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":"2025-10-01","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 : 2025-10-01Epub Date: 2025-07-25DOI: 10.1016/j.jdiacomp.2025.109141
Jonathan M. Baier , Kristian L. Funck , Liv Vernstrøm , Søren Gullaksen , Per L. Poulsen , Esben Laugesen
Background
Patients with type 2 diabetes face an increased risk of cardiovascular disease (CVD), partly due to a prothrombotic state with increased platelet reactivity. Colchicine, an anti-inflammatory drug, has shown promise in reducing cardiovascular events, but its effects on platelet function remain unclear. This trial evaluated the effect of low-dose colchicine on platelet aggregation and platelet activation indices in patients with type 2 diabetes.
Methods
In this double-blind, randomized, placebo-controlled trial, 100 participants with type 2 diabetes and previous CVD or a least one cardiovascular risk factor were randomized in a 1:1 ratio to receive either colchicine (0.5 mg/day) or placebo for 26 weeks. Platelet aggregation was assessed using multiple electrode aggregometry expressed as aggregation units (AU) × minutes (mins). Adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin-receptor-activating peptide (TRAP) were used as agonists.
Results
A total of 95 participants completed the trial. After 26 weeks, no significant differences were observed between the colchicine and placebo groups in platelet aggregation induced by ADP (ΔADP-aggregation: 49, 95 % CI: −15;113 AU x mins, p = 0.08), AA (ΔAA-aggregation: −4, 95 % CI: −24;16 %, p = 0.69), or TRAP (ΔTRAP-aggregation: −3, 95 % CI: −11;4 %, p = 0.39). Similarly, no between-group differences were found in platelet parameters, including platelet count mean platelet volume, and immature platelet fraction.
Conclusions
Low-dose colchicine did not significantly alter platelet aggregation or platelet activation indices in patients with type 2 diabetes. These findings suggest that colchicine's cardioprotective effects are not mediated through direct effects on platelet function.
背景：2型糖尿病患者患心血管疾病（CVD）的风险增加，部分原因是血小板反应性增高的血栓形成前状态。秋水仙碱是一种抗炎药物，在减少心血管事件方面有希望，但它对血小板功能的影响尚不清楚。本试验评估了低剂量秋水仙碱对2型糖尿病患者血小板聚集和血小板活化指标的影响。方法在这项双盲、随机、安慰剂对照试验中，100名患有2型糖尿病和既往心血管疾病或至少一种心血管危险因素的参与者按1:1的比例随机接受秋水仙碱（0.5 mg/天）或安慰剂治疗26周。血小板聚集用多电极聚集法评估，聚集单位（AU） ×分钟（min）。二磷酸腺苷（ADP）、花生四烯酸（AA）和凝血酶受体激活肽（TRAP）作为激动剂。结果共有95名参与者完成了试验。26周后，在ADP （ΔADP-aggregation: 49, 95% CI:−15;113 AU x min, p = 0.08）、AA （ΔAA-aggregation:−4,95% CI:−24;16%,p = 0.69）或TRAP （ΔTRAP-aggregation:−3,95% CI:−11;4%,p = 0.39）诱导的血小板聚集方面，秋水仙碱组与安慰剂组之间无显著差异。同样，各组间的血小板参数，包括血小板计数、平均血小板体积和未成熟血小板分数均无差异。结论慢剂量秋水仙碱对2型糖尿病患者血小板聚集和血小板活化指标无显著影响。这些发现表明秋水仙碱的心脏保护作用不是通过直接影响血小板功能介导的。临床试验注册信息链接：https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003525-30/DK
{"title":"Effect of colchicine on platelet aggregation in patients with type 2 diabetes: Results from a randomized placebo-controlled trial","authors":"Jonathan M. Baier , Kristian L. Funck , Liv Vernstrøm , Søren Gullaksen , Per L. Poulsen , Esben Laugesen","doi":"10.1016/j.jdiacomp.2025.109141","DOIUrl":"10.1016/j.jdiacomp.2025.109141","url":null,"abstract":"<div><h3>Background</h3><div>Patients with type 2 diabetes face an increased risk of cardiovascular disease (CVD), partly due to a prothrombotic state with increased platelet reactivity. Colchicine, an anti-inflammatory drug, has shown promise in reducing cardiovascular events, but its effects on platelet function remain unclear. This trial evaluated the effect of low-dose colchicine on platelet aggregation and platelet activation indices in patients with type 2 diabetes.</div></div><div><h3>Methods</h3><div>In this double-blind, randomized, placebo-controlled trial, 100 participants with type 2 diabetes and previous CVD or a least one cardiovascular risk factor were randomized in a 1:1 ratio to receive either colchicine (0.5 mg/day) or placebo for 26 weeks. Platelet aggregation was assessed using multiple electrode aggregometry expressed as aggregation units (AU) × minutes (mins). Adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin-receptor-activating peptide (TRAP) were used as agonists.</div></div><div><h3>Results</h3><div>A total of 95 participants completed the trial. After 26 weeks, no significant differences were observed between the colchicine and placebo groups in platelet aggregation induced by ADP (ΔADP-aggregation: 49, 95 % CI: −15;113 AU x mins, <em>p</em> = 0.08), AA (ΔAA-aggregation: −4, 95 % CI: −24;16 %, <em>p</em> = 0.69), or TRAP (ΔTRAP-aggregation: −3, 95 % CI: −11;4 %, <em>p</em> = 0.39). Similarly, no between-group differences were found in platelet parameters, including platelet count mean platelet volume, and immature platelet fraction.</div></div><div><h3>Conclusions</h3><div>Low-dose colchicine did not significantly alter platelet aggregation or platelet activation indices in patients with type 2 diabetes. These findings suggest that colchicine's cardioprotective effects are not mediated through direct effects on platelet function.</div></div><div><h3>Clinical trial registration information</h3><div>EudraCT-no.: 2021-003525-30</div><div>Link: <span><span>https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003525-30/DK</span><svg><path></path></svg></span></div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109141"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704248","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 : 2025-10-01Epub Date: 2025-07-03DOI: 10.1016/j.jdiacomp.2025.109115
Helen Michaela de Oliveira , Mariano Gallo Ruelas , Victor Hugo Palhares Flávio-Reis , Ivo Queiroz , Deivyd Vieira Silva Cavalcante , Lucas Mendes Barbosa , Fernanda Valeriano Zamora
Purpose
To compare the efficacy and safety of next-generation basal insulin efsitora versus insulin degludec in managing type 1 and type 2 diabetes.
Methods
We systematically searched PubMed, Embase, and CENTRAL databases until October 2024. This study followed PRISMA guidelines. Statistical analyses were performed using R version 4.4.1. The risk of bias was assessed using the RoB2 tool, and the quality of evidence was evaluated using the GRADE approach. This study was registered in PROSPERO under protocol CRD42024597806.
Results
Six randomized controlled trials involving 2590 patients were included in the analysis. Of these, 1376 (53.13 %) received efsitora insulin. No significant differences were observed between efsitora and degludec in glycemic efficacy outcomes, including HbA1c reduction, fasting blood glucose, weight change, and proportion of patients achieving HbA1c <7 %. Regarding safety outcomes, most endpoints, such as adverse events, injection site reactions, hypersensitivity, severe hypoglycemia, and mortality, were comparable between groups, with no significant subgroup effects. However, subgroup analysis revealed a lower incidence of nocturnal hypoglycemia with efsitora in patients with type 2 diabetes, and a higher rate of serious adverse events in patients with type 1 diabetes, suggesting potential population-specific differences in safety profiles.
Conclusion
Efsitora and degludec insulins show similar overall efficacy and safety in the management of diabetes. However, subgroup analyses indicate that patient-specific factors, such as diabetes type, may influence the risk of certain adverse events. These findings support the importance of individualized insulin selection based on patient characteristics and risk profiles.
{"title":"Degludec insulin versus efsitora insulin in diabetes mellitus management: A systematic review and meta-analysis","authors":"Helen Michaela de Oliveira , Mariano Gallo Ruelas , Victor Hugo Palhares Flávio-Reis , Ivo Queiroz , Deivyd Vieira Silva Cavalcante , Lucas Mendes Barbosa , Fernanda Valeriano Zamora","doi":"10.1016/j.jdiacomp.2025.109115","DOIUrl":"10.1016/j.jdiacomp.2025.109115","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the efficacy and safety of next-generation basal insulin efsitora versus insulin degludec in managing type 1 and type 2 diabetes.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Embase, and CENTRAL databases until October 2024. This study followed PRISMA guidelines. Statistical analyses were performed using R version 4.4.1. The risk of bias was assessed using the RoB2 tool, and the quality of evidence was evaluated using the GRADE approach. This study was registered in PROSPERO under protocol CRD42024597806.</div></div><div><h3>Results</h3><div>Six randomized controlled trials involving 2590 patients were included in the analysis. Of these, 1376 (53.13 %) received efsitora insulin. No significant differences were observed between efsitora and degludec in glycemic efficacy outcomes, including HbA1c reduction, fasting blood glucose, weight change, and proportion of patients achieving HbA1c <7 %. Regarding safety outcomes, most endpoints, such as adverse events, injection site reactions, hypersensitivity, severe hypoglycemia, and mortality, were comparable between groups, with no significant subgroup effects. However, subgroup analysis revealed a lower incidence of nocturnal hypoglycemia with efsitora in patients with type 2 diabetes, and a higher rate of serious adverse events in patients with type 1 diabetes, suggesting potential population-specific differences in safety profiles.</div></div><div><h3>Conclusion</h3><div>Efsitora and degludec insulins show similar overall efficacy and safety in the management of diabetes. However, subgroup analyses indicate that patient-specific factors, such as diabetes type, may influence the risk of certain adverse events. These findings support the importance of individualized insulin selection based on patient characteristics and risk profiles.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109115"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571010","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 : 2025-10-01Epub Date: 2025-07-10DOI: 10.1016/j.jdiacomp.2025.109135
Harsha A. Dissanayake , Christine A. Kiire , David Preiss , Garry D. Tan
Diabetic retinopathy (DR) is a leading cause of blindness despite advances in treatment and there remains an unmet need for low-cost interventions to prevent and slow the progression of DR. Fenofibrate has shown promise as a useful adjunct in DR management and is licensed for use in the treatment of DR in a few countries. However, the data supporting the use of fenofibrate for the treatment of DR emerged from subsidiary analyses of the FIELD, ACCORD-LIPID and its sub-study ACCORD-EYE trials, which were primarily designed to evaluate cardiovascular outcomes. The recently concluded LENS trial, designed to evaluate the effect of fenofibrate on progression of DR, has shown clear evidence of benefit over medium-term follow-up (i.e., 4–5 years), and confirmed its safety in people with type 1 or type 2 diabetes. These benefits appear to be independent of fenofibrate's lipid lowering effects and are more likely to be mediated via its direct effects on the eye. In this narrative review on the use of fenofibrate in the treatment of DR, we summarise the possible mechanisms of action, existing evidence from randomised trials, and implications for clinical practice and research.
{"title":"The use of fenofibrate in diabetic retinopathy: Narrative review","authors":"Harsha A. Dissanayake , Christine A. Kiire , David Preiss , Garry D. Tan","doi":"10.1016/j.jdiacomp.2025.109135","DOIUrl":"10.1016/j.jdiacomp.2025.109135","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a leading cause of blindness despite advances in treatment and there remains an unmet need for low-cost interventions to prevent and slow the progression of DR. Fenofibrate has shown promise as a useful adjunct in DR management and is licensed for use in the treatment of DR in a few countries. However, the data supporting the use of fenofibrate for the treatment of DR emerged from subsidiary analyses of the FIELD, ACCORD-LIPID and its sub-study ACCORD-EYE trials, which were primarily designed to evaluate cardiovascular outcomes. The recently concluded LENS trial, designed to evaluate the effect of fenofibrate on progression of DR, has shown clear evidence of benefit over medium-term follow-up (i.e., 4–5 years), and confirmed its safety in people with type 1 or type 2 diabetes. These benefits appear to be independent of fenofibrate's lipid lowering effects and are more likely to be mediated via its direct effects on the eye. In this narrative review on the use of fenofibrate in the treatment of DR, we summarise the possible mechanisms of action, existing evidence from randomised trials, and implications for clinical practice and research.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109135"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631797","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 : 2025-10-01Epub Date: 2025-09-06DOI: 10.1016/S1056-8727(25)00220-X
{"title":"Contents/Barcode","authors":"","doi":"10.1016/S1056-8727(25)00220-X","DOIUrl":"10.1016/S1056-8727(25)00220-X","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109167"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007692","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 : 2025-10-01Epub Date: 2025-07-02DOI: 10.1016/j.jdiacomp.2025.109118
Ziyue Zhang , Rongpei Yang , Wen Wu , Zhen Wang
Aims
Patients with diabetes have experienced excess cardiovascular (CV) diseases. Accurate prediction of CV risk has been one of the ultimate tasks of contemporary diabetology. Aortic stiffness (AS), a key indicator of vascular health, has been increasingly considered as a valuable biomarker for CV risk and mortality prediction. We sought to investigate and calculate the predictive value of AS measured by pulse wave velocity (PWV) for cardiovascular CV events and/or all-cause mortality for patients with diabetes.
Methods
A comprehensive search was carried out in the PubMed, Embase, and Cochrane Library up to 11 June 2024. We included observational studies where investigators reported the association of PWV with CV events or all-cause mortality in patients with diabetes. Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Information about study design, participant demographics, baseline characteristics, hazard ratio (HR) and so on were extracted from study documents. Heterogeneity among studies was assessed by using the I2 statistic. Acceptable levels of heterogeneity were defined as I2 < 75 %. Fixed-effects model (Inverse Variance) was utilized for synthesis when I2 < 50 %, and a random-effects model (DerSimonian-Laird) was used when I2 > 50 %. Visual inspection of funnel plots, Egger's test and Begg's test were used to evaluate the existence of publication bias. Trim-and-fill method was further used to identify and adjust for publication bias.
Results
We included 12 studies. For each 1 m/s increase in cfPWV in diabetes population, the risk of a CV events increased by 7 % [HR 1.07, 95%CI 1.02–1.12, 3132 subjects, random-effects model], and the risk of all-cause mortality increased by 7 % [HR 1.07, 95%CI 1.03–1.12, 1700 subjects, fixed-effects model]. Diabetic patients with higher cfPWV had a 1.71-fold increased risk of CV events compared with those with lower cfPWV [HR 1.71, 95%CI 1.22–2.40, 2075 subjects, random-effects model]. Since different studies may have used different modeling methods, we performed a quantitative synthesis for each modeling method separately, which consequently led to variations in subjects sizes.
Conclusions
Despite certain limitations of this study, such as heterogeneity, our findings indicate that PWV could be a strong predictor of future CV events and all-cause mortality in patients with diabetes.
{"title":"Association of aortic pulse wave velocity with cardiovascular outcomes and all-cause mortality in diabetes: A systematic review and meta-analysis","authors":"Ziyue Zhang , Rongpei Yang , Wen Wu , Zhen Wang","doi":"10.1016/j.jdiacomp.2025.109118","DOIUrl":"10.1016/j.jdiacomp.2025.109118","url":null,"abstract":"<div><h3>Aims</h3><div>Patients with diabetes have experienced excess cardiovascular (CV) diseases. Accurate prediction of CV risk has been one of the ultimate tasks of contemporary diabetology. Aortic stiffness (AS), a key indicator of vascular health, has been increasingly considered as a valuable biomarker for CV risk and mortality prediction. We sought to investigate and calculate the predictive value of AS measured by pulse wave velocity (PWV) for cardiovascular CV events and/or all-cause mortality for patients with diabetes.</div></div><div><h3>Methods</h3><div>A comprehensive search was carried out in the PubMed, Embase, and Cochrane Library up to 11 June 2024. We included observational studies where investigators reported the association of PWV with CV events or all-cause mortality in patients with diabetes. Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Information about study design, participant demographics, baseline characteristics, hazard ratio (HR) and so on were extracted from study documents. Heterogeneity among studies was assessed by using the I<sup>2</sup> statistic. Acceptable levels of heterogeneity were defined as I<sup>2</sup> < 75 %. Fixed-effects model (Inverse Variance) was utilized for synthesis when I<sup>2</sup> < 50 %, and a random-effects model (DerSimonian-Laird) was used when I<sup>2</sup> > 50 %. Visual inspection of funnel plots, Egger's test and Begg's test were used to evaluate the existence of publication bias. Trim-and-fill method was further used to identify and adjust for publication bias.</div></div><div><h3>Results</h3><div>We included 12 studies. For each 1 m/s increase in cfPWV in diabetes population, the risk of a CV events increased by 7 % [HR 1.07, 95%CI 1.02–1.12, 3132 subjects, random-effects model], and the risk of all-cause mortality increased by 7 % [HR 1.07, 95%CI 1.03–1.12, 1700 subjects, fixed-effects model]. Diabetic patients with higher cfPWV had a 1.71-fold increased risk of CV events compared with those with lower cfPWV [HR 1.71, 95%CI 1.22–2.40, 2075 subjects, random-effects model]. Since different studies may have used different modeling methods, we performed a quantitative synthesis for each modeling method separately, which consequently led to variations in subjects sizes.</div></div><div><h3>Conclusions</h3><div>Despite certain limitations of this study, such as heterogeneity, our findings indicate that PWV could be a strong predictor of future CV events and all-cause mortality in patients with diabetes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109118"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548694","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 : 2025-10-01Epub Date: 2025-06-30DOI: 10.1016/j.jdiacomp.2025.109116
Kevin Cowart , Christopher Murphy , Nicholas Carris
Aims
To evaluate the association between tirzepatide and the risk of developing erectile dysfunction (ED) in men with type 2 diabetes (T2D), compared with sitagliptin, injectable semaglutide, and dulaglutide.
Methods
This retrospective cohort study used the TriNetX global health research network from May 13, 2022 to May 17, 2025. Male patients aged 18–70 with T2D and no prior ED were included. Three 1:1 propensity score-matched comparisons were conducted: tirzepatide vs. sitagliptin, injectable semaglutide, or dulaglutide. The outcome was a diagnosis of ED or prescription of a PDE-5 inhibitor.
Results
Tirzepatide was associated with a significantly reduced risk of ED across all comparisons. Risk ratios (RR) for the composite outcome of ED diagnosis or PDE-5 inhibitor use were: tirzepatide vs. sitagliptin: RR, 0.70 (95 % CI: 0.64,0.76); tirzepatide vs. injectable semaglutide: RR, 0.67 (95 % CI: 0.62,0.72); tirzepatide vs. dulaglutide: RR, 0.55 (95 % CI: 0.51,0.59). All comparisons were statistically significant (p < 0.001).
Conclusions
Tirzepatide was associated with a lower risk of ED in men with T2D compared to sitagliptin, injectable semaglutide, and dulaglutide. Randomized trials are needed to confirm these findings and explore potential mechanisms.
{"title":"Association of tirzepatide with erectile dysfunction in people with type 2 diabetes","authors":"Kevin Cowart , Christopher Murphy , Nicholas Carris","doi":"10.1016/j.jdiacomp.2025.109116","DOIUrl":"10.1016/j.jdiacomp.2025.109116","url":null,"abstract":"<div><h3>Aims</h3><div>To evaluate the association between tirzepatide and the risk of developing erectile dysfunction (ED) in men with type 2 diabetes (T2D), compared with sitagliptin, injectable semaglutide, and dulaglutide.</div></div><div><h3>Methods</h3><div>This retrospective cohort study used the TriNetX global health research network from May 13, 2022 to May 17, 2025. Male patients aged 18–70 with T2D and no prior ED were included. Three 1:1 propensity score-matched comparisons were conducted: tirzepatide vs. sitagliptin, injectable semaglutide, or dulaglutide. The outcome was a diagnosis of ED or prescription of a PDE-5 inhibitor.</div></div><div><h3>Results</h3><div>Tirzepatide was associated with a significantly reduced risk of ED across all comparisons. Risk ratios (RR) for the composite outcome of ED diagnosis or PDE-5 inhibitor use were: tirzepatide vs. sitagliptin: RR, 0.70 (95 % CI: 0.64,0.76); tirzepatide vs. injectable semaglutide: RR, 0.67 (95 % CI: 0.62,0.72); tirzepatide vs. dulaglutide: RR, 0.55 (95 % CI: 0.51,0.59). All comparisons were statistically significant (<em>p</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Tirzepatide was associated with a lower risk of ED in men with T2D compared to sitagliptin, injectable semaglutide, and dulaglutide. Randomized trials are needed to confirm these findings and explore potential mechanisms.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109116"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548692","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":"2025-10-01","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}
Identify correlates of poor sleep quality among people living with type 1 diabetes (PwT1D).
Methods
Data were extracted from the BETTER Registry. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Sociodemographic characteristics (age, biological sex, education, income, ethnicity, body mass index); diabetes-related (diabetes duration, glucose monitoring method, treatment type, hypoglycemia awareness); psychological (fear of hypoglycemia, diabetes-related distress and stigma, depression, social support); and behavioral (snacking before bedtime, caffeine, alcohol and cannabis use, moderate-to-vigorous physical activity [MVPA]) variables were tested in multivariate logistic regression analyses for their association with poor sleep quality (PSQI >5).
Results
A total of 1322 PwT1D (mean age: 45.0 ± 15.0 years; 66.9 % female) had sleep data. The mean PSQI score was 6.0 ± 3.4 and 47.3 % had poor sleep quality. Being female (OR = 1.422; 95 % CI: 1.080–1.873), with overweight/obesity (OR = 1.376; 95 % CI: 1.067–1.775), greater fear of hypoglycemia (OR = 1.016; 95 % CI: 1.008–1.023), having moderate-to-severe depression (OR = 6.160; 95 % CI: 4.250–8.929), always snacking before bedtime (OR = 1.706; 95 % CI: 1.124–2.590), using cannabis (OR = 1.578; 95 % CI: 1.152–2.161), and accumulating <150 min/week of MVPA (OR = 1.563; 95 % CI: 1.107–2.203) were correlates of poor sleep quality.
Conclusions
Many PwT1D have poor sleep quality, and their sleep is associated with various sociodemographic, psychological, and behavioral factors.
{"title":"BETTER sleep: Sleep quality among adults living with type 1 diabetes in Canada","authors":"Lydi-Anne Vézina-Im , Anne-Frédérique Turcotte , Virginie Messier , Stéphane Turcotte , Ariane Brossard , Jacques Pelletier , Tara Nassar , Rémi Rabasa-Lhoret , Anne-Sophie Brazeau","doi":"10.1016/j.jdiacomp.2025.109137","DOIUrl":"10.1016/j.jdiacomp.2025.109137","url":null,"abstract":"<div><h3>Aims</h3><div>Identify correlates of poor sleep quality among people living with type 1 diabetes (PwT1D).</div></div><div><h3>Methods</h3><div>Data were extracted from the BETTER Registry. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Sociodemographic characteristics (age, biological sex, education, income, ethnicity, body mass index); diabetes-related (diabetes duration, glucose monitoring method, treatment type, hypoglycemia awareness); psychological (fear of hypoglycemia, diabetes-related distress and stigma, depression, social support); and behavioral (snacking before bedtime, caffeine, alcohol and cannabis use, moderate-to-vigorous physical activity [MVPA]) variables were tested in multivariate logistic regression analyses for their association with poor sleep quality (PSQI >5).</div></div><div><h3>Results</h3><div>A total of 1322 PwT1D (mean age: 45.0 ± 15.0 years; 66.9 % female) had sleep data. The mean PSQI score was 6.0 ± 3.4 and 47.3 % had poor sleep quality. Being female (OR = 1.422; 95 % CI: 1.080–1.873), with overweight/obesity (OR = 1.376; 95 % CI: 1.067–1.775), greater fear of hypoglycemia (OR = 1.016; 95 % CI: 1.008–1.023), having moderate-to-severe depression (OR = 6.160; 95 % CI: 4.250–8.929), always snacking before bedtime (OR = 1.706; 95 % CI: 1.124–2.590), using cannabis (OR = 1.578; 95 % CI: 1.152–2.161), and accumulating <150 min/week of MVPA (OR = 1.563; 95 % CI: 1.107–2.203) were correlates of poor sleep quality.</div></div><div><h3>Conclusions</h3><div>Many PwT1D have poor sleep quality, and their sleep is associated with various sociodemographic, psychological, and behavioral factors.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109137"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662638","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 : 2025-10-01Epub 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":"2025-10-01","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}
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