Insulin Resistance: The Cardiovascular Aspect

Introduction

This Special Issue contains a series of reviews and original articles covering broadly, although not exhaustively, the mechanisms that link insulin resistance (IR) to cardiovascular diseases.

The association between diabetes and cardiovascular disease (CVD) has been recognized for decades [1] [2] [3] [4]. Furthermore, once coronary artery disease is established, outcomes are poor in patients with diabetes undergoing percutaneous revascularization [5] [6] making coronary by-pass a preferred option for these patients [7].

Although the cardiovascular risk in diabetes has been well established for a long time, it was disappointing to find that earlier intervention trials aiming at correction of hyperglycemia did not bring any substantial improvements in terms of spared cardiovascular events as expected [8] [9]. While intensive poly-pharmacological intervention has been shown to reduce the development of vascular complications [10] and mortality [11], it is not possible to attribute these benefits to correction of hyperglycemia per se. Accordingly, the results of the ACCORD study [12], aiming at establishing the cardiovascular profit of full normalization of glycemia control, was awaited with interest. Surprisingly, the intensive blood glucose control sub-study in the ACCORD-trial was stopped prematurely in February 2008, due to safety concerns (www.diabetes.org/for-media/pr-ada-statement-related-to-accord-trail-announcement-020608.jsp). The exact reasons for the increased mortality in the intensive treatment arm are not yet identified. Nevertheless, it has become clear that IR rather than the overt diabetes influences the cardiovascular outcome [13] [14] [15] [16] [17]. Conversely, the presence of hyperglycemia at the moment of a cardiac event confers a mortality risk that exceeds by far that of having overt diabetes, even though this does not imply that the patient will develop diabetes [18]. Altogether, it seems evident that hyperglycemia exerts different roles in different situations, ranging from being just a marker of IR, or a marker of lack of insulin, or both [19] to being a major trigger of cardiovascular injury [20] [21].

This issue deals with some key mechanisms leading to CVD taking IR as reference, rather than diabetes or the metabolic syndrome, although still taking into consideration that these conditions share overlapping features [19] [22] [23] [24] [25].

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