Journal of diabetes and its complications最新文献

FIB-4 predicts events in compensated advanced chronic liver disease and type 2 diabetes treated with GLP-1-receptor-agonists

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-21 DOI: 10.1016/j.jdiacomp.2025.108978

Wiebke van Beurden , Yuly P. Mendoza , Naomi F. Lange , Jaime Bosch , Annalisa Berzigotti , Susana G. Rodrigues

Background & aims

Patients with compensated advanced chronic liver disease (cACLD) and treated type 2 diabetes have an increased risk for liver-related events, but data regarding this population is lacking, particularly, taking into account novel treatments. We assessed the role of Fibrosis-4 index and other variables to predict events.

Methods

First hepatic decompensation, liver transplantation (OLT), death, hepatocellular carcinoma (HCC) and bacterial infections over a follow-up period of 28.7 (16–49.4) months were retrospectively identified from 106 patients with treated type 2 diabetes and liver stiffness measurement >10 kPa suggesting ACLD. We identified predictors of events using Cox regression. Additionally, we evaluated treatment effect with add-on GLP-1 receptor agonists (GLP-1-RA) compared to other antidiabetic medications.

Results

FIB-4 was associated with hepatic decompensation, OLT and death (HR 1.517, 95%CI 1.226–1.879, p ≤ 0.001), HCC (HR 1.369, 95%CI 1.046–1.791, p = 0.022) and bacterial infections (HR 1.379, 95%CI 1.118–1.702, p = 0.003). Propensity score adjusted analysis for GLP-1-RA treatment did not show an effect (HR 0.240, 95%CI 0.044–1.315, p = 0.1). Survival was worse in those with more advanced disease defined by FIB-4 > 2.67 (p = 0.02).

Conclusion

FIB-4 is a strong prognostic tool to screen patients and refer them to specialists, in cACLD patients and pharmacologically treated type 2 diabetes, irrespective of treatment.

{"title":"FIB-4 predicts events in compensated advanced chronic liver disease and type 2 diabetes treated with GLP-1-receptor-agonists","authors":"Wiebke van Beurden , Yuly P. Mendoza , Naomi F. Lange , Jaime Bosch , Annalisa Berzigotti , Susana G. Rodrigues","doi":"10.1016/j.jdiacomp.2025.108978","DOIUrl":"10.1016/j.jdiacomp.2025.108978","url":null,"abstract":"<div><h3>Background & aims</h3><div>Patients with compensated advanced chronic liver disease (cACLD) and treated type 2 diabetes have an increased risk for liver-related events, but data regarding this population is lacking, particularly, taking into account novel treatments. We assessed the role of Fibrosis-4 index and other variables to predict events.</div></div><div><h3>Methods</h3><div>First hepatic decompensation, liver transplantation (OLT), death, hepatocellular carcinoma (HCC) and bacterial infections over a follow-up period of 28.7 (16–49.4) months were retrospectively identified from 106 patients with treated type 2 diabetes and liver stiffness measurement >10 kPa suggesting ACLD. We identified predictors of events using Cox regression. Additionally, we evaluated treatment effect with add-on GLP-1 receptor agonists (GLP-1-RA) compared to other antidiabetic medications.</div></div><div><h3>Results</h3><div>FIB-4 was associated with hepatic decompensation, OLT and death (HR 1.517, 95%CI 1.226–1.879, <em>p</em> ≤ 0.001), HCC (HR 1.369, 95%CI 1.046–1.791, <em>p</em> = 0.022) and bacterial infections (HR 1.379, 95%CI 1.118–1.702, <em>p</em> = 0.003). Propensity score adjusted analysis for GLP-1-RA treatment did not show an effect (HR 0.240, 95%CI 0.044–1.315, <em>p</em> = 0.1). Survival was worse in those with more advanced disease defined by FIB-4 > 2.67 (<em>p</em> = 0.02).</div></div><div><h3>Conclusion</h3><div>FIB-4 is a strong prognostic tool to screen patients and refer them to specialists, in cACLD patients and pharmacologically treated type 2 diabetes, irrespective of treatment.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108978"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479294","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

Pharmacological effect of ZYGK1, a novel glucokinase activator, in hyperglycemic and sulfonylurea-resistant type 2 diabetes in mice models

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-19 DOI: 10.1016/j.jdiacomp.2025.108977

Kalpesh Patani , Amit Joharapurkar , Rajesh Sundar , Samadhan Kshirsagar , Sunil Metiya , Ashutosh Kumar , Mukul Jain

Objectives

Type 2 diabetes is caused due to inadequate glucose utilization in the liver and pancreas due to insulin resistance. Glucokinase enzyme plays a key role in metabolism of glucose and insulin release and hence glucokinase activation can be a useful therapeutic target for treatment of type 2 diabetes.

Methods

Present study was conducted to investigate the effect of a novel glucokinase activator ZYGK1 in the preclinical models of diabetes in mice. The activity of ZYGK1 was evaluated using recombinant glucokinase, and isolated islets and hepatocytes. Acute effect on glucose disposal was evaluated in C57 mice and repeated dose effect was assessed in db/db mice, along with the evaluation in sulfonylurea-resistance db/db mice.

Results

ZYGK1 has potent glucokinase stimulating activity with EC50 of 43 nM and increased glucokinase activity in islets and hepatocytes in a dose-related manner. Oral administration of ZYGK1 (0.1 to 10 mg/kg) showed dose dependently improved glucose disposal and glucose dependent insulin secretion in oral glucose tolerance test (OGTT) in C57 mice. Repeated dose administration of ZYGK1 improved glucose homeostasis and nondiabetic as well as diabetic mice and sulfonylurea-resistant db/db mice.

Conclusion

ZYGK1 appears to be a potential therapeutic option for the treatment of type 2 diabetes owing to its action in the liver and pancreas, and in conditions resistant to sulfonylurea therapy.

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引用次数: 0

Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-19 DOI: 10.1016/j.jdiacomp.2025.108975

Qian Xu , Xuan Qiu , Hailing Di , Zhongkang Li , Zanchao Liu , Kuanzhi Liu

Objective

Beyond its established glucose-lowering and weight-reducing benefits, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as liraglutide may also mitigate sarcopenia. This study investigates the effects of liraglutide on diabetic sarcopenia and its underlying mechanisms.

Methods

A type 2 diabetic SD rat model was induced using a high-fat, high-sugar diet supplemented with a low dose of streptozotocin. Comparisons were made among control (Con), diabetic (DM), and liraglutide-treated (Li) groups for gastrocnemius muscle wet weight and length, histology (HE staining), immunofluorescence for muscle fiber typing, and Western blotting for aging-related proteins and YAP/TAZ pathway components. Concurrently, C2C12 myoblasts were differentiated into myotubes, treated with 60 mM glucose to model diabetic conditions, and assessed for morphological changes, senescence (SA-β-gal staining), and protein expression dynamics.

Results

Diabetic rats displayed significant reductions in muscle mass, length, and cross-sectional area, along with disorganized fiber architecture, all of which were improved by liraglutide. In vitro, C2C12 myotubes showed accelerated aging and atrophy under high-glucose conditions, which were significantly reduced by liraglutide. Analysis revealed increased expression of aging markers P53 and P21 and decreased YAP/TAZ/TEAD and Cyclin D1 levels in diabetic conditions, which were reversed following liraglutide treatment. The inhibition of YAP significantly negated the protective effects of liraglutide.

Conclusion

High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways.

{"title":"Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway","authors":"Qian Xu , Xuan Qiu , Hailing Di , Zhongkang Li , Zanchao Liu , Kuanzhi Liu","doi":"10.1016/j.jdiacomp.2025.108975","DOIUrl":"10.1016/j.jdiacomp.2025.108975","url":null,"abstract":"<div><h3>Objective</h3><div>Beyond its established glucose-lowering and weight-reducing benefits, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as liraglutide may also mitigate sarcopenia. This study investigates the effects of liraglutide on diabetic sarcopenia and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A type 2 diabetic SD rat model was induced using a high-fat, high-sugar diet supplemented with a low dose of streptozotocin. Comparisons were made among control (Con), diabetic (DM), and liraglutide-treated (Li) groups for gastrocnemius muscle wet weight and length, histology (HE staining), immunofluorescence for muscle fiber typing, and Western blotting for aging-related proteins and YAP/TAZ pathway components. Concurrently, C2C12 myoblasts were differentiated into myotubes, treated with 60 mM glucose to model diabetic conditions, and assessed for morphological changes, senescence (SA-β-gal staining), and protein expression dynamics.</div></div><div><h3>Results</h3><div>Diabetic rats displayed significant reductions in muscle mass, length, and cross-sectional area, along with disorganized fiber architecture, all of which were improved by liraglutide. In vitro, C2C12 myotubes showed accelerated aging and atrophy under high-glucose conditions, which were significantly reduced by liraglutide. Analysis revealed increased expression of aging markers P53 and P21 and decreased YAP/TAZ/TEAD and Cyclin D1 levels in diabetic conditions, which were reversed following liraglutide treatment. The inhibition of YAP significantly negated the protective effects of liraglutide.</div></div><div><h3>Conclusion</h3><div>High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108975"},"PeriodicalIF":2.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463747","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

Oral edaravone ameliorates myocardial fibrosis in type 2 diabetic rats by TGF-β1/Smad signaling pathway

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-19 DOI: 10.1016/j.jdiacomp.2025.108976

Xiao-Yan Zhang , Yong-xuan Xu , Si-Quan Xue , Yue-Qin Zeng , Juan-Hua Gu , Xin-Fu Zhou , Hai-Yun Luo , Li-Jin Pu

Myocardial fibrosis, characterized by increased reactive oxygen species (ROS), is a key pathological feature of diabetic cardiomyopathy (DCM). Although oral edaravone (EDA) shows therapeutic potential in ameliorating myocardial fibrosis in DCM, the precise mechanisms remain unclear. Transcriptome analysis of myocardial tissues revealed a dramatic up-regulation of the TGF-β1/Smad pathway, which was reversed by oral EDA treatment. In vitro studies showed that oral EDA attenuated myocardial fibrosis by inhibiting the TGF-β1/Smad signaling pathway and its downstream fibrosis key factors, Col3a1 and α-SMA. These findings suggest that oral EDA improves myocardial fibrosis in Type 2 diabetes mellitus (T2DM) by inhibiting the TGF-β1/Smad signaling pathway and holds promise as an effective treatment for myocardial fibrosis in DCM.

引用次数: 0

Highlighting the complex relationship between diabetes, renal function and bone health

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-19 DOI: 10.1016/j.jdiacomp.2025.108974

Joseph C. Lee , Jia Wen Chong , Shanal Kumar

引用次数: 0

The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers - A literature review

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-13 DOI: 10.1016/j.jdiacomp.2025.108973

Ken Mackay, Rhiannon Thompson, Matthew Parker, James Pedersen, Hayden Kelly, Mairi Loynd, Emily Giffen, Angus Baker

Diabetic Foot Ulcers (DFUs) are chronic foot wounds, in a person with diabetes, which are associated with peripheral arterial insufficiency and/or peripheral neuropathy of the lower limb. Recent UK audit figures report that approximately 50–60 % of DFUs remain unhealed after 12 weeks. Previous research has suggested that ischaemia plays a key role in the pathophysiology of many chronic wounds, including DFUs. For this reason, hyperbaric oxygen therapy (HOT) has been investigated. The study aimed to investigate 1) Current understanding of the physiology of normal wound healing and the pathological mechanisms that occur in DFUs to interrupt these processes; 2) Effectiveness of current DFU treatment approaches; 3) Effectiveness from clinical trials and meta-analyses for any demonstrated therapeutic benefits of HOT in the treatment of DFUs, 4) Patient selection criteria for HOT, and patients who stand to benefit most from treatment.

The review found that wound healing is a complex process, involving many cells and signalling molecules, and it remains incompletely understood. However, current evidence suggests that hyperglycaemia, hypoxia, chronic inflammation (due to infection, immune-cell dysfunction or other causes), peripheral neuropathy, and macro- and micro-vascular dysfunction may all adversely affect DFU healing. The review found that current NICE guidelines do not approve HOT therapy in the UK for DFU's, despite encouraging clinical research findings. HOT shows theoretical promise and has been successfully used in the treatment of individual DFUs for several decades. Despite this, there remains a lack of strong clinical evidence of benefits to encourage HOT's wider use. The review found that there were four important patient selection criteria for HOT treatment, including glycaemic control, possible contraindications and complications associated with treatment, ulcer severity and resistance to first and second line treatments. The review concluded that further high-quality clinical research is needed to improve the evidence base.

{"title":"The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers - A literature review","authors":"Ken Mackay, Rhiannon Thompson, Matthew Parker, James Pedersen, Hayden Kelly, Mairi Loynd, Emily Giffen, Angus Baker","doi":"10.1016/j.jdiacomp.2025.108973","DOIUrl":"10.1016/j.jdiacomp.2025.108973","url":null,"abstract":"<div><div>Diabetic Foot Ulcers (DFUs) are chronic foot wounds, in a person with diabetes, which are associated with peripheral arterial insufficiency and/or peripheral neuropathy of the lower limb. Recent UK audit figures report that approximately 50–60 % of DFUs remain unhealed after 12 weeks. Previous research has suggested that ischaemia plays a key role in the pathophysiology of many chronic wounds, including DFUs. For this reason, hyperbaric oxygen therapy (HOT) has been investigated. The study aimed to investigate 1) Current understanding of the physiology of normal wound healing and the pathological mechanisms that occur in DFUs to interrupt these processes; 2) Effectiveness of current DFU treatment approaches; 3) Effectiveness from clinical trials and meta-analyses for any demonstrated therapeutic benefits of HOT in the treatment of DFUs, 4) Patient selection criteria for HOT, and patients who stand to benefit most from treatment.</div><div>The review found that wound healing is a complex process, involving many cells and signalling molecules, and it remains incompletely understood. However, current evidence suggests that hyperglycaemia, hypoxia, chronic inflammation (due to infection, immune-cell dysfunction or other causes), peripheral neuropathy, and macro- and micro-vascular dysfunction may all adversely affect DFU healing. The review found that current NICE guidelines do not approve HOT therapy in the UK for DFU's, despite encouraging clinical research findings. HOT shows theoretical promise and has been successfully used in the treatment of individual DFUs for several decades. Despite this, there remains a lack of strong clinical evidence of benefits to encourage HOT's wider use. The review found that there were four important patient selection criteria for HOT treatment, including glycaemic control, possible contraindications and complications associated with treatment, ulcer severity and resistance to first and second line treatments. The review concluded that further high-quality clinical research is needed to improve the evidence base.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108973"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430008","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

Implementation of evidence-based foot screening in people with diabetes: A scoping review

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-12 DOI: 10.1016/j.jdiacomp.2025.108972

Jemma M. Houghton , Matthew C. Hynes , Nia W. Roberts , Helene-Mari van der Westhuizen , Joel A. Dave , Andrew Farmer

Background

Recommendations to prevent diabetes ulceration and amputation include an annual foot check, primarily screening for sensation and circulation. Using these simple, evidence-based components is vital to identifying complications early, assessing risk, and managing care to prevent or delay amputations. However, routine implementation of these assessments is suboptimal and approaches to their integration remain poorly understood.

Aim

We aimed to identify and synthesize information on the factors affecting implementation of simple evidence-based diabetes foot screening.

Methods

We reviewed published and grey literature using a blinded two-stage process by two independent reviewers. Included studies were primary research that implemented or improved foot screening for adults with type 1 or 2 diabetes, assessing at least one of the following: 10-g monofilament sensitivity, pedal pulse palpation, or history of ulceration or amputation. A thematic synthesis approach was used.

Results

We screened 5133 titles and abstracts, reviewed 102 full-text articles, and included 26 studies in the final analysis. We identified four key themes: (1) Existing diabetes screening (i.e. retinal screening) or treatment interventions (i.e. medication collection) provide opportunities for synergistic integration; (2) Annual event-based foot screening (e.g. on World Diabetes Day) in lower resource settings provides community-focused preventative care; (3) Further opportunities to increase access to foot screening include self-administered screening and screening in complex residential settings; (4) Healthcare provider champions are essential for local foot screening implementation in primary and secondary care.

Conclusion

Further research should evaluate the issues identified in these four themes, in different contexts, and with support of implementation frameworks.

{"title":"Implementation of evidence-based foot screening in people with diabetes: A scoping review","authors":"Jemma M. Houghton , Matthew C. Hynes , Nia W. Roberts , Helene-Mari van der Westhuizen , Joel A. Dave , Andrew Farmer","doi":"10.1016/j.jdiacomp.2025.108972","DOIUrl":"10.1016/j.jdiacomp.2025.108972","url":null,"abstract":"<div><h3>Background</h3><div>Recommendations to prevent diabetes ulceration and amputation include an annual foot check, primarily screening for sensation and circulation. Using these simple, evidence-based components is vital to identifying complications early, assessing risk, and managing care to prevent or delay amputations. However, routine implementation of these assessments is suboptimal and approaches to their integration remain poorly understood.</div></div><div><h3>Aim</h3><div>We aimed to identify and synthesize information on the factors affecting implementation of simple evidence-based diabetes foot screening.</div></div><div><h3>Methods</h3><div>We reviewed published and grey literature using a blinded two-stage process by two independent reviewers. Included studies were primary research that implemented or improved foot screening for adults with type 1 or 2 diabetes, assessing at least one of the following: 10-<em>g</em> monofilament sensitivity, pedal pulse palpation, or history of ulceration or amputation. A thematic synthesis approach was used.</div></div><div><h3>Results</h3><div>We screened 5133 titles and abstracts, reviewed 102 full-text articles, and included 26 studies in the final analysis. We identified four key themes: (1) Existing diabetes screening (i.e. retinal screening) or treatment interventions (i.e. medication collection) provide opportunities for synergistic integration; (2) Annual event-based foot screening (e.g. on World Diabetes Day) in lower resource settings provides community-focused preventative care; (3) Further opportunities to increase access to foot screening include self-administered screening and screening in complex residential settings; (4) Healthcare provider champions are essential for local foot screening implementation in primary and secondary care.</div></div><div><h3>Conclusion</h3><div>Further research should evaluate the issues identified in these four themes, in different contexts, and with support of implementation frameworks.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 3","pages":"Article 108972"},"PeriodicalIF":2.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403412","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

Kidney fat by magnetic resonance spectroscopy in type 2 diabetes with chronic kidney disease 磁共振波谱分析2型糖尿病合并慢性肾病患者的肾脏脂肪。

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2024.108923

Niels Sondergaard Heinrich , Rune Ploegstra Pedersen , Mark Bitsch Vestergaard , Ulrich Lindberg , Ulrik Bjørn Andersen , Bryan Haddock , Alessia Fornoni , Henrik Bo Wiberg Larsson , Peter Rossing , Tine Willum Hansen

Background and hypothesis

The kidneys may be susceptible to ectopic fat and its lipotoxic effects, disposing them to chronic kidney disease (CKD) in type 2 diabetes (T2D). We investigated whether the kidney parenchyma fat content and kidney sinus fat volume would be higher in persons with T2D and CKD.

Methods

Cross-sectional study including 29 controls, 27 persons with T2D and no CKD, and 48 persons with T2D and early CKD (urine albumin creatinine ratio (UACR) ≥ 30 mg/g). Kidney parenchyma fat content and kidney sinus fat volume were assessed using magnetic resonance spectroscopy and Dixon scans respectively.

Results

In the control, T2D without CKD and T2D with CKD groups, respectively, median [1st – 3rd quartile] UACR was 5 [4 – 6], 6 [5 – 10] and 95 [43 – 278] mg/g. and mean ± standard deviation estimated glomerular filtration rate was 89 ± 11, 94 ± 11 and 77 ± 22 ml/min/1.73m². Kidney parenchyma fat content was, respectively, 1.0 [0.5–2.4], 0.7 [0.2–1.2], 1.0 [0.3–2.0] % (p = 0.26). Kidney sinus fat volume was 2.8 [1.6–7.6], 8.0 [4.7–11.3], 10.3 [5.7–14.0] ml (p < 0.01). Around 90 % of T2D participants received a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist.

Conclusions

In a setting of modern, multifactorial T2D management, kidney parenchyma fat content, evaluated with magnetic resonance spectroscopy, was similar among healthy controls and persons with T2D irrespective of CKD status. Still, kidney sinus fat volume was higher in the presence of T2D and higher still with CKD.

背景和假设：2型糖尿病（T2D）患者的肾脏可能易受异位脂肪及其脂毒性作用的影响，从而导致慢性肾脏病（CKD）。我们研究了 T2D 和 CKD 患者的肾实质脂肪含量和肾窦脂肪体积是否会更高：方法：横断面研究，包括 29 名对照组、27 名 T2D 和无 CKD 患者，以及 48 名 T2D 和早期 CKD 患者（尿白蛋白肌酐比值 (UACR) ≥ 30 mg/g）。分别使用磁共振波谱和迪克森扫描评估肾脏实质脂肪含量和肾窦脂肪体积：对照组、无 CKD 的 T2D 组和有 CKD 的 T2D 组的 UACR 中位数[第 1 - 第 3 四分位数]分别为 5 [4 - 6]、6 [5 - 10] 和 95 [43 - 278] mg/g，估计肾小球滤过率的平均值（± 标准差）分别为 89 ± 11、94 ± 11 和 77 ± 22 ml/min/1.73m2。肾实质脂肪含量分别为 1.0 [0.5-2.4]、0.7 [0.2-1.2]、1.0 [0.3-2.0]%（p = 0.26）。肾窦脂肪量分别为 2.8 [1.6-7.6]、8.0 [4.7-11.3]、10.3 [5.7-14.0]毫升（p 结论：肾窦脂肪量的变化与肾脏的功能有关：在现代多因素 T2D 管理环境下，无论 CKD 状态如何，健康对照组和 T2D 患者的肾脏实质脂肪含量（通过磁共振波谱进行评估）相似。不过，患有 T2D 的肾窦脂肪量更高，而患有 CKD 的肾窦脂肪量更高。

{"title":"Kidney fat by magnetic resonance spectroscopy in type 2 diabetes with chronic kidney disease","authors":"Niels Sondergaard Heinrich , Rune Ploegstra Pedersen , Mark Bitsch Vestergaard , Ulrich Lindberg , Ulrik Bjørn Andersen , Bryan Haddock , Alessia Fornoni , Henrik Bo Wiberg Larsson , Peter Rossing , Tine Willum Hansen","doi":"10.1016/j.jdiacomp.2024.108923","DOIUrl":"10.1016/j.jdiacomp.2024.108923","url":null,"abstract":"<div><h3>Background and hypothesis</h3><div>The kidneys may be susceptible to ectopic fat and its lipotoxic effects, disposing them to chronic kidney disease (CKD) in type 2 diabetes (T2D). We investigated whether the kidney parenchyma fat content and kidney sinus fat volume would be higher in persons with T2D and CKD.</div></div><div><h3>Methods</h3><div>Cross-sectional study including 29 controls, 27 persons with T2D and no CKD, and 48 persons with T2D and early CKD (urine albumin creatinine ratio (UACR) ≥ 30 mg/g). Kidney parenchyma fat content and kidney sinus fat volume were assessed using magnetic resonance spectroscopy and Dixon scans respectively.</div></div><div><h3>Results</h3><div>In the control, T2D without CKD and T2D with CKD groups, respectively, median [1st – 3rd quartile] UACR was 5 [4 – 6], 6 [5 – 10] and 95 [43 – 278] mg/g. and mean ± standard deviation estimated glomerular filtration rate was 89 ± 11, 94 ± 11 and 77 ± 22 ml/min/1.73m<sup>2</sup>. Kidney parenchyma fat content was, respectively, 1.0 [0.5–2.4], 0.7 [0.2–1.2], 1.0 [0.3–2.0] % (<em>p</em> = 0.26). Kidney sinus fat volume was 2.8 [1.6–7.6], 8.0 [4.7–11.3], 10.3 [5.7–14.0] ml (<em>p</em> < 0.01). Around 90 % of T2D participants received a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist.</div></div><div><h3>Conclusions</h3><div>In a setting of modern, multifactorial T2D management, kidney parenchyma fat content, evaluated with magnetic resonance spectroscopy, was similar among healthy controls and persons with T2D irrespective of CKD status. Still, kidney sinus fat volume was higher in the presence of T2D and higher still with CKD.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108923"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794717","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

Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study 2型糖尿病患者脂蛋白相关磷脂酶A2与糖尿病周围神经病变的相关性：一项横断面研究

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108950

Yijia He , Miaomin Ye , Ziyang Shen, Ziyi Zhong, Yin Xia, Qian Li

Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme implicated in inflammation and oxidative stress, and has been associated with cardiovascular conditions and adverse outcomes, particularly in diabetes and its complications. However, no prior studies have examined the relationship between Lp-PLA2 and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This research aims to explore the potential association between Lp-PLA2 and DPN.

Methods

This retrospective study included 880 hospitalized patients with T2DM treated between March 2024 and August 2024 at Nanjing First Hospital. To assess the relationship between Lp-PLA2 and DPN, multiple logistic regression models were applied. The study also utilized restricted cubic spline (RCS) modeling, segmented regression, stratified analysis, and receiver operating characteristic (ROC) curve assessments.

Results

Patients diagnosed with DPN exhibited elevated Lp-PLA2 levels compared to those without DPN. Even after adjusting for multiple variables, Lp-PLA2 was independently associated with a higher likelihood of DPN (odds ratio [OR] 1.011, 95 % confidence interval [CI] 1.008–1.014, P < 0.001). The RCS analysis revealed a nonlinear association, with an inflection point at 215.8 ng/mL. In ROC curve analysis, the area under the curve (AUC) for Lp-PLA2 was 0.664, while the combined indicator AUC was 0.739.

Conclusions

Serum Lp-PLA2 levels show a significant correlation with the presence of DPN in patients with T2DM. These findings suggest that Lp-PLA2 could serve as a valuable biomarker for identifying patients at risk for DPN, emphasizing the need for close monitoring of T2DM individuals with elevated Lp-PLA2 to mitigate the risk of developing DPN and associated adverse health outcomes.

背景：脂蛋白相关磷脂酶A2 （Lp-PLA2）是一种与炎症和氧化应激有关的酶，与心血管疾病和不良结局有关，特别是在糖尿病及其并发症中。然而，之前没有研究调查Lp-PLA2与2型糖尿病（T2DM）患者糖尿病周围神经病变（DPN）之间的关系。本研究旨在探讨Lp-PLA2与DPN之间的潜在关联。方法：回顾性研究南京第一医院2024年3月至2024年8月住院治疗的T2DM患者880例。为了评估Lp-PLA2与DPN之间的关系，应用多元逻辑回归模型。该研究还采用了限制性三次样条（RCS）建模、分段回归、分层分析和受试者工作特征（ROC）曲线评估。结果：诊断为DPN的患者与未诊断为DPN的患者相比，Lp-PLA2水平升高。即使在对多个变量进行调整后，Lp-PLA2仍与DPN的较高可能性独立相关（比值比[OR] 1.011, 95%置信区间[CI] 1.008-1.014， P）。结论：血清Lp-PLA2水平与T2DM患者DPN的存在显著相关。这些研究结果表明，Lp-PLA2可以作为识别DPN风险患者的有价值的生物标志物，强调需要密切监测Lp-PLA2升高的T2DM患者，以降低发生DPN的风险和相关的不良健康结局。

{"title":"Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study","authors":"Yijia He , Miaomin Ye , Ziyang Shen, Ziyi Zhong, Yin Xia, Qian Li","doi":"10.1016/j.jdiacomp.2025.108950","DOIUrl":"10.1016/j.jdiacomp.2025.108950","url":null,"abstract":"<div><h3>Background</h3><div>Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme implicated in inflammation and oxidative stress, and has been associated with cardiovascular conditions and adverse outcomes, particularly in diabetes and its complications. However, no prior studies have examined the relationship between Lp-PLA2 and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This research aims to explore the potential association between Lp-PLA2 and DPN.</div></div><div><h3>Methods</h3><div>This retrospective study included 880 hospitalized patients with T2DM treated between March 2024 and August 2024 at Nanjing First Hospital. To assess the relationship between Lp-PLA2 and DPN, multiple logistic regression models were applied. The study also utilized restricted cubic spline (RCS) modeling, segmented regression, stratified analysis, and receiver operating characteristic (ROC) curve assessments.</div></div><div><h3>Results</h3><div>Patients diagnosed with DPN exhibited elevated Lp-PLA2 levels compared to those without DPN. Even after adjusting for multiple variables, Lp-PLA2 was independently associated with a higher likelihood of DPN (odds ratio [OR] 1.011, 95 % confidence interval [CI] 1.008–1.014, <em>P</em> < 0.001). The RCS analysis revealed a nonlinear association, with an inflection point at 215.8 ng/mL. In ROC curve analysis, the area under the curve (AUC) for Lp-PLA2 was 0.664, while the combined indicator AUC was 0.739.</div></div><div><h3>Conclusions</h3><div>Serum Lp-PLA2 levels show a significant correlation with the presence of DPN in patients with T2DM. These findings suggest that Lp-PLA2 could serve as a valuable biomarker for identifying patients at risk for DPN, emphasizing the need for close monitoring of T2DM individuals with elevated Lp-PLA2 to mitigate the risk of developing DPN and associated adverse health outcomes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108950"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006494","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

Association of dysfunctional adiposity index with kidney impairment is accounted for by pigment epithelium-derived factor in type 2 diabetes mellitus – An 11-year follow-up of the SMART2D cohort study

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications

Pub Date : 2025-02-01 DOI: 10.1016/j.jdiacomp.2025.108953

Mei Chung Moh , Serena Low , Sharon Li Ting Pek , Jian-jun Liu , Keven Ang , Wern Ee Tang , Ziliang Lim , Tavintharan Subramaniam , Chee Fang Sum , Su Chi Lim

Aims

This novel longitudinal study investigated the association of the new dysfunctional adiposity index (DAI) with kidney impairment in multi-ethnic Asians with type 2 diabetes mellitus (T2DM), and the mediation effect of pigment epithelium-derived factor (PEDF).

Methods

T2DM adults followed for up to 10.5 years were analyzed (n = 1611). DAI was calculated using a sex-specific formula. Baseline plasma PEDF levels were quantified using immunoassay. Diabetic kidney disease (DKD) was defined as presence of chronic kidney disease and/or albuminuria. The longitudinal outcomes included ≥40 % decline in estimated glomerular filtration rate from baseline (significant eGFR decline), albuminuria progression, and end-stage kidney disease (ESKD).

Results

Baseline DAI was associated with kidney parameters and DKD cross-sectionally, and showed increased discrimination ability. DAI was correlated with PEDF (rho = 0.324, P < 0.001). Additionally, DAI predicted significant eGFR decline (35.8 % prevalence) in the unadjusted (hazard ratio = 1.49, 95 % CI:1.31–1.70) and covariate-adjusted (hazard ratio = 1.23, 95 % CI:1.06–1.41) models; and was associated with ESKD and albuminuria progression. The relationship between DAI and significant eGFR decline was attenuated after accounting for PEDF, which explained 53.6 % of the indirect effect of DAI on significant eGFR decline.

Conclusions

Elevated DAI and its associated PEDF may serve as useful indicators for kidney function decline in T2DM.

{"title":"Association of dysfunctional adiposity index with kidney impairment is accounted for by pigment epithelium-derived factor in type 2 diabetes mellitus – An 11-year follow-up of the SMART2D cohort study","authors":"Mei Chung Moh , Serena Low , Sharon Li Ting Pek , Jian-jun Liu , Keven Ang , Wern Ee Tang , Ziliang Lim , Tavintharan Subramaniam , Chee Fang Sum , Su Chi Lim","doi":"10.1016/j.jdiacomp.2025.108953","DOIUrl":"10.1016/j.jdiacomp.2025.108953","url":null,"abstract":"<div><h3>Aims</h3><div>This novel longitudinal study investigated the association of the new dysfunctional adiposity index (DAI) with kidney impairment in multi-ethnic Asians with type 2 diabetes mellitus (T2DM), and the mediation effect of pigment epithelium-derived factor (PEDF).</div></div><div><h3>Methods</h3><div>T2DM adults followed for up to 10.5 years were analyzed (<em>n</em> = 1611). DAI was calculated using a sex-specific formula. Baseline plasma PEDF levels were quantified using immunoassay. Diabetic kidney disease (DKD) was defined as presence of chronic kidney disease and/or albuminuria. The longitudinal outcomes included ≥40 % decline in estimated glomerular filtration rate from baseline (significant eGFR decline), albuminuria progression, and end-stage kidney disease (ESKD).</div></div><div><h3>Results</h3><div>Baseline DAI was associated with kidney parameters and DKD cross-sectionally, and showed increased discrimination ability. DAI was correlated with PEDF (rho = 0.324, <em>P</em> < 0.001). Additionally, DAI predicted significant eGFR decline (35.8 % prevalence) in the unadjusted (hazard ratio = 1.49, 95 % CI:1.31–1.70) and covariate-adjusted (hazard ratio = 1.23, 95 % CI:1.06–1.41) models; and was associated with ESKD and albuminuria progression. The relationship between DAI and significant eGFR decline was attenuated after accounting for PEDF, which explained 53.6 % of the indirect effect of DAI on significant eGFR decline.</div></div><div><h3>Conclusions</h3><div>Elevated DAI and its associated PEDF may serve as useful indicators for kidney function decline in T2DM.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108953"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046806","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