Platelet Resistance to the Anti-Aggregating Agents in the Insulin Resistant States

Authors: Anfossi, Giovanni; Russo, Isabella; Trovati, Mariella

Source: Current Diabetes Reviews, Volume 2, Number 4, November 2006 , pp. 409-430(22)

Publisher: Bentham Science Publishers

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Abstract:

Insulin resistance is a relevant risk factor for the major cardiovascular events, caused by severe atherosclerotic involvement of coronary, cerebral and lower limb blood vessels.

One of the alterations accounting for this increased cardiovascular risk is the impairment of platelet function, explained, at least in part, by the reduced sensitivity to the physiological and pharmacological anti-aggregating agents.

In the first part of this review, we will focus our attention on the physiological mechanisms involved in the attenuation of platelet response and on their impairment in insulin resistance, considering in particular: i) the reduced sensitivity to insulin and other substances acting via intracellular cyclic nucleotides; ii) the altered intracellular ionic milieu with elevated cytosolic Ca2+, iii) the increase of oxidative stress, which elicits isoprostane production from arachidonic acid.

Therapeutic guidelines recommend a multifactorial prevention including antiplatelet drugs, even though the protective effect of antiplatelet therapy in both obese and type 2 diabetic patients has not been completely clarified so far. Furthermore, some reports show a decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic acid in obesity and type 2 diabetes mellitus. These defects explain why antiplatelet therapy for both chronic atherosclerotic vascular disease and acute coronary syndromes should be specifically tailored in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus.

Thus, in the second part of this review we performed a critical overview of the clinical trials on anti-aggregating agents carried out in subjects with metabolic syndrome and type 2 diabetes mellitus.

Keywords: Aspirin; Cardiovascular disease; Insulin; nsulin resistance; Nitric oxide; Obesity; Platelets; Thienopyridines; Type 2 diabetes mellitus

Document Type: Research article

Publication date: 2006-11-01

More about this publication?

Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy.

The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.

Platelet Resistance to the Anti-Aggregating Agents in the Insulin Resistant States

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