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Handbook of Diabetes, 4th Ed., Excerpt #19: Macrovascular Disease in Diabetes

Rudy Bilous, MD, FRCP
Richard Donnelly, MD, PHD, FRCP, FRACP


For any given age, level of cholesterol or BP, the risk of atherosclerotic cardiovascular disease (CVD) is 3 to 5-fold higher among patients with diabetes compared with subjects without diabetes. Macrovascular complications include fatal and non-fatal coronary heart disease (CHD) events, stroke and peripheral arterial disease (PAD). CVD accounts for most (more than 75%) of the premature mortality and shortened life expectancy among patients with diabetes. It affects both genders equally, and in particular the protective effect of premenopausal status is lost in women with diabetes. Within the diabetic population, hypertension and especially proteinuria (nephropathy) have a multiplying effect on CVD risk and there is a strong inverse relationship between urinary albumin excretion rate and survival (Figures 20.1 and 20.2). Some ethnic groups are particularly susceptible to CVD complicating diabetes (e.g. South Asians in the UK and blacks in the USA), while others are relatively protected (e.g. Native Americans, such as the Pima Indians, and Hispanic whites in the USA).



Histologically, atherosclerotic disease in patients with diabetes is similar to that in people without diabetes, but plaques tend to be more diffuse in nature and involve more distal, smaller arteries, which often makes revascularization (angioplasty/stenting or bypass) less feasible. In patients with diabetes, atherosclerotic disease occurs at a younger age and progresses more rapidly, and plaque rupture leading to superimposed thrombus and major vessel occlusion is more common (Figure 20.3). Outcomes from acute myocardial infarction (AMI) and stroke are all consistently worse in patients with diabetes compared with people without diabetes, e.g. rates of coronary reperfusion and reocclusion, left ventricular function and sudden death. There is also an inflammatory component to atherosclerotic disease progression and plaque rupture, and several studies have shown a relationship between the risk of CVD events and circulating inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP).

Peripheral arterial disease in patients with diabetes typically involves multiple vessels with diffuse, distal narrowing, and there is a 40-fold increased risk of lower limb amputation. The smaller arteries and arterioles are damaged further by microvascular disease affecting the vasa vasorum (the tiny nutrient vessels which supply oxygen to the arterial wall itself), which makes the medial layer of arteries prone to calcification, known as ‘Mönckeberg’s medial calcific sclerosis’, which is often seen in the digital arteries of patients with diabetes and nephropathy and/or neuropathy (Figure 20.4).