychological interventions on CGM outcomes and overall quality of life in adolescents with T1D.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109142"},"PeriodicalIF":3.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738469","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 : 2025-07-25DOI: 10.1016/j.jdiacomp.2025.109139
Francesco Sacchini , Stefano Mancin , Giovanni Cangelosi , Sara Morales Palomares , Gabriele Caggianelli , Francesco Gravante , Fabio Petrelli
Background/objectives
Diabetic retinopathy (DR) is one of the leading causes of blindness in adults worldwide and represents a critical complication in both type 1 (T1D) and type 2 (T2D) diabetes. Artificial Intelligence (AI) offers a promising opportunity to enhance both the accuracy of screening and the efficiency of ongoing care management, assisting healthcare providers in mitigating the incidence and complications of DR.
Methods
Systematic review of the literature was conducted following PRISMA guidelines. Searches were performed using PubMed-Medline, Scopus, and Embase databases, with the protocol registered on the Open Science Framework (OSF) database: (doi.org/10.17605/OSF.IO/TJ9UH). A predefined search strategy utilizing Boolean operators was applied, and two researchers independently selected articles, with a third resolving any discrepancies.
Results
Of the 2127 articles identified, 8 studies were included. The results highlighted that AI is particularly effective in enhancing the DR screening process in patients with T1D, offering rapid and reliable analysis. Healthcare providers reported positive feedback, noting its significant contribution to improving patient management.
Conclusions
The integration of AI into DR care pathways shows substantial potential for improving early diagnosis and disease management, particularly for patients with T1D. Further research is required to optimize AI implementation and ensure its positive and sustainable impact on public health.
{"title":"The role of artificial intelligence in diabetic retinopathy screening in type 1 diabetes: A systematic review","authors":"Francesco Sacchini , Stefano Mancin , Giovanni Cangelosi , Sara Morales Palomares , Gabriele Caggianelli , Francesco Gravante , Fabio Petrelli","doi":"10.1016/j.jdiacomp.2025.109139","DOIUrl":"10.1016/j.jdiacomp.2025.109139","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Diabetic retinopathy (DR) is one of the leading causes of blindness in adults worldwide and represents a critical complication in both type 1 (T1D) and type 2 (T2D) diabetes. Artificial Intelligence (AI) offers a promising opportunity to enhance both the accuracy of screening and the efficiency of ongoing care management, assisting healthcare providers in mitigating the incidence and complications of DR.</div></div><div><h3>Methods</h3><div>Systematic review of the literature was conducted following PRISMA guidelines. Searches were performed using PubMed-Medline, Scopus, and Embase databases, with the protocol registered on the Open Science Framework (OSF) database: (<span><span>doi.org/10.17605/OSF.IO/TJ9UH</span><svg><path></path></svg></span>). A predefined search strategy utilizing Boolean operators was applied, and two researchers independently selected articles, with a third resolving any discrepancies.</div></div><div><h3>Results</h3><div>Of the 2127 articles identified, 8 studies were included. The results highlighted that AI is particularly effective in enhancing the DR screening process in patients with T1D, offering rapid and reliable analysis. Healthcare providers reported positive feedback, noting its significant contribution to improving patient management.</div></div><div><h3>Conclusions</h3><div>The integration of AI into DR care pathways shows substantial potential for improving early diagnosis and disease management, particularly for patients with T1D. Further research is required to optimize AI implementation and ensure its positive and sustainable impact on public health.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109139"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773160","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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