Relationship of Soluble RAGE and RAGE Ligands HMGB1 and EN-RAGE to Endothelial Dysfunction in Type 1 and Type 2 Diabetes Mellitus

2012 ◽  
Vol 120 (05) ◽  
pp. 277-281 ◽  
Author(s):  
J. Škrha Jr ◽  
M. Kalousová ◽  
J. Švarcová ◽  
A. Muravská ◽  
J. Kvasnička ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Advanced Glycation Endproducts ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Glycation Endproducts ◽  
Diabetic Vascular Complications ◽  
Soluble Rage

AbstractReceptor for advanced glycation endproducts (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= − 0.602, p<0.002 and r= − 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

scholarly journals Clinical and Biochemical Predictors of Endothelial Dysfunction in Egyptian Adolescents with Type 1 and those with Type 2 Diabetes

2021 ◽  
pp. 87-97
Author(s):  
EkramHamed Zakaria ◽  
MedhatAbdElmaged Ghazy ◽  
Wesam Salah Mohamed ◽  
Nesreen Ahmed Kotb
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
University Hospital ◽  
Control Group ◽  
Model Assessment ◽  
Significant Difference

Aims: Since endothelial dysfunction precedes clinically significant diabetic vascular complications, circulating endothelial progenitor cells (EPCs) have generated interest as a biomarker of endothelial function and are considered a mirror for endogenous vasculo-regenerative capacity. So we aimed to assess EPCs count in adolescents with type 1 diabetes mellitus (T1DM) in comparison to those with type 2 diabetes mellitus (T2DM) and extend these findings to assess their relationship to other clinical and biochemical risks of endothelial dysfunction. Patients and Methods: Fifty Egyptian adolescents were included in this study, 20 with T1DM, 20 T2DM and 10 healthy control subjects. Patients are recruited from Diabetes and Endocrinology Unit, outpatient clinic of internal medicine department Tanta University Hospital, in the period from 2017 to 2019. EPCs count was determined by Flowcytometry, anthropometric measurements and laboratory investigations were done for fasting and 2-hours post-prandial blood glucose, serum lipid profile, HbA1c, urinary albumin creatinine ratio, fasting C peptide, and homoeostasis model assessment of insulin resistance (HOMA- IR). Results: In T1DM, EPCs count was significantly higher compared to T2DM(0.032) and control group(p0.001) and it was negatively correlated with age of patients and duration of diabetes but was positively correlated with HbA1c. While, the count was higher in T2DM compared to control with no statistically significant difference(p0.063) and negatively correlated with body mass index, waist circumference, blood pressure and HOMA-IR. Conclusion: Adolescents with T2DM have distressing clinical and biochemical findings and significantly lower count of (EPCs) than adolescents with T1DM. This puts them at potential higher risk for early development of endothelial dysfunction and less power of vascular repair that may potentiate early harboring of vascular complications.

scholarly journals Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173379 ◽  
Author(s):  
Bernardina T. Fokkens ◽  
Douwe J. Mulder ◽  
Casper G. Schalkwijk ◽  
Jean L. Scheijen ◽  
Andries J. Smit ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Retinal Detachment ◽  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Glycation Endproducts

Susceptibility of Glutathione--S-Transferase Polymorphism to CVD Development in Type 2 Diabetes Mellitus - A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Santhi Priya Sobha ◽  
Kumar Ebenezar
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disorder ◽  
Vascular Complications ◽  
Clinical Importance ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Metabolic Conditions ◽  
Gst Polymorphism ◽  
Gene Status

Background: Metabolic disorder affects normal homeostasis and can lead to the development of diseases. Diabetes mellitus is the most common metabolic disorder, and a cluster of metabolic conditions can lead to cardiovascular disease (CVD) development. Diabetes mellitus and CVD are closely related, with oxidative stress, playing a major role in the pathophysiology. Glutathione-S-Transferases (GST) potentially play an important role by reducing oxidative stress and is found to be the underlying pathophysiology in the development of diabetes, cardiovascular diseases (CVD), etc. Objectives: In this review, the role of GST genetic variant in the development of diabetes mellitus, CVD and diabetic vascular complications has been focused. Results: Based on the literature, it is evident that the GST can act as an important biochemical tool providing significant evidence regarding oxidative stress predominant in the development of diseases. Analysis of GST gene status, particularly detection of GSTM1 and GSTT1 null mutations and GSTP1 polymorphism, have clinical importance. Conclusion: The analysis of GST polymorphism may help identify the people at risk and provide proper medical management. Genotyping of GST gene would be a helpful biomarker for early diagnosis of CVD development in DM and also in CVD cases. More studies focusing on the association of GST polymorphism with CVD development in diabetic patients will help us determine the pathophysiology better.

scholarly journals Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Fatma A. Khalaf ◽  
Hatem R. Ibrahim ◽  
Hanan M. Bedair ◽  
Maha M. Allam ◽  
Amr A. Elshormilisy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Vascular Complications ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR). Results The most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients. Conclusion This study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

scholarly journals Effect of Type 1 and Type 2 Diabetes Mellitus on Complication and Reoperation Rates of Ankle Arthrodesis and Total Ankle Arthroplasty

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0049
Author(s):  
William Tucker ◽  
Brandon Morris ◽  
Armin Tarakemeh ◽  
Scott Mullen ◽  
Paul Schroeppel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Independent Risk Factor ◽  
Surgical Intervention ◽  
Ankle Arthrodesis ◽  
Diabetic Patients ◽  
Ankle Arthritis ◽  
End Stage ◽  
Reoperation Rates

Category: Diabetes Introduction/Purpose: Diabetes mellitus (DM) poses a risk for increased rate of complications in many orthopaedic procedures, especially in patients undergoing elective arthroplasty procedures. Treatment of end-stage ankle arthritis includes both arthroplasty and arthrodesis. Current literature provides minimal guidance regarding outcomes of total ankle replacement (TAR) or ankle arthrodesis (AA) in diabetic patients. The authors of this study utilized a large database to compare rates of postoperative complications and reoperations of diabetic patients undergoing surgical management of ankle arthritis to rates seen in non-diabetic patients. Methods: Using the PearlDiver Technologies, Inc. database, Medicare patients diagnosed with ankle arthritis using ICD-9 codes were identified from 2005 to 2014. Patients were then sorted as diabetic or non-diabetic. Diabetic patients were then further stratified into Type 1 diabetes (T1DM) and Type 2 diabetes (T2DM). Type 2 diabetics requiring insulin (T2ID) and not requiring insulin (T2NID) were also isolated. Patients were identified who underwent either AA or TAR utilizing ICD-9 procedure and CPT codes. These groups were evaluated for postoperative complications and reoperation rates. Chi-Squared testing was used to determine significance. Multivariate analysis was performed to determine whether diabetes represents an independent risk factor. Results: 1477 diabetic patients underwent TAR and 5399 underwent AA versus 3900 TAR and 7838 AA in nondiabetics. Diabetics undergoing AA experienced complications at 32.2%, reoperations at 30.8%, and revisions at 18.7% versus 13.3%, 22.3%, and 19.2% respectively in patients without diabetes(P<0.05). In diabetics undergoing TAR, the complication rate was 21.6% and reoperation rates were 16.9% versus 12.5% and 13% respectively in their non-diabetic counterparts(P<0.05). Revision rates were similar. Patients with T1DM had more reoperations and complications in both TAR and AA compared to those with T2DM (P<0.05). In both surgical groups, Patients with T2ID had more complications and reoperations than those with T2NID(P<0.05). Multivariate analysis revealed diabetes as an independent risk factor for complication and reoperation in AA but only complication in TAR(P <0.05). Conclusion: Patients with a diagnosis of diabetes mellitus experienced higher complication and total reoperation rates when undergoing either TAR or AA. T1DM appears to impart a greater risk of surgical complication and repeat surgical intervention than does T2DM. However when insulin is required in T2DM, complication and reoperation rates are similar to those of T1DM. Patient selection for surgical management of end-stage ankle arthritis should incorporate diabetic type and insulin dependency when considering surgical intervention.

scholarly journals Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients

2006 ◽  
Vol 154 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Lars Melholt Rasmussen ◽  
Lise Tarnow ◽  
Troels Krarup Hansen ◽  
Hans-Henrik Parving ◽  
Allan Flyvbjerg
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Systolic Blood Pressure ◽  
Kidney Function ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Patients With Diabetes ◽  
Type 1 Diabetic Patients

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.

Sign in / Sign up

Export Citation Format

Share Document