Advantages of Metformin Therapy for the Prevention and Mitigation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease: A Real-Word Evidence From Large-Scale Cohort

2021 ◽  
Author(s):  
Soie Kwon ◽  
Jeong Hyun Ha ◽  
Dong Ki Kim ◽  
Yon Su Kim ◽  
Chun Soo Lim ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Foot ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Real Word ◽  
Diabetic Kidney ◽  
Metformin Therapy

scholarly journals Diabetic Foot Ulcer Risk with Diabetic Kidney Disease and Renal Failure among 10,680 Patients

2021 ◽  
Vol 3 (4) ◽  
pp. 345-354
Author(s):  
Kamran Mahmood Ahmed Aziz
Keyword(s):  
Risk Factors ◽  
Kidney Disease ◽  
Diabetic Foot ◽  
Odds Ratio ◽  
Diabetic Kidney Disease ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Urine Protein ◽  
Diabetic Kidney ◽  
Spot Urine

Objectives: Patients with Diabetic Kidney Disease (DKD) and foot ulcer have poor prognosis. However, no study have found association of diabetic foot ulcer (DFU) with diabetic kidney dysfunction and their co-existing risk factors. Materials and Methods: This cross sectional study collected the data for 10,680 patients for 15 years. All variables were analyzed biochemically and statistically by standardized methodology. Results: Levels of HbA1c, creatinine, systolic and diastolic blood pressures, microalbuminuria, spot urine protein, and spot urine protein to creatinine ratio were higher among the groups with foot ulcers (p-value < 0.0001 for all). Average ABI was observed to be lower among the groups demonstrating nephropathy and DKD (p=0.025 and 0.022 respectively. DFU was significantly associated with HTN (odds ratio 2.2; 95% CI 1.66 to 2.9; p < 0.0001), nephropathy (odds ratio 4.77; 95% CI 3.53 to 6.5; p < 0.0001) and DKD (odds ratio 4.77 and 6.83; 95% CI 4.6 to 10.2; p < 0.0001). HbA1c of 7.8% was 60% sensitive and 52% specific for the development of DFU. Creatinine of 1.2 mg/dl was 75% sensitive and 48% specific for DFU. Spot urine protein excretion from nephrons of 35 mg/dl was 88% sensitive and 90% specific for the development of DFU. Conclusion: Nephropathy/DKD are risk factors for the development of DFU. With optimal diabetes control, regular and routine assessment of the feet and early screening of diabetic patients for neuropathy, nephropathy, hypertension, dyslipidaemia and other diabetic complications are essential. Doi: 10.28991/SciMedJ-2021-0304-6 Full Text: PDF

Diabetic Foot Ulcer as a Cause of Significant Decline in the Renal Function Among South Indian Population With Type 2 Diabetes: Role of TGF-β1 and CCN Family Proteins

2019 ◽  
Vol 18 (4) ◽  
pp. 354-361 ◽  
Author(s):  
T. P. Smina ◽  
M. Rabeka ◽  
Vijay Viswanathan
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Foot ◽  
Diabetic Kidney Disease ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
South Indian ◽  
Tgf Β1

In the present study, a total of 428 South Indian subjects were divided into four different groups, consisting of individuals with type 2 diabetes without any other complications (T2DM), T2DM subjects with stage 2 and 3 diabetic kidney disease (CKD), T2DM subjects with grade 2 or 3 diabetic foot ulcer (DFU) and T2DM subjects having both diabetic kidney disease and diabetic foot ulcer (CKDDFU). The study was conducted ambispectively by comparing the changes in renal function among two consecutive periods, i.e., the period prior to the development of grade 2 and 3 diabetic foot ulcer (retrospectively) and after the development of DFU (prospectively). A gradual and uniform reduction of eGFR was observed throughout the study period in the subjects affected with either CKD or DFU alone. Whereas in subjects with both CKD and DFU, there was a sharp decline in the eGFR during the six months prior to the baseline, i.e., the period in which the development of ulcer and its progression to grade 2 or 3 happened. Remarkable elevations in the levels of TGF-β1 and CCN2 (CTGF), as well as a significant reduction in the level of CCN3 (NOV), were observed in the serum of CKDDFU group subjects, compared to the other groups. Increased production of TGF-β1 in response to the inflammatory stimulus from multiple sites in CKDDFU subjects caused a subsequent down-regulation of CCN3, followed by the activation of a large quantity of CCN2.

scholarly journals The New and the Old: Platform Cross-Validation of Immunoaffinity MASS Spectrometry versus ELISA for PromarkerD, a Predictive Test for Diabetic Kidney Disease

Proteomes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 31
Author(s):  
Scott Bringans ◽  
Kirsten Peters ◽  
Tammy Casey ◽  
Jason Ito ◽  
Richard Lipscombe
Keyword(s):  
Mass Spectrometry ◽  
Kidney Disease ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Clinical Laboratory ◽  
Predictive Test ◽  
Protein Biomarkers ◽  
Diabetic Kidney ◽  
Technology Platforms ◽  
Mass Spectrometry Assay

PromarkerD is a proteomics derived test for predicting diabetic kidney disease that measures the concentrations of three plasma protein biomarkers, APOA4, CD5L and IBP3. Antibodies against these proteins were developed and applied to a multiplexed immunoaffinity capture mass spectrometry assay. In parallel, and facilitating current clinical laboratory workflows, a standard ELISA was also developed to measure each protein. The performance characteristics of the two technology platforms were compared using a cohort of 100 samples, with PromarkerD test scores demonstrating a high correlation (R = 0.97). These technologies illustrate the potential for large scale, high throughput clinical applications of proteomics now and into the future.

scholarly journals Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yajing Huang ◽  
Jingwei Chi ◽  
Fanxiang Wei ◽  
Yue Zhou ◽  
Yihai Cao ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Endothelial Damage ◽  
Inflammatory Factors ◽  
Mtdna Copy Number ◽  
Diabetic Kidney ◽  
Patients With Diabetes ◽  
Stage Renal Disease

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.

Frequency of Chronic Kidney Disease in Type 2 Diabetic Patients Presenting with Diabetic Foot Ulcer

2020 ◽  
Author(s):  
Ghazala Usman
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
P Value ◽  
Diabetic Patients ◽  
Type 2 Dm ◽  
Significant Difference

Background: Recent evidence states that about a quarter of all diabetic patients will experience an ulcer on foot at some point in their lifetime and 15-25% of these will require foot amputation. In the present study, we aimed to evaluate the incidence of chronic kidney disease (CKD) in Type 2 diabetes mellitus (T2DM) patients presenting with Diabetic foot ulcer. Methods: The present study was carried out at Jinnah Postgraduate Medical Center (JPMC), Sindh from February-August 2017. Over 100 Type 2 - DM patients, aged between 35-60 years who presented with diabetic foot ulcer took part in this study. Data was collected and documented in pre-approved pro-forma, subsequently, entered and analyzed via SPSS version 19. Chi-square was applied to test any significant difference between the categories with a p-value of ≤0.05 considered as significant. Results: The mean serum creatinine (mg/dl) value was reported to be 1.17 ± 0.45. Frequency of CKD in Type 2 - DM patients presenting with diabetic foot ulcer was 31%. Male gender was affected more from CKD. Frequency distribution of chronic kidney disease among duration of DM groups 10-15 years = 35.5% and >15 years = 64.5%. The characteristics of HbA1c (g/dl) of study population was 8.34 ± 0.59. Conclusion: Occurrence of CKD in Type 2 - DM patients presenting with diabetic foot ulcer was much higher as compared to national and international studies. Therefore, special attention should be given on regular screening of diabetic patients with a complaint of a foot ulcer.

scholarly journals Metabolomics in Diabetic Kidney Disease: Unraveling the Biochemistry of a Silent Killer

2016 ◽  
Vol 44 (2) ◽  
pp. 92-103 ◽  
Author(s):  
Manjula Darshi ◽  
Benjamin Van Espen ◽  
Kumar Sharma
Keyword(s):  
Kidney Disease ◽  
Small Molecules ◽  
Animal Studies ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Acid Oxidation ◽  
Treatment Interventions ◽  
Diabetic Kidney ◽  
Bioinformatic Tools ◽  
Large Scale Analysis

The development of new therapies for chronic diseases, such as diabetic kidney disease (DKD), will continue to be hampered by lack of sufficient biomarkers that will provide insights and will be responsive to treatment interventions. The recent application of metabolomic technologies, such as nuclear magnetic resonance and mass spectroscopy, has allowed large-scale analysis of small molecules to be interrogated in a targeted or untargeted manner. Recent advances from both human and animal studies that have arisen from metabolomic analysis have recognized that mitochondrial function and fatty acid oxidation play key roles in the development and progression of DKD. Although many challenges in the technology for clinical chronic kidney disease (CKD) are yet to be validated, there will very likely be ongoing major contributions of metabolomics to develop new biochemical understanding for diabetic and CKD. The clinical application of metabolomics and accompanying bioinformatic tools will likely be a cornerstone of personalized medicine triumphs for CKD.

scholarly journals Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie Klein ◽  
Cécile Caubet ◽  
Mylène Camus ◽  
Manousos Makridakis ◽  
Colette Denis ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Enzyme Inhibitor ◽  
Oral Treatment ◽  
Drug Repurposing ◽  
Water Soluble ◽  
Diabetic Patients ◽  
Diabetic Kidney ◽  
Connectivity Mapping

Abstract While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25–30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs’s signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs’s signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.

scholarly journals Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e053019
Author(s):  
David J Leehey ◽  
Kimberly Carlson ◽  
Domenic J Reda ◽  
Ian Craig ◽  
Christina Clise ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Usual Care ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Controlled Trial ◽  
Scientific Journal ◽  
Phosphodiesterase Inhibitor ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Kidney ◽  
Study Results

IntroductionDiabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease (ESRD) in the USA and worldwide. Recent experimental and clinical data suggest that the non-specific phosphodiesterase inhibitor pentoxifylline (PTX) may decrease progression of chronic kidney disease. However, a large-scale randomised clinical trial is needed to determine whether PTX can reduce ESRD and death in DKD.Methods and analysisVeterans Affairs (VA) PTXRx is a pragmatic, randomised, placebo-controlled multicentre VA Cooperative Study to test the hypothesis that PTX, when added to usual care, leads to a reduction in the time to ESRD or death in patients with type 2 diabetes with DKD when compared with usual care plus placebo. The study aims to enrol 2510 patients over a 4-year period with an additional up to 5-year follow-up to generate a total of 646 primary events. The primary objective of this study is to compare the time until ESRD or death (all-cause mortality) between participants randomised to PTX or placebo. Secondary endpoints will be: (1) health-related quality of life, (2) time to doubling of serum creatinine, (3) incidence of hospitalisations for congestive heart failure, (4) incidence of a three-point major adverse cardiovascular events composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), (5) incidence of peripheral vascular disease, (6) change in urinary albumin-to-creatinine ratio from baseline to 6 months and (7) rate of annual change in estimated glomerular filtration rate (eGFR) during the study period.Ethics and disseminationThis study was approved by the VA Central Institutional Review Board (cIRB/18-36) and will be conducted in compliance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The Hines Cooperative Studies Programme will finalise the study results, which will be published in accordance with the Consolidated Standards of Reporting Trials statement in a peer-reviewed scientific journal.Trial registration numberNCT03625648.

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