Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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OBJECTIVE -Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now.RESEARCH DESIGN AND METHODS -Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially.RESULTS -The HAGE induced a maximum reactive hyperemia decrease of Ϫ60.0% after 2 h and a maximum FMD impairment of Ϫ35.1% after 4 h, without affecting endotheliumindependent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine.CONCLUSIONS -Our study confirms micro-and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment. Diabetes Care 29:2064 -2071, 2006E ndothelial dysfunction is an early marker of atherosclerosis and accompanies states showing a high cardiovascular risk, such as smoking (1), dyslipidemia (2), arterial hypertension (3), obesity (4), coronary artery disease (5), congestive heart failure (6), and type 1 (7) and type 2 (8) diabetes. Postprandial endothelial dysfunction has been proposed as the link between postprandial dysmetabolism and atherosclerosis (9) and occurs not only in patients with cardiovascular disease (10) or diabetes (11) but even in healthy subjects (12). Distinctive and cumulative (11) effects of hyperglycemia (13) and hypertriglyceridemia (14) on postprandial endothelial dysfunction have been shown. Since the postprandial state covers most of our daytime, interventions aimed at reducing postprandial endothelial dysfunction might play a decisive role in prevention of atherosclerosis. Several therapeutic approaches have been suggested for the treatment of postprandial endothelial dysfunction, including insulin, folic acid, tetrahydrobiopterin, vitamins C and E, and statins (11). These approaches aim at reducing postprandial oxidative stress (vitamins C and E, statins, and partly folic acid), postprandial hyperglycemia (insul...

In patients with T2DM, a HAGE meal induces a more pronounced acute impairment of vascular function than does an otherwise identical LAGE meal. Therefore, chemical modifications of food by means of cooking play a major role in influencing the extent of postprandial vascular dysfunction.

Diabetes mellitus is associated with aggravated development of vascular complications. Yet, it has not been established whether platelet hyperreactivity contributes as a pathogenetic factor. In order to study the role of activated platelets in diabetes mellitus, we investigated the expression of the membrane activation markers CD63 (GP53) and CD62 (GMP-140) as direct indicators of in vivo activation. The CD63-positive fraction was significantly higher in patients (6.1% X 3.7 +/- 1) than in controls (2.7% X 3 +/- 1). In parallel, the CD62-positive fraction was significantly elevated in patients to 5% X 2.5 +/- 1 in comparison to controls (3% X 2 +/- 1). Patients with angiopathy had a mean increase of 304% in CD63-positive and of 223% in CD62-positive platelets. Patients without clinically detectable angiopathy showed a trend to an increased fraction in CD63-/CD62-positive platelets. There was no correlation of the activation markers with fasting blood glucose, HbA1 or platelet count. CD63 platelet bound fluorescence significantly increased with platelet size in the patient group. We conclude that in diabetes mellitus an increased number of large platelets circulate in an activated state predominantly in patients with angiopathy. This could imply that platelets become activated by vascular lesions. The trend in patients without vascular disease, however, suggests that activated platelets may also basically contribute to the prethrombotic state in diabetes mellitus.

The prevalence of patients with concomitant heart failure (HF) and diabetes mellitus (DM) continues to increase with the general aging of the population. In patients with chronic HF, prevalence of DM is 24% compared with 40% in those hospitalized with worsening HF. Patients with concomitant HF and DM have diverse pathophysiologic, metabolic, and neurohormonal abnormalities that potentially contribute to worse outcomes than those without comorbid DM. In addition, although stable HF outpatients with DM show responses that are similar to those of patients without DM undergoing evidence-based therapies, it is unclear whether hospitalized HF patients with DM will respond similarly to novel investigational therapies. These data support the need to re-evaluate the epidemiology, pathophysiology, and therapy of HF patients with concomitant DM. This paper discusses the role of DM in HF patients and underscores the potential need for the development of targeted therapies.

This randomized clinical trial assesses the effect of application of cold atmospheric plasma in addition to standard care treatment compared with placebo on wound healing in terms of more rapid and clinical meaningful wound surface regression.

BACKGROUND We wished to investigate whether platelet activation is related to the clinical outcome during the 24 hours immediately after elective percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS In 102 patients with high-grade coronary stenosis admitted for elective PTCA, preprocedural platelet activation was characterized by flow cytometric measurement of the proteins CD62, CD63, and thrombospondin expressed on the platelet surface membrane. The prevalence of acute ischemic events during the 24 hours immediately after the procedure was then related to the pre-PTCA platelet activation status. Fifty-six patients were classified as "nonactivated," whereas 46 patients showed an increased percentage of activated platelets. Two patients developed acute occlusion (1.96%) and four patients high-grade restenosis (3.92%), as confirmed by second-look coronary angiography. All events occurred in patients classified as "activated" (six of 46, or 13%). None of these patients received beta-blocker medication, which was associated with lower expression of platelet membrane activation markers. In the nonactivated patient group, no clinical events were found (0 of 56, or 0%). This difference in prevalence is significant (p = 0.007). CONCLUSIONS We conclude that analysis of platelet membrane activation markers may help to predict an increased risk of acute ischemic events after angioplasty.