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Long-term mortality rates after lower extremity amputation in individuals with and without diabetes mellitus (DUDE-10): A retrospective matched cohort study
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108956
L. Rosien , H.J.G. Bilo , J. Oskam , D. Ruwaard , R.O.B. Gans , M.A. Edens , M.J. Molegraaf , P.R. van Dijk

Background/objectives

To determine mortality rates after lower extremity amputation (LEA) in individuals with and without diabetes mellitus (DM).

Methods

Retrospective, observational study using data from a database covering >99 % of the Dutch population. LEAs in 2016 were identified, and mortality data from 2016 to 2021 were analyzed. Study group 1 (SG1) included individuals with DM and LEA (DM+/LEA+) with two control groups (CG), DM+/LEA− (matched by age, sex, without (1a) and with (1b) socioeconomic status matching). Study group 2 (SG2) (DM+/LEA+) was composed after matching with non-DM individuals with LEA (DM−/LEA+ (2a)).

Results

Among 5145 individuals with LEA in 2016, 56 % had DM. Five-year mortality was 61.2 % in SG1 (DM+/LEA+) and 27.9 % in CG1a (DM+, LEA−) and 1b. Study group 2 (DM+/LEA+) had a 62.6 % five-year mortality rate, compared to 56.4 % in CG2a (DM−/LEA+).

Conclusions

Mortality after LEA is high, especially in DM; socioeconomic status (SES) does not significantly impact mortality.

Level of evidence

Level III retrospective cohort study.
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引用次数: 0
The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease 西马鲁肽联合二甲双胍对2型糖尿病合并非酒精性脂肪肝患者肝脏炎症和胰腺β细胞功能的影响
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2024.108932
Rong Ren , Yanxia Pei , Lufei Kong , Yixin Shi

Background

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD.

Methods

This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo).

Results

Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59 ± 5.67 U/L in SAM vs. 25.56 ± 5.46 U/L in M; AST: 18.97 ± 3.94 U/L in SAM vs. 20.15 ± 3.95 U/L in M), reduced fibrosis (FIB-4 index: 1.05 ± 0.44 in SAM vs. 1.16 ± 0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18 ± 1.09 in SAM vs. 4.84 ± 1.15 in M; DIo: 0.18 ± 0.06 in SAM vs. 0.16 ± 0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group.

Conclusion

The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone.
背景:2型糖尿病(T2DM)和非酒精性脂肪性肝病(NAFLD)通常是由胰岛素抵抗和全身炎症驱动的共存疾病。迫切需要针对这两种代谢紊乱的有效管理策略。本研究探讨了胰高血糖素样肽-1受体激动剂semaglutide与二甲双胍联合使用对T2DM和NAFLD患者肝脏炎症和胰腺β细胞功能的影响。方法:本回顾性研究分析了2021年1月至2023年12月在我院治疗的261例T2DM和NAFLD患者。将患者分为两组:单独使用二甲双胍127例(M组),semaglutide联合使用二甲双胍134例(SAM组)。采用丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转移酶(γ-GTP)和FIB-4指数评估肝脏炎症和纤维化程度。采用松田指数、糖化血红蛋白(HbA1c)、空腹血糖和口腔处置指数(DIo)评估胰腺β细胞功能和胰岛素敏感性。结果:治疗后,SAM组肝脏炎症指标明显改善(ALT: SAM组23.59±5.67 U/L vs M组25.56±5.46 U/L;AST: SAM为18.97±3.94 U/L, M为20.15±3.95 U/L),纤维化减少(FIB-4指数:SAM为1.05±0.44,M为1.16±0.51),细胞功能增强(Matsuda指数:SAM为5.18±1.09,M为4.84±1.15;SAM组的DIo: 0.18±0.06 vs. M组的DIo: 0.16±0.05),血糖控制(HbA1c降低)也优于SAM组。结论:与单用二甲双胍相比,西马鲁肽联合二甲双胍可显著改善T2DM和NAFLD患者的肝脏炎症、纤维化和β细胞功能。
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引用次数: 0
Comprehensive treatment with dapagliflozin in elderly chronic kidney disease patients: Clinical efficacy and impact on body composition 达格列净综合治疗老年慢性肾病患者的临床疗效及对体成分的影响。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108951
Kazuhiro Nomura , Toshiyuki Takata , Naokazu Muramae , Hiroaki Takahashi , Kozue Abe , Tomokazu Matsuda

Background

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is widely used for treating heart failure and chronic kidney disease (CKD). While its renoprotective effects are well established, concerns remain regarding its impact on muscle mass and function, especially in elderly patients.

Objective

To assess the effects of dapagliflozin on renal function, body composition, and muscle strength in elderly CKD patients.

Methods

Twelve elderly CKD patients (75.6 ± 1.4 years) were treated with dapagliflozin for 12 months. Body composition, serum parameters, and muscle function were evaluated at baseline, 6 months, and 12 months. Measurements included changes in eGFR, liver function, HbA1c, and muscle strength.

Results

Dapagliflozin treatment stabilized eGFR without significant improvement, but proteinuria was notably reduced in most patients, indicating a positive renal effect. AST and ALT levels showed significant reduction after 12 months, suggesting improved liver function. No significant changes were observed in body weight, BMI, or muscle mass. Muscle function, as measured by the 5-sit-to-stand test, improved significantly, while grip strength remained stable. No serious adverse events were reported.

Conclusion

Dapagliflozin is a safe and effective treatment for CKD in elderly patients, demonstrating renal protection and improved liver function without adversely affecting muscle mass or strength. The study supports the use of dapagliflozin as part of a comprehensive approach, combining pharmacotherapy, lifestyle modification, and exercise to optimize patient outcomes in CKD management.
背景:达格列净是一种钠-葡萄糖共转运蛋白2 (SGLT2)抑制剂,广泛用于治疗心力衰竭和慢性肾脏疾病(CKD)。虽然它对肾脏的保护作用已经得到证实,但人们仍然担心它对肌肉质量和功能的影响,尤其是对老年患者。目的:评价达格列净对老年CKD患者肾功能、体成分和肌力的影响。方法:12例老年CKD患者(75.6±1.4岁)应用达格列净治疗12个月。在基线、6个月和12个月时评估体成分、血清参数和肌肉功能。测量包括eGFR、肝功能、糖化血红蛋白和肌肉力量的变化。结果:达格列净治疗后eGFR稳定,无明显改善,但大多数患者蛋白尿明显减少,提示肾作用积极。12个月后AST和ALT水平明显降低,提示肝功能改善。没有观察到体重、BMI或肌肉质量的显著变化。通过5次坐立测试,肌肉功能得到了显著改善,而握力保持稳定。无严重不良事件报告。结论:达格列净是一种安全有效的治疗老年CKD患者的药物,具有保护肾脏和改善肝功能的作用,且不会对肌肉质量或力量产生不良影响。该研究支持将达格列净作为综合治疗方法的一部分,结合药物治疗、生活方式改变和运动来优化CKD治疗的患者结果。
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引用次数: 0
Association between muscle fatigability and diabetic kidney disease complications in patients with type 2 diabetes
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108955
Yuma Hirano , Daisuke Tsuriya , Kenichi Kono , Tomoyuki Fujikura , Tomoya Yamaguchi , Kento Matsushita , Yurina Yokoyama , Katsuya Yamauchi , Yusuke Nishida

Aims

Type 2 diabetes mellitus (T2DM) requires the maintenance of high physical activity levels and specific interventions tailored to the characteristics of each patient. We hypothesized that T2DM combined with diabetic kidney disease (DKD) could increase muscle fatigability, becoming a specific contributor to physical inactivity. This study aimed to determine the association between muscle fatigability and DKD complications and investigate the relationship between muscle fatigability and physical activity in patients with T2DM.

Methods

Overall, 50 patients with T2DM aged 40–65 years and with an estimated glomerular filtration rate of 30 mL/min/1.73 m2 or higher were included. Muscle function was assessed using an isokinetic dynamometer. Muscle fatigability (maximal voluntary concentric contraction [ΔMVCC] velocity, maximal voluntary isometric contraction [ΔMVIC] torque), which indicated the decrease in angular velocity and muscle strength associated with the exercise task, was calculated. The patient characteristics, physical activity (IPAQ-SV), knee extensor strength, and skeletal muscle index were evaluated. Participants were divided into two groups (DKD and non-DKD) according to the presence of DKD, and ΔMVCC velocity and ΔMVIC torque were compared.

Results

ΔMVCC velocity was significantly higher in the DKD group than in the non-DKD group (p < 0.05). Similarly, ΔMVIC torque was significantly higher in the DKD group than in the non-DKD group (p < 0.05). Subgroup analyses showed that ΔMVCC velocity was independently associated with physical activity in the DKD group (odds ratio: 0.93, 95 % confidence interval: 0.88–0.99).

Conclusions

Muscle fatigability increased with DKD in patients with T2DM and might be related to physical activity.
{"title":"Association between muscle fatigability and diabetic kidney disease complications in patients with type 2 diabetes","authors":"Yuma Hirano ,&nbsp;Daisuke Tsuriya ,&nbsp;Kenichi Kono ,&nbsp;Tomoyuki Fujikura ,&nbsp;Tomoya Yamaguchi ,&nbsp;Kento Matsushita ,&nbsp;Yurina Yokoyama ,&nbsp;Katsuya Yamauchi ,&nbsp;Yusuke Nishida","doi":"10.1016/j.jdiacomp.2025.108955","DOIUrl":"10.1016/j.jdiacomp.2025.108955","url":null,"abstract":"<div><h3>Aims</h3><div>Type 2 diabetes mellitus (T2DM) requires the maintenance of high physical activity levels and specific interventions tailored to the characteristics of each patient. We hypothesized that T2DM combined with diabetic kidney disease (DKD) could increase muscle fatigability, becoming a specific contributor to physical inactivity. This study aimed to determine the association between muscle fatigability and DKD complications and investigate the relationship between muscle fatigability and physical activity in patients with T2DM.</div></div><div><h3>Methods</h3><div>Overall, 50 patients with T2DM aged 40–65 years and with an estimated glomerular filtration rate of 30 mL/min/1.73 m<sup>2</sup> or higher were included. Muscle function was assessed using an isokinetic dynamometer. Muscle fatigability (maximal voluntary concentric contraction [ΔMVCC] velocity, maximal voluntary isometric contraction [ΔMVIC] torque), which indicated the decrease in angular velocity and muscle strength associated with the exercise task, was calculated. The patient characteristics, physical activity (IPAQ-SV), knee extensor strength, and skeletal muscle index were evaluated. Participants were divided into two groups (DKD and non-DKD) according to the presence of DKD, and ΔMVCC velocity and ΔMVIC torque were compared.</div></div><div><h3>Results</h3><div>ΔMVCC velocity was significantly higher in the DKD group than in the non-DKD group (<em>p</em> &lt; 0.05). Similarly, ΔMVIC torque was significantly higher in the DKD group than in the non-DKD group (<em>p</em> &lt; 0.05). Subgroup analyses showed that ΔMVCC velocity was independently associated with physical activity in the DKD group (odds ratio: 0.93, 95 % confidence interval: 0.88–0.99).</div></div><div><h3>Conclusions</h3><div>Muscle fatigability increased with DKD in patients with T2DM and might be related to physical activity.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108955"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143129414","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}
引用次数: 0
The association between age at diagnosis of diabetes and development of diabetic retinopathy and assessment of healthcare access as an effect modifier 糖尿病诊断年龄与糖尿病视网膜病变发展之间的关系以及医疗保健可及性评估作为影响调节因子。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2024.108931
Bria L. George , Alejandro M. Perez , Pura Rodriguez , Prashant Parekh , Noël C. Barengo

Aims

To examine if healthcare access modifies the association between age at diagnosis of diabetes and the prevalence of retinopathy.

Methods

BRFSS 2020 survey data was obtained from 12,198 adults. Participants with missing information in the variables “retinopathy” (N = 569) and “insurance-cost barrier” (N = 75) were excluded. The final sample included 11,556 participants. Age at diagnosis of diabetes was the main exposure and retinopathy was the main outcome. We tested if the main association was different among the insurance-cost barrier variable. Binary logistic regression models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI).

Results

The odds of retinopathy decreased by 22 % in patients 46–64 years-of-age (OR 0.78; 95 CI 0.6–1.0) and 57 % in those 65+ (OR 0.43; 95 CI 0.28–0.65). The odds decreased by 39 % if female (OR 0.61; 95 CI 0.48–0.77). An increase in odds by 86 % (OR 1.86; 95 CI 1.07–3.21) occurred in other non-Hispanics, 50 % (OR 1.50; 95 CI 1.13–1.99) in black non-Hispanics and 70 % (OR 1.70; 95 CI 1.17–2.46) in Hispanics. There was no evidence that age at diagnosis of diabetes and presence of retinopathy varied by insurance cost (p > 0.05).

Conclusion

Health professionals may utilize these results to advocate for early disease intervention.
目的:研究医疗服务是否会改变糖尿病确诊年龄与视网膜病变患病率之间的关系:BRFSS 2020 调查数据来自 12,198 名成年人。排除了 "视网膜病变 "变量(569 人)和 "保险费用障碍 "变量(75 人)信息缺失的参与者。最终样本包括 11556 名参与者。糖尿病确诊年龄是主要暴露因素,视网膜病变是主要结果。我们测试了保险费用障碍变量之间的主要关联是否不同。我们使用二元逻辑回归模型计算了几率比(OR)和 95 % 的置信区间(CI):46-64岁患者发生视网膜病变的几率降低了22%(OR为0.78;95 CI为0.6-1.0),65岁以上患者发生视网膜病变的几率降低了57%(OR为0.43;95 CI为0.28-0.65)。如果是女性,几率会降低 39%(OR 0.61;95 CI 0.48-0.77)。其他非西班牙裔美国人的几率增加了 86%(OR 1.86;95 CI 1.07-3.21),非西班牙裔黑人的几率增加了 50%(OR 1.50;95 CI 1.13-1.99),西班牙裔美国人的几率增加了 70%(OR 1.70;95 CI 1.17-2.46)。没有证据表明糖尿病确诊年龄和视网膜病变的存在因保险费用而异(P > 0.05):结论:医疗专业人员可利用这些结果倡导早期疾病干预。
{"title":"The association between age at diagnosis of diabetes and development of diabetic retinopathy and assessment of healthcare access as an effect modifier","authors":"Bria L. George ,&nbsp;Alejandro M. Perez ,&nbsp;Pura Rodriguez ,&nbsp;Prashant Parekh ,&nbsp;Noël C. Barengo","doi":"10.1016/j.jdiacomp.2024.108931","DOIUrl":"10.1016/j.jdiacomp.2024.108931","url":null,"abstract":"<div><h3>Aims</h3><div>To examine if healthcare access modifies the association between age at diagnosis of diabetes and the prevalence of retinopathy.</div></div><div><h3>Methods</h3><div>BRFSS 2020 survey data was obtained from 12,198 adults. Participants with missing information in the variables “retinopathy” (<em>N</em> = 569) and “insurance-cost barrier” (<em>N</em> = 75) were excluded. The final sample included 11,556 participants. Age at diagnosis of diabetes was the main exposure and retinopathy was the main outcome. We tested if the main association was different among the insurance-cost barrier variable. Binary logistic regression models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI).</div></div><div><h3>Results</h3><div>The odds of retinopathy decreased by 22 % in patients 46–64 years-of-age (OR 0.78; 95 CI 0.6–1.0) and 57 % in those 65+ (OR 0.43; 95 CI 0.28–0.65). The odds decreased by 39 % if female (OR 0.61; 95 CI 0.48–0.77). An increase in odds by 86 % (OR 1.86; 95 CI 1.07–3.21) occurred in other non-Hispanics, 50 % (OR 1.50; 95 CI 1.13–1.99) in black non-Hispanics and 70 % (OR 1.70; 95 CI 1.17–2.46) in Hispanics. There was no evidence that age at diagnosis of diabetes and presence of retinopathy varied by insurance cost (<em>p</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>Health professionals may utilize these results to advocate for early disease intervention.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108931"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824348","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}
引用次数: 0
Contents/Barcode
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/S1056-8727(25)00015-7
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引用次数: 0
Behavioral health comorbidities in hospital outcomes post-lower extremity amputation in patients with type 1 and type 2 diabetes 1型和2型糖尿病患者下肢截肢后住院结果的行为健康合并症
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108949
Kelsey A. Schmittling
Peripheral artery disease leading to chronic limb threatening ischemia (CLTI) represents a significant concern for up to 11.0 % of patients with diabetes, often culminating in amputation of the affected limb. This retrospective cohort study explores frequency of comorbid behavioral health conditions (CBHCs) in patients with diabetes and hospital stay characteristics related to post-lower extremity amputation (LEA). Utilizing patient data from the Healthcare Cost and Utilization Project from 2020, patients were categorized into groups including having comorbid depression only, alcohol abuse only, drug abuse only, more than one CBHC, or no CBHC. On average, patients with at least one CBHC underwent LEA over three years earlier (59.3±12.0 years versus 62.6±12.1 years, respectively). A greater proportion of patients with at least one CBHC were non-Hispanic White people, reside in a county metro area <250,000 people, and were insured by Medicaid. Despite generally low mortality rates, patients with depression only display significantly higher survival rates relative to those without a CBHC. These findings begin exploring the socioeconomic complexities and healthcare disparities faced by patients with diabetes and behavioral health diagnoses, emphasizing the need for targeted preventive mental health screening and intervention prior to development of CLTI.
导致慢性肢体缺血(CLTI)的外周动脉疾病是多达 11.0% 的糖尿病患者的重大问题,通常会导致患肢截肢。这项回顾性队列研究探讨了糖尿病患者合并行为健康状况(CBHC)的频率以及与下肢截肢术后(LEA)相关的住院特征。研究利用 2020 年医疗成本与利用项目(Healthcare Cost and Utilization Project)中的患者数据,将患者分为几组,包括仅合并抑郁症、仅酗酒、仅药物滥用、一种以上 CBHC 或无 CBHC。平均而言,至少患有一种 CBHC 的患者接受 LEA 治疗的时间要早三年多(分别为 59.3±12.0 岁和 62.6±12.1 岁)。在至少有一个 CBHC 的患者中,非西班牙裔白人、居住在县级都会区的比例更高。
{"title":"Behavioral health comorbidities in hospital outcomes post-lower extremity amputation in patients with type 1 and type 2 diabetes","authors":"Kelsey A. Schmittling","doi":"10.1016/j.jdiacomp.2025.108949","DOIUrl":"10.1016/j.jdiacomp.2025.108949","url":null,"abstract":"<div><div>Peripheral artery disease leading to chronic limb threatening ischemia (CLTI) represents a significant concern for up to 11.0 % of patients with diabetes, often culminating in amputation of the affected limb. This retrospective cohort study explores frequency of comorbid behavioral health conditions (CBHCs) in patients with diabetes and hospital stay characteristics related to post-lower extremity amputation (LEA). Utilizing patient data from the Healthcare Cost and Utilization Project from 2020, patients were categorized into groups including having comorbid depression only, alcohol abuse only, drug abuse only, more than one CBHC, or no CBHC. On average, patients with at least one CBHC underwent LEA over three years earlier (59.3<span><math><mo>±</mo></math></span>12.0 years versus 62.6<span><math><mo>±</mo></math></span>12.1 years, respectively). A greater proportion of patients with at least one CBHC were non-Hispanic White people, reside in a county metro area &lt;250,000 people, and were insured by Medicaid. Despite generally low mortality rates, patients with depression only display significantly higher survival rates relative to those without a CBHC. These findings begin exploring the socioeconomic complexities and healthcare disparities faced by patients with diabetes and behavioral health diagnoses, emphasizing the need for targeted preventive mental health screening and intervention prior to development of CLTI.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108949"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970133","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}
引用次数: 0
Dapagliflozin has protective effects on palmitate-induced renal tubular epithelial cells by enhancing mitochondrial function and reducing oxidative stress 达格列净通过增强线粒体功能和减少氧化应激对棕榈酸诱导的肾小管上皮细胞具有保护作用。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2024.108930
Tingting Ding , Mingzhu Song , Sihong Wang , Chongbing Huang , Tianrong Pan
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly utilized for diabetic nephropathy, have demonstrated benefits beyond glucose control, including organ protection. This study investigated the protective effects of the SGLT2 inhibitor, dapagliflozin (DAPA), on palmitate-induced renal tubular epithelial cell (HK−2) injury, particularly concentrating on mitochondrial function and oxidative stress. HK-2 cells were treated with 150 μmol/L palmitate to induce mitochondrial dysfunction and oxidative stress, and they were co-treated with 2 μmol/L DAPA for 24 h. DAPA significantly increased cell viability (P < 0.05), reduced reactive oxygen species (ROS) levels (P < 0.001), and restored mitochondrial membrane potential (P < 0.05). It also lowered malondialdehyde (MDA) level (P < 0.001) and increased superoxide dismutase (SOD) expression level (P < 0.001). Western blot analysis revealed that DAPA reversed palmitate-induced upregulation of apoptosis-related proteins, including Bax and Cytochrome C. DAPA also mitigated the overactivation of autophagy-related proteins, such as LC3 and Beclin-1, indicating its role in modulating autophagy under diabetic nephropathy. Electron microscopy confirmed improvements in mitochondrial morphology, accompanying by reduced swelling and restored cristae structure. These findings highlight the potential of DAPA, as an SGLT2 inhibitor, to mitigate renal injury by enhancing mitochondrial function and reducing oxidative stress, providing novel insights into its therapeutic value for diabetic nephropathy management.
钠-葡萄糖协同转运体 2(SGLT2)抑制剂是糖尿病肾病的常用治疗药物,除了控制血糖外,还具有保护器官等功效。本研究调查了 SGLT2 抑制剂达帕格列净(DAPA)对棕榈酸酯诱导的肾小管上皮细胞(HK-2)损伤的保护作用,尤其是对线粒体功能和氧化应激的保护作用。用150 μmol/L棕榈酸酯处理HK-2细胞以诱导线粒体功能障碍和氧化应激,然后用2 μmol/L DAPA处理24 h。
{"title":"Dapagliflozin has protective effects on palmitate-induced renal tubular epithelial cells by enhancing mitochondrial function and reducing oxidative stress","authors":"Tingting Ding ,&nbsp;Mingzhu Song ,&nbsp;Sihong Wang ,&nbsp;Chongbing Huang ,&nbsp;Tianrong Pan","doi":"10.1016/j.jdiacomp.2024.108930","DOIUrl":"10.1016/j.jdiacomp.2024.108930","url":null,"abstract":"<div><div>Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly utilized for diabetic nephropathy, have demonstrated benefits beyond glucose control, including organ protection. This study investigated the protective effects of the SGLT2 inhibitor, dapagliflozin (DAPA), on palmitate-induced renal tubular epithelial cell (HK−2) injury, particularly concentrating on mitochondrial function and oxidative stress. HK-2 cells were treated with 150 μmol/L palmitate to induce mitochondrial dysfunction and oxidative stress, and they were co-treated with 2 μmol/L DAPA for 24 h. DAPA significantly increased cell viability (<em>P</em> &lt; 0.05), reduced reactive oxygen species (ROS) levels (<em>P</em> &lt; 0.001), and restored mitochondrial membrane potential (<em>P</em> &lt; 0.05). It also lowered malondialdehyde (MDA) level (<em>P</em> &lt; 0.001) and increased superoxide dismutase (SOD) expression level (<em>P</em> &lt; 0.001). Western blot analysis revealed that DAPA reversed palmitate-induced upregulation of apoptosis-related proteins, including Bax and Cytochrome C. DAPA also mitigated the overactivation of autophagy-related proteins, such as LC3 and Beclin-1, indicating its role in modulating autophagy under diabetic nephropathy. Electron microscopy confirmed improvements in mitochondrial morphology, accompanying by reduced swelling and restored cristae structure. These findings highlight the potential of DAPA, as an SGLT2 inhibitor, to mitigate renal injury by enhancing mitochondrial function and reducing oxidative stress, providing novel insights into its therapeutic value for diabetic nephropathy management.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108930"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uric acid in diabetic microvascular complications: Mechanisms and therapy 尿酸在糖尿病微血管并发症中的作用:机制和治疗。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2024.108929
Xin Li, Bo Huang, Yue Liu, Meng Wang, Jing-Qiu Cui
Uric acid (UA) is mainly synthesized in the liver, intestine, and vascular endothelium and excreted by the kidney (70 %) and intestine (30 %). Hyperuricemia (HUA) occurs when UA production exceeds excretion. Many studies have found that elevated UA is associated with diabetic microvascular complications (DMC), including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). In addition, too high or too low UA levels will promote the occurrence and development of chronic diseases, but the relationship between UA and diabetic microvascular complications (DMC) is not clear. Therefore, the rational treatment of UA in patients with diabetes is essential. In this review, we summarize and discuss the mechanism and treatment of UA and DMC and may provide potential advice for rational drug selection.
尿酸(UA)主要由肝脏、肠道和血管内皮合成,由肾脏(70%)和肠道(30%)排出体外。当尿酸生成量超过排泄量时,就会出现高尿酸血症(HUA)。许多研究发现,尿酸升高与糖尿病微血管并发症(DMC)有关,包括糖尿病视网膜病变(DR)、糖尿病肾病(DN)和糖尿病周围神经病变(DPN)。此外,UA 水平过高或过低都会促进慢性疾病的发生和发展,但 UA 与糖尿病微血管并发症(DMC)之间的关系尚不明确。因此,合理治疗糖尿病患者的尿酸至关重要。在这篇综述中,我们总结并讨论了 UA 与 DMC 的机制和治疗方法,为合理选药提供了可能的建议。
{"title":"Uric acid in diabetic microvascular complications: Mechanisms and therapy","authors":"Xin Li,&nbsp;Bo Huang,&nbsp;Yue Liu,&nbsp;Meng Wang,&nbsp;Jing-Qiu Cui","doi":"10.1016/j.jdiacomp.2024.108929","DOIUrl":"10.1016/j.jdiacomp.2024.108929","url":null,"abstract":"<div><div>Uric acid (UA) is mainly synthesized in the liver, intestine, and vascular endothelium and excreted by the kidney (70 %) and intestine (30 %). Hyperuricemia (HUA) occurs when UA production exceeds excretion. Many studies have found that elevated UA is associated with diabetic microvascular complications (DMC), including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). In addition, too high or too low UA levels will promote the occurrence and development of chronic diseases, but the relationship between UA and diabetic microvascular complications (DMC) is not clear. Therefore, the rational treatment of UA in patients with diabetes is essential. In this review, we summarize and discuss the mechanism and treatment of UA and DMC and may provide potential advice for rational drug selection.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108929"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of three diagnostic glycemic measures with all-cause and cardiovascular mortality in people not on antidiabetic medications: A prospective cohort study
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-30 DOI: 10.1016/j.jdiacomp.2025.108970
Jiayue Zhang , Wenxiao Zheng , Shuting Wang , Xiangyang Gao , Ying Xiao , Zuyao Yang

Objective

This study aimed to investigate the value of three diagnostic glycemic measures, i.e., 2-hour plasma glucose (2hPG) during 75-g oral glucose tolerance test, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c), in predicting risk of all-cause and cardiovascular mortality after adjusting for the influence of these glycemic measures on each other.

Methods

A total of 14,013 U.S. adults who were not on antidiabetic medications when recruited were identified from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2005–2016. High blood glucose was defined as 2hPG ≥11.1 mmol/L, FPG ≥7.0 mmol/L, or HbA1c ≥6.5 %, according to the American Diabetes Association 2023 standards. Two approaches were adopted to examine the value of each glycemic measure in predicting mortality risk while controlling the influence of the other two measures: (1) adjusting for 2hPG, HbA1c, and FPG in the same model, and (2) comparing individuals showing isolated elevation of 2hPG, HbA1c, or FPG with those being “normal” for all the three measures. Major non-glycemic risk factors were adjusted for in the multivariable regression analyses.

Results

During a median follow-up of 9.8 years, 2869 participants died, and 960 of the deaths were attributed to cardiovascular causes. When included in the model individually, elevated 2hPG, FPG, and HbA1c were all predictive of both all-cause and cardiovascular mortality (adjusted hazard ratios ranging from 1.32 to 1.55, all p values <0.05). After controlling the influence of the other two glycemic measures, elevated 2hPG was still statistically significantly associated with the outcomes (adjusted hazard ratios ranging from 1.04 to 1.33, depending on analytical approaches), whereas elevated FPG was not, and HbA1c was associated with cardiovascular mortality only when treated as a continuous variable and when 2hPG and FPG levels were in the normal range (adjusted hazard ratio 1.27 [1.04–1.55] for 1 % increase in HbA1c).

Conclusions

2hPG, FPG, and HbA1c were all predictive of all-cause and cardiovascular mortality when used alone, but when combined only 2hPG retained its predictive value for both outcomes while HbA1c predicted cardiovascular mortality only when used as a continuous variable and when 2hPG and FPG were in the normal range.
{"title":"Associations of three diagnostic glycemic measures with all-cause and cardiovascular mortality in people not on antidiabetic medications: A prospective cohort study","authors":"Jiayue Zhang ,&nbsp;Wenxiao Zheng ,&nbsp;Shuting Wang ,&nbsp;Xiangyang Gao ,&nbsp;Ying Xiao ,&nbsp;Zuyao Yang","doi":"10.1016/j.jdiacomp.2025.108970","DOIUrl":"10.1016/j.jdiacomp.2025.108970","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the value of three diagnostic glycemic measures, i.e., 2-hour plasma glucose (2hPG) during 75-g oral glucose tolerance test, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c), in predicting risk of all-cause and cardiovascular mortality after adjusting for the influence of these glycemic measures on each other.</div></div><div><h3>Methods</h3><div>A total of 14,013 U.S. adults who were not on antidiabetic medications when recruited were identified from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2005–2016. High blood glucose was defined as 2hPG ≥11.1 mmol/L, FPG ≥7.0 mmol/L, or HbA1c ≥6.5 %, according to the American Diabetes Association 2023 standards. Two approaches were adopted to examine the value of each glycemic measure in predicting mortality risk while controlling the influence of the other two measures: (1) adjusting for 2hPG, HbA1c, and FPG in the same model, and (2) comparing individuals showing isolated elevation of 2hPG, HbA1c, or FPG with those being “normal” for all the three measures. Major non-glycemic risk factors were adjusted for in the multivariable regression analyses.</div></div><div><h3>Results</h3><div>During a median follow-up of 9.8 years, 2869 participants died, and 960 of the deaths were attributed to cardiovascular causes. When included in the model individually, elevated 2hPG, FPG, and HbA1c were all predictive of both all-cause and cardiovascular mortality (adjusted hazard ratios ranging from 1.32 to 1.55, all <em>p</em> values &lt;0.05). After controlling the influence of the other two glycemic measures, elevated 2hPG was still statistically significantly associated with the outcomes (adjusted hazard ratios ranging from 1.04 to 1.33, depending on analytical approaches), whereas elevated FPG was not, and HbA1c was associated with cardiovascular mortality only when treated as a continuous variable and when 2hPG and FPG levels were in the normal range (adjusted hazard ratio 1.27 [1.04–1.55] for 1 % increase in HbA1c).</div></div><div><h3>Conclusions</h3><div>2hPG, FPG, and HbA1c were all predictive of all-cause and cardiovascular mortality when used alone, but when combined only 2hPG retained its predictive value for both outcomes while HbA1c predicted cardiovascular mortality only when used as a continuous variable and when 2hPG and FPG were in the normal range.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108970"},"PeriodicalIF":2.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143098442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of diabetes and its complications
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