Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Roumeliotis A
PROVIDER: S-EPMC8448992 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The worldwide increasing prevalence of obesity and sedentary lifestyle is the main cause of the rising incidence of T2DM. Due to chronic macrovascular and microvascular complications, T2DM represent a huge socioeconomic burden in the world. Oxidative stress is a key pathogenic mechanism implicated in diabetic coronary artery disease (CAD). Polymorphisms of oxidative stress genes are known to influence oxidative stress levels and are therefore thought to impact CAD pathogenesis. Identifying higher risk groups would be rational, since it would allow better sample selection and thus better results in antioxidant trials. In this review, we summarize the evidence of oxidative stress gene polymorphisms related to the pathogenesis of CAD. Moreover, we provide a review of antioxidants tested in subjects with CAD.
| S-EPMC5425652 | biostudies-literature
Project description:Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an estimated 30 million people worldwide. It is characterized by the destruction of pancreatic β cells by the immune system, which leads to lifelong dependency on exogenous insulin and imposes an enormous burden on patients and health-care resources. T1DM is also associated with an increased risk of comorbidities, such as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD), further contributing to the burden of this disease. Although T cells are largely considered to be responsible for β-cell destruction in T1DM, increasing evidence points towards a role for B cells in disease pathogenesis. B cell-depletion, for example, delays disease progression in patients with newly diagnosed T1DM. Loss of tolerance of islet antigen-reactive B cells occurs early in disease and numbers of pancreatic CD20+ B cells correlate with β-cell loss. Although the importance of B cells in T1DM is increasingly apparent, exactly how these cells contribute to disease and its comorbidities, such as DKD, is not well understood. Here we discuss the role of B cells in the pathogenesis of T1DM and how these cells are activated during disease development. Finally, we speculate on how B cells might contribute to the development of DKD.
| S-EPMC6733025 | biostudies-literature
Project description:In this project, using discovery-based mass spectrometry approach and adopting data-dependent LC-MS/MS, we detected and identified modified peptides in complex clinical plasma samples and developed first-level biomarker verification strategy. Further, using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS) based targeted approach which virtually quantifies irreversible oxidation at any targeted cysteine, we quantified cysteine tri-oxidation in HSA in diabetes patients. Site-specific tri-oxidized HSA could be a potential biomarker of diabetes and provide directive of disease mechanism.
2020-05-26 | PXD012667 | Pride
Project description:The purpose of this study is to investigate potential associations between optical coherence tomography angiography (OCTA) parameters and diabetic kidney disease (DKD) categories in type 1 diabetes mellitus (T1DM) patients and controls. A complete ocular and systemic examination, including OCTA imaging tests and bloods, was performed. OCTA parameters included vessel density (VD), perfusion density (PD), foveal avascular zone area (FAZa), perimeter (FAZp) and circularity (FAZc) in the superficial vascular plexus, and DKD categories were defined according to glomerular filtration rate (GFR), albumin-creatinine ratio (ACR) and KDIGO prognosis risk classifications. A total of 425 individuals (1 eye/1 patient) were included. Reduced VD and FAZc were associated with greater categories of GFR (p = 0.002, p = 0.04), ACR (p = 0.003, p = 0.005) and KDIGO risk prognosis classifications (p = 0.002, p = 0.005). FAZc was significantly reduced in greater KDIGO prognosis risk categories (low risk vs. moderate risk, 0.65 ± 0.09 vs. 0.60 ± 0.07, p < 0.05). VD and FAZc presented the best diagnostic performance in ROCs. In conclusion, OCTA parameters, such as VD and FAZc, are able to detect different GFR, ACR, and KDIGO categories in T1DM patients and controls in a non-invasive, objective quantitative way. FAZc is able to discriminate within T1DM patients those with greater DKD categories and greater risk of DKD progression.
| S-EPMC8745787 | biostudies-literature
Project description:BackgroundDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide. Epidemiological evidence of the association between urinary sodium excretion and the presence of DKD in patients with type 2 diabetes mellitus (T2DM) has not yet been well established.MethodsWe performed a cross-sectional study of 1545 patients with T2DM over aged 20 years old from January 2018 to December 2020. Urinary sodium excretion was measured by 24-hour urine samples in inpatients and morning fasting urine samples in outpatients. The associations between urinary sodium excretion and the risks of DKD were examined using stepwise regression analysis, logistic regression analysis and multivariable-adjusted restricted cubic splines (RCS).ResultsRegression analysis showed that urinary sodium was independently associated with urinary albumin to creatinine ratio (UACR) level (P = 0.006) and the risks of DKD (P = 0.042). In multivariable-adjusted RCS analysis, urinary sodium excretion was significantly associated with UACR in all patients (P = 0.008), and exhibited a J-shaped relationship. Logistic regression analysis showed that increased urinary sodium excretion was significantly associated with increased risks of DKD [OR (95% CI); 1.56 (1.07-2.27); P = 0.020]. However, the relationships between urinary sodium excretion and the risks of DKD and albuminuria showed no significance, after further adjustment for HOMA-IR and ba-PWV (brachial-ankle pulse wave velocity) (Both P > 0.05).ConclusionsHigher urinary sodium excretion level was associated with increased risks of DKD among patients with T2DM, dependent of vascular sclerosis and insulin resistance.
| S-EPMC8582599 | biostudies-literature
Project description:BACKGROUND AND AIMS:Diabetic kidney disease (DKD) is the leading cause of end stage renal disease worldwide and is associated with increased cardiovascular mortality. The endothelin system has been implicated in the pathogenesis of arterial hypertension and renal dysfunction. In the present study, the association of DKD with polymorphisms in ET-1 (EDN1) and ETRA (EDNRA) genes was analyzed in patients with type 2 diabetes mellitus (T2DM). METHODS:A case-control study was conducted in 548 white T2DM patients. Patients with proteinuria or on dialysis were considered cases and patients with normoalbuminuria were considered controls. Two polymorphisms in the EDN1 gene (rs1800541 and rs57072783) and five in EDNRA gene (rs6842241; rs4835083; rs4639051; rs5333 and rs5343) were genotyped and haplotype analyses were performed. RESULTS:The presence of rs57072783 T allele (TT/TG vs. GG) or rs1800541 G allele (GG/GT vs. TT) protected against DKD (OR = 0.69, 95 % CI 0.48-0.99, P = 0.049; and OR = 0.60, 95 % CI 0.41-0.88, P = 0.009, respectively). However in multivariate analyses, only the rs1800541 G allele remained independently associated with DKD (P = 0.046). CONCLUSIONS:The present study shows that ET-1 could be involved in the pathogenesis of DKD in patients with T2DM.
| S-EPMC4653842 | biostudies-literature
Project description:Background and objectivesOwing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM.Study design & settingIn this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed.ResultsA total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD.ConclusionsThe prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.
| S-EPMC9964578 | biostudies-literature
Project description:Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease, and it is crucial to understand the pathophysiology of DKD. The control of blood glucose levels by various glucose-lowering drugs, the common use of inhibitors of the renin-angiotensin system, and the aging of patients with diabetes can alter the disease course of DKD. Moreover, metabolic changes and associated atherosclerosis play a major role in the etiology of DKD. The pathophysiology of DKD is largely attributed to the disruption of various cellular stress responses due to metabolic changes, especially an increase in oxidative stress. Therefore, many antioxidants have been studied as therapeutic agents. Recently, it has been found that NRF2, a master regulator of oxidative stress, plays a major role in the pathogenesis of DKD and bardoxolone methyl, an activator of NRF2, has attracted attention as a drug that increases the estimated glomerular filtration rate in patients with DKD. This review outlines the altered stress responses of cellular organelles in DKD, their involvement in the pathogenesis of DKD, and discusses strategies for developing therapeutic agents, especially bardoxolone methyl.
| S-EPMC8301131 | biostudies-literature
Project description:BackgroundDiabetic kidney disease (DKD) represents a heavy burden in type 2 diabetes mellitus (T2DM). Ferroptosis plays an important role in DKD, and it thus provides new perspectives to pursue more related biomarkers to assess the disease severity and prognosis. Glutathione peroxidase 4 (GPX4) is the mainstay in regulating ferroptosis. The current study investigated the predictive value of kidney GPX4 expression level in DKD progression.MethodsWe measured GPX4 levels in kidney paraffin sections of 85 biopsy-proven DKD patients by immunohistochemistry staining. The associations between the GPX4 level and clinicopathological parameters as well as renal outcomes were analyzed.ResultsGPX4 is mainly expressed in kidney tubulointerstitium, especially in tubular epithelial cells of DKD patients. The GPX4 expression level was significantly lower in DKD patients than healthy controls. Besides, GPX4 level significantly correlated with proteinuria (r = -0.42, p < 0.001), urinary albumin-to-creatinine ratio (uACR) (r = -0.40, p < 0.01), serum creatinine (Scr) (r = -0.59, p < 0.001), estimated glomerular filtration rate (eGFR) (r = 0.66, p < 0.001), and the percentage of sclerosed glomeruli (r = -0.42, p < 0.001) in renal specimens. During follow-up, the GPX4 level positively correlated with eGFR slope (r = 0.48, p < 0.001), and GPX4-low patients showed a significantly higher probability of developing end-stage kidney disease (ESKD) compared with GPX4-high patients (p < 0.01). Moreover, after adjusting for other potential predictors, the GPX4 level was still an independent predictor of developing ESKD (HR 2.15, 95% CI 1.08 to 4.28, p < 0.05).ConclusionsKidney tubulointerstitial GPX4 expression level was associated with the disease severity and progression of DKD.
| S-EPMC9581693 | biostudies-literature
Project description:BackgroundDiabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride-Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively.Materials and methodsCross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12-24) months. The main outcome was DKD prevalence as defined with eGFR <60 mL/min/1.73 m2 or continuously increased urinary microalbuminuria: creatinine ratio (>30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD.ResultsIn cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744-3.144, p < 0.001), and eGFR <60 mL/min/1.73 m2 (1.696, 95% CI =1.096-2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042-2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63-0.76).ConclusionThe TyG Index is a potential predictor for DKD in T2DM patients.Clinical trialClinical Trials identification number = NCT03692884.
| S-EPMC8296712 | biostudies-literature