Timely topics in medicine. Cardiovascular diseases最新文献

Optimal glycemic control is essential for the prevention of diabetes-related complications, and the intensive insulin regimens that best resemble physiological insulin secretion are most likely to attain it. However, there are many limitations that preclude the early use of insulin by patients with type 2 diabetes or wider implementation of the intensive regimens in type 1 diabetes. More acceptable alternative routes of insulin administration and effective, noninvasive, patient-friendly delivery systems that alleviate the burden of insulin injections have been researched over the years. To date, only pulmonary inhalation of insulin has become a feasible alternative; it has proved to be as effective and well tolerated as the subcutaneously injected regular insulin and it has a pharmacodynamic profile well suited for mealtime insulin therapy. Several pulmonary insulin delivery systems are in different stages of development, and one (Exubera, Nektar Therapeutics/Pfizer Inc.-Sanofi-Aventis Group) has already become clinically available in the United States and Europe for patients with diabetes. Other noninjectable methods of insulin administration are reviewed.

There is significant evidence that low-dose aspirin is effective in preventing the first myocardial infarction in men and ischemic stroke in women. There is also an increased risk for major gastrointestinal tract hemorrhage and a suggestive, but nonsignificant, increase in the risk for hemorrhagic stroke. If there is a history of ulcer disease or upper-gastrointestinal tract bleeding, Helicobacter pylori should be eradicated (if present) and a proton pump inhibitor used with aspirin therapy. In conclusion, the benefits of low-dose aspirin (75-162 mg/day) in the prevention of myocardial infarction in men and thrombotic stroke in women generally outweigh the risks of serious bleeding in adults with a coronary heart disease risk >1% per year or >1% in 10 years.

The existence of links between Alzheimer's disease and diabetes is an important topic currently under active debate. Establishing such links if they exist and defining their common pathogenesis and pathophysiological mechanisms may lead to new concepts and research directions for the pharmacological treatment of Alzheimer's disease and diabetes. Alzheimer's disease is associated with peripheral and central insulin abnormalities. Cognitive capacities are often impaired in patients with diabetes. There are many mechanisms by which insulin-signaling abnormalities may affect clinical and pathological outcome of Alzheimer's disease. Insulin resistance and dysregulation of the degradation of neurotoxic amyloid and insulin appear at the core of the links between Alzheimer's disease and diabetes. Functions and expression of insulysin, an enzyme involved in the degradation of neurotoxic amyloid peptides and insulin, are usually impaired or reduced in Alzheimer's disease and diabetes. The increased occurrence of insulin resistance in Alzheimer's disease suggests that improving insulin effectiveness and insulysin activity may have therapeutic value in Alzheimer's disease patients and therefore is worth intensive investigation.

Diabetes UK held its Annual Professional Conference on March 29-31, 2006, in Birmingham, United Kingdom. This conference aimed to deliver the latest global developments in diabetes care using basic and clinical science as its cornerstone, and to inspire and support innovation in current practice. This report will examine the advances in different aspects of cardiovascular disease in diabetes mellitus.

The interaction of adenosine-5'-diphosphate (ADP) with its platelet receptors (P2Y1 and P2Y12) plays a very important role in thrombogenesis. The thienopyridine ticlopidine was the first specific antagonist of the platelet P2Y12 ADP receptor to be tested in randomized clinical trials for the prevention of arterial thrombotic events. Although ticlopidine reduces the incidence of vascular events in patients at risk, it also unfortunately has some significant drawbacks: a relatively high incidence of toxic effects, which may be fatal in some cases; delayed onset of action; and a high interindividual variability in response. A second thienopyridine, clopidogrel, has superseded ticlopidine, because it is also an efficacious antithrombotic drug and is less toxic than ticlopidine. However, clopidogrel is not completely free from faults: severe toxic effects, albeit occurring much less frequently than with ticlopidine, may still complicate its administration to patients; the onset of pharmacologic action can be accelerated by the use of large loading doses, but may still not be optimal; the high interpatient variability in response remains an important issue. These concerns justify the continued search for agents that can further improve the clinical outcome of patients with atherosclerosis through greater efficacy and/or safety. A new thienopyridyl compound, prasugrel, which is characterized by higher potency and faster onset of action compared with clopidogrel, is currently under clinical evaluation. Two direct and reversible P2Y12 antagonists, cangrelor and AZD6140, feature very rapid onset and reversal of platelet inhibition, which make them attractive alternatives to thienopyridines, especially when rapid inhibition of platelet aggregation or its quick reversal are required. Along with new the P2Y12 antagonists, inhibitors of the other platelet receptor for ADP, the antagonists P2Y1, are under development and may prove to be effective antithrombotic agents.