2218-PUB: Increased Platelet Reactivity Is Associated with Inflammation and Arterial Stiffness in Subjects with Prediabetes

"We investigated markers of platelet reactivity and low-grade inflammation, and their association with early markers of vascular disease in subjects with prediabetes and new onset type 2 diabetes (NDOM)."

"Platelet reactivity was evaluated as 11-dehydrothromboxane B2 urinary levels (TXB2)"

"TXB2 urinary levels were independently associated with hs-CRP, fibrinogen and HbA1c in multiple regression analysis."

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Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide or Lifestyle Changes-Induced Weight Loss

"Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXBand 8-iso-prostaglandin (PG)F2a, play a key role in atherothrombosis in obesity and type 2 diabetes mellitus (T2DM) since the earlier stages."

"After achievement of the weight loss target, a comparable reduction in U-11-dehydro-TXB2 (between-group = 0.679) and 8-iso-PGF-2a (p = 0.985) was observed in both arms in parallel with a comparable improvement in glycemic control, insulin sensitivity, SAT, high-sensativity C-reactive protein (hs-CRP)." 

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Increased circulating resistin is associated with insulin resistance, oxidative stress and platelet activation in type 2 diabetes mellitus

"Resistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. Age and gender adjusted serum resistin levels were significantly higher in patients than in controls. HOMA and 11-dehydro-TXB2 independently predicted resistin levels."

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Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease

"Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation.  The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes (DM) and cardiovascular disease."

“Patients with DM and CAD have significantly higher mean baseline levels of urinary 11-DHTXB2 than healthy controls likely indicating a higher platelet activation and risk for CVD.”

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The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus

"Our baseline results are in line with earlier studies, which have shown an association between glycemic control and urinary 11-DHTXB2 excretion. In addition, improving glycemic control has been shown to lead to a decreased 11-DHTXB2 excretion."

"In the present study, the difference in urinary 11-DHTXB2 excretion was also influenced by C-reactive protein levels, which were different between the study groups and may reflect the influence of the inflammatory state found in diabetes on thromboxane formation."

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Urinary 11-dehydro thromboxane B2 levels in type 2 diabetic patients before and during aspirin intake

"Diabetic patients commonly present an increased risk for cardiovascular events, for which aspirin is the most frequently used medication for primary prevention.  Urinary 11-dehydro thromboxane (11-dhTXB2) concentrations assess the effect of aspirin on platelets and identify patients who are at risk of cardiovascular events.  The present study investigated whether or not type 2 diabetic patients who took a daily dose of 100 mg of aspirin had a signficant reduction in urinary 11-dhTXB2 concentrations and whether these results were associated with clinical and laboratory variables."

“Most patients enrolled in the present study also presented a reduced or minimal response to low-dose aspirin therapy, thereby indicating a clear variability related to aspirin effectiveness."

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Nutraceuticals in diabetes and metabolic syndrome

"Metabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes.  Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low-grade inflammation, alterred oxidative/antioxidant status, and persistent platelet activation."

"We examined the effects of short-term vitamin E supplementation (600 mg daily for 2 week) on the urinary excretion of 8-iso-PGF2alpha and 11-dehydro-TXB2. Vitamin E supplementation was associated with detectable changes in plasma vitamin E levels and caused virtually complete normalization of 8-iso-PGF2alpha excretion. Moreover, changes in F2-isoprostane formation were accompanied by similar reductions in thromboxane metabolite excretion."

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The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients.  Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients."

“Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP- and collagen-induced platelet aggregation, 11-DHXTB2 levels, and aspirin reaction units measured by Verify Now than nondiabetic patients.”

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Thromboxane-dependent CD40 ligand release in type II diabetes mellitus

"The goals of this study were to characterize the platelet contribution to soluble CD-40 ligand (sCD40L), to correlate its formation with the extent of oxidative stress and platelet activation, and to investigate the effects of improved metabolic control and low-dose aspirin on these processes."

“This study provides several lines of evidence for the dependence of sCD40L release on TXA2-dependent platelet activation in T2DM and provides novel mechanistic insight into the amplification loops of persistent platelet activation in this setting.”

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Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus

“Compared with non-diabetics, patients with Type II diabetes mellitus (T2Dm) have a two-to four-fold increased risk of ischemic cardiovascular disease, a risk largely independent of concomitant hypertension, hypercholesterolemia, and smoking.”

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