Platelet Enzyme Activities in Diabetes Mellitus in Relation to Endothelial Damage

Diabetes ◽  
1983 ◽  
Vol 32 (Supplement_2) ◽  
pp. 47-51 ◽  
Author(s):  
H. U. Janka ◽  
E. Standl ◽  
W. Schramm ◽  
H. Mehnert
Keyword(s):  
Diabetes Mellitus ◽  
Enzyme Activities ◽  
Endothelial Damage

scholarly journals Significant polar vasculosis in a patient with a 30-year history of type 2 diabetes

2019 ◽  
Vol 2019 ◽  
Author(s):  
Yasuhiro Oda ◽  
Masayuki Yamanouchi ◽  
Hiroki Mizuno ◽  
Rikako Hiramatsu ◽  
Tatsuya Suwabe ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Damage ◽  
Diabetic Patients ◽  
List Type ◽  
History Of ◽  
Intraglomerular Pressure ◽  
Vascular Formation

Summary We report the renal histology of a 66-year-old man with hypertension, cardiovascular disease, and a 30-year history of type 2 diabetes mellitus with proliferative diabetic retinopathy, diabetic neuropathy, and diabetic foot status post toe amputation. Urinary protein excretion was 1.4 g/gCr, serum creatinine level 0.86 mg/dL, estimated glomerular filtration rate 69 mL/min/1.73 m2, and HbA1c 13–15%, despite using insulin. Light microscopy showed global glomerulosclerosis in 37% of the glomeruli, but the remaining glomeruli were intact. Significant polar vasculosis was present, while arteriolar sclerosis was mild. Electron microscopy revealed a thickened glomerular basement membrane, which is compatible with the early stage of diabetic glomerulopathy. The presented case was unique because glomerular changes seen typically in diabetes were not seen in the patient, despite the long-standing history of diabetes and diabetic comorbidities, while prominent polar vasculosis was found. Polar vascular formation helps preserve the glomeruli by allowing hyperosmotic blood bypass the glomeruli; this decreases intraglomerular pressure and minimizes glomerular endothelial damage. Learning points: A 66-year-old man with a 30-year history of type 2 diabetes mellitus with poor glycemic control underwent renal biopsy, which showed scarce glomerular changes typically seen in diabetic kidney disease and instead revealed significant polar vasculosis. Past studies demonstrated that the increased small vessels around the vascular hilus in diabetic patients originated from the afferent arterioles and drained into the peritubular capillaries. Polar vascular formation may preserve glomerular function by allowing the blood flow to bypass the glomeruli and decreasing the intraglomerular pressure, which minimizes endothelial damage of the glomerular tufts.

Loss of TM-Dependent PC-Activation Predisposes to Diabetic Nephropathy: Potential Role of Endothelial Apoptosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1029-1029
Author(s):  
Berend Isermann ◽  
Madhusudhan Thati ◽  
Ilya Vinnikov ◽  
Stefanie Herzog ◽  
Sina Huntscha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Caspase 3 ◽  
Ex Vivo ◽  
Vascular Complications ◽  
Diabetic Control ◽  
Endothelial Damage ◽  
Current Data ◽  
Diabetic Patients ◽  
Glomerular Damage

Abstract Increased levels of soluble thrombomodulin (TM) in patients with diabetes mellitus are considered a marker of endothelial damage. It is unknown whether the loss of endothelial TM-function contributes to the progression of vascular complications in diabetes mellitus. To address whether the loss of TM-dependent protein C (PC) activation contributes to diabetic complications such as diabetic nephropathy two animal models were employed: (1) TMPro mice, which have been previously described and carry a point mutation in the TM-gene (E404P), resulting in a loss of TM-dependent PC-activation, and (2) hPC mice, which carry a transgene resulting in the expression of a mutant “hyperactivatable” PC, which can be activated by thrombin in the absence of TM. The mutant PC could be captured from plasma samples of hPC mice and activated ex vivo by thrombin in the absence of TM. hPC mice had a prolonged bleeding time. Following induction of diabetes by streptozotocin TAT levels were increased in diabetic control (wild type) mice and to a larger extent in TMPro mice, but not in diabetic hPC mice. In comparison to diabetic control mice the kidney weight was increased in diabetic TMPro mice, but not in diabetic hPC mice. Albuminuria was increased in diabetic TMPro mice and reduced in diabetic hPC mice in comparison to diabetic control mice, indicating increased glomerular damage in TMPro mice and partial protection from glomerular damage in hPC mice. Consistently, using a histological score glomerular damage was more severe in diabetic TMPro mice in comparison to diabetic control mice, while diabetic hPC mice were protected. Preliminary data suggest that the observed changes are associated with increased apoptosis in glomeruli of diabetic TMPro mice. Using HUVECs we were able to establish that high glucose concentrations (30 mM) reduce TM-dependent PC activation. The reduced TM-dependent PC activation is associated with increased apoptosis. Glucose induced apoptosis in HUVECs is associated with an increased Bax/Bcl-2 ratio, increased translocation of Bax into mitochondria, and increased caspase-3 activation. Activated PC normalizes the Bax/Bcl-2 ratio, prevents translocation of Bax, and reduces caspase-3 activity. Further studies using TRAPs and inhibitory antibodies established that the antiapoptotic effect of aPC in glucose stressed endothelial cells is mediated through a Par-1 and EPCR-dependent mechanism. The current data strongly suggest that the loss of the endothelial TM-PC system is not just a marker of endothelial damage in diabetic patients, but rather contributes to the progression of diabetic vascular complications.

scholarly journals Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

2017 ◽  
Vol 312 (4) ◽  
pp. F673-F681 ◽  
Author(s):  
Andrés Carmona ◽  
Maria L. Agüera ◽  
Carlos Luna-Ruiz ◽  
Paula Buendía ◽  
Laura Calleros ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Prognostic Markers ◽  
Plasma Concentrations ◽  
Endothelial Damage ◽  
Inflammatory State ◽  
Monocyte Subpopulations ◽  
Elisa Data

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

scholarly journals Effect of melatonin on antioxidant state under type II diabetes at rat

2013 ◽  
Vol 59 (4) ◽  
pp. 434-442 ◽  
Author(s):  
A.A. Agarkov ◽  
T.N. Popova ◽  
L.V. Matasova
Keyword(s):  
Diabetes Mellitus ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Blood Serum ◽  
Enzyme Activities ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Diabetes Mellitus Type Ii ◽  
Melatonin Administration ◽  
Radical Processes

The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

Abstract 17744: In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes Mellitus

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Francesco Zaccardi ◽  
Francesca Pagliaccia ◽  
Alessandro Rizzi ◽  
Giovanna Petrucci ◽  
Aida Habib ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Activation ◽  
Linear Trend ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Endothelial Damage ◽  
Low Dose Aspirin ◽  
Repeated Sampling ◽  
The Stability

Introduction: While reduced responsiveness to low-dose aspirin has been associated with type 2 diabetes mellitus (T2DM), aspirin responsiveness remains unexplored in T1DM. Hypothesis: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM) and platelet COX-1 inhibition, as assessed by serum TXB2 (sTXB2), in uncomplicated, normotensive, normolipidemic T1DM subjects on insulin therapy. Methods: Upon informed consent, we enrolled 40 T1DM patients (26M, age 35±11yr, disease duration 16±11yr, BMI 24±2 kg/m2) and 10 healthy controls (6M, age 33±7yr). In 9 patients we assessed the stability of TXM excretion on 3 different visits. Thirty-one patients and all controls were given 100 mg daily aspirin for 21 days, and urinary TXM and sTXB2 were measured before and 24h after stopping aspirin. To assess the influence of glycemic variability on aspirin response, 26 patients underwent continuous glucose monitoring (CGM) for the first 24h after drug withdrawal. Results: TXM excretion in T1DM was significantly higher than in controls (930 [659-1358] vs 568 [385-619] pg/mg creatinine; p<0.001) and quite stable across repeated sampling (p for linear trend = 0.755). By multivariate analysis, urinary TXM was associated with microalbuminuria (β=0.23; p=0.042) at baseline. The degree of inhibition at 24h after aspirin dosing was similar in T1DM and controls for both sTXB2 (98.2% vs 98.6%, p=0.607) and urinary TXM (68.8% vs 68.4%, p=0.962). CGM-derived mean and standard deviation glucose were not associated with sTXB2 or TXM inhibition at 24h. Conclusions: We conclude that enhanced platelet activation in T1DM is independent of glycemic control and associated with kidney/endothelial damage. Moreover, in contrast to T2DM, the response to aspirin is unchanged, suggesting that the metabolic disturbance per se is not responsible for altered pharmacodynamics.

scholarly journals Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Malgorzata Walentowicz-Sadlecka ◽  
Piotr Domaracki ◽  
Pawel Sadlecki ◽  
Joanna Siodmiak ◽  
Marek Grabiec ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Hypertension ◽  
Endothelial Damage ◽  
Maternal Serum ◽  
Control Group ◽  
Elevated Concentration ◽  
Significant Difference ◽  
Endothelial Integrity

Background. Placental soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor, is considered an etiological factor of endothelial damage in pregnancy pathologies. An increase in the sFlt-1 level is associated with alterations of endothelial integrity. In contrast, vitamin D exerts a protective effect and low concentrations of 25(OH)D may have an adverse effect on common complications of pregnancy, such as gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM). The aim of this study was to analyze the levels of sFlt-1 in Polish women with physiological pregnancies and pregnancies complicated by GH, PE, and GDM. Moreover, we analyzed relationships between the maternal serum sFlt-1 level and the sFlt-1 to 25(OH)D ratio and the risk of GH and PE. Material and Methods. The study included 171 women with complicated pregnancies; among them are 45 with GH, 23 with PE, and 103 with GDM. The control group was comprised of 36 women with physiological pregnancies. Concentrations of sFl-1 and 25(OH)D were measured before delivery, with commercially available immunoassays. Results. Women with GH differed significantly from the controls in terms of their serum sFlt-1 levels (5797 pg/ml vs. 3531 pg/ml, p=0.0014). Moreover, a significant difference in sFlt-1 concentrations was found between women with PE and those with physiological pregnancies (6074 pg/ml vs. 3531 pg/ml, p<0.0001). GDM did not exert a statistically significant effect on serum sFlt-1 levels. Both logistic regression and ROC analysis demonstrated that elevated concentration of sFlt-1 was associated with greater risk of GH (AUC=0.70, p=0.0001) and PE (AUC=0.82, p<0.0001). Also, the sFlt-1 to 25(OH)D ratio, with the cutoff values of 652 (AUC=0.74, p<0.0001) and 653 (AUC=0.88, p<0.0001), respectively, was identified as a significant predictor of GH and PE. Conclusions. Determination of the sFlt-1/25(OH)D ratio might provide additional important information and, thus, be helpful in the identification of patients with PE and GH, facilitating their qualification for intensive treatment and improving the neonatal outcomes.

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