Diabetes, incretin hormones and cardioprotection

In 2012 an estimated 371 million people had diabetes and of those about a half were undiagnosed. That number is set to expand to 552 million by 2030. Type 2 diabetes mellitus (T2DM) constitutes 85–95% of all diabetes in high income nations and may account for an even greater proportion in their low and middle income counterparts (figure 1). As a global pandemic, diabetes claimed the lives of 4.8 million people in 2012, half of whom were below the age of 60 years.w1 The predominant cause of morbidity and mortality in diabetes is cardiovascular disease, with at least a twofold excess risk of developing a multitude of vascular pathologies including ischaemic heart disease, different stroke subtypes, peripheral arterial disease, and heart failure.w2 w3 Indeed, as many as 80% of T2DM patients will develop and possibly die from macrovascular complications.w3 Such stark findings have led many to regard diabetes as a coronary heart disease risk equivalent, to a level at which non-diabetic individuals with a previous history of acute coronary syndrome (ACS) would reside. Figure 1 The International Diabetes Federation Diabetes Update 2012. Diabetes has become a truly global pandemic. Urbanisation, changes in lifestyle, and improvements in healthcare systems combine to increase an individual's risk of acquiring the condition. Reproduced with permission from the International Diabetes Foundation. For many years this enhanced cardiovascular risk was thought to be a solely atherosclerosis driven process characterised by endothelial cell dysfunction, oxidative stress, vessel remodelling, impaired vasodilatation, and subendothelial plaque formation. Latterly the concept of the vulnerable patient emerged to highlight the complex interplay between a constellation of deleterious processes spearheaded not only by the vulnerable vessel/plaque but also by vulnerable blood constituents and a vulnerable myocardium; together these processes shift an individual towards a greater susceptibility to developing cardiovascular complications.w4 w5 It …