Fig. 1. Top 10 global causes of death, 2016. Blue = Non-communicable diseases; Green = Communicable, maternal, neonatal and nutritional conditions; Yellow = Injuries. Adapted from [2].
This chapter provides an overview of the relationship between diabetes and cardiovascular risk and explores methods of determining cardiovascular risk in individuals, including risk scores and biomarkers.
Epidemiology of Diabetes Mellitus
Diabetes mellitus is a major cause of morbidity and premature mortality worldwide with an estimated 451 million adults affected in 2017, almost half of whom are currently undiagnosed [5]. The number of people with diabetes is forecast to rise to 693 million by 2045. Determining the type of diabetes in large epidemiological studies is difficult, but the vast majority of cases, about 90%, are thought to have type 2 diabetes [6]. Currently, care of people with diabetes accounts for approximately USD 850 billion of global healthcare expenditure [5]. Since 1980, the number of people living with diabetes worldwide has almost quadrupled [7]. This is in part due to population growth and ageing, but also represents a true increase in prevalence. The epidemic of type 2 diabetes is closely linked to the rising prevalence of obesity and is contributed by numerous factors including globalisation and urbanisation, with increasingly sedentary lifestyles and greater caloric intake [8].
The diabetes epidemic has been characterised by substantial variation between geographic locations, ethnicities and cultural groups. Low- and middle-income countries have seen the greatest increases in diabetes prevalence over recent decades and this disparity is predicted to continue (Fig. 2) [5, 7]. This has been attributed to differences in both genetic and environmental factors, with potential interactions between them. There is evidence that the intrauterine environment and foetal nutrition can impact gene expression via epigenetic changes [9]. Thus, maternal health can potentially impact the chronic disease risk of subsequent generations. Such factors are theorised to have contributed to the dramatic increases in prevalence in resource-poor settings.
Fig. 2. Estimated number of people (aged 20–79 years) with diabetes worldwide and per region in 2017 and 2045. With permission from: IDF Diabetes Atlas Eighth Edition 2017. Brussels, International Diabetes Federation, 2017.
Diabetes and Vascular Disease Mechanisms
Diabetes mellitus is a metabolic disorder characterised by chronic hyperglycaemia as well as disruption to fat, carbohydrate and protein metabolism. Hyperinsulinaemia, insulin resistance and pancreatic β-cell failure are typical of type 2 diabetes. Type 1 diabetes is an immune-mediated condition, usually with detectable autoantibodies, which results in the destruction of β-cells and insulin deficiency. Other rarer forms of diabetes include, among others, monogenic diabetes, drug-induced diabetes and diseases of the exocrine pancreas.
Diabetes complications are traditionally classified into microvascular complications such as neuropathy, retinopathy and nephropathy; and macrovascular complications such as ischaemic heart disease, stroke and peripheral arterial disease. Ischaemic heart disease remains the most common cause of mortality in patients with diabetes, typically presenting at an earlier age, with greater severity and more diffuse atherosclerotic disease than in patients without diabetes [10]. More recently, heart failure has emerged as an important manifestation of heart disease in people with diabetes. While it may be a consequence of coronary artery disease and myocardial infarction, there is strong evidence of a direct metabolic effect on cardiac function, leading to fibrosis and stiffness of the ventricles and reduced filling volumes [11]. Indeed, recent data show that, in diabetes, heart failure frequently presents before there have been any clinical episodes of coronary artery disease [12].
Mechanisms for the development of atherosclerotic cardiovascular disease associated with hyperglycaemia include endothelial dysfunction, hypercoagulability, advanced glycation end product formation, increased platelet reactivity, increased oxidative stress and increased inflammation [10, 13]. Due to shared risk factors, people with diabetes often have concomitant disorders contributing to their cardiovascular risk, such as hypertension, dyslipidaemia, obesity and obstructive sleep apnoea. Furthermore, insulin-resistance, even prior to the onset of hyperglycaemia, may affect lipid metabolism directly, leading to elevated triglycerides, low high-density lipoprotein and small dense low-density lipoproteins (LDL) [10]. This pattern of dyslipidaemia is known to be atherogenic.
Trends in Cardiovascular Risk and Mortality
Over the last 2 decades, there has been a significant decline in rates of cardiovascular mortality globally. However, absolute numbers of premature cardiovascular deaths continue to rise in low- and middle-income countries [14]. Patterns in cardiovascular mortality vary greatly between geographic regions. While globally ischaemic heart disease accounts for the majority of cardiovascular deaths, there are some regions, particularly East and Southeast Asia and Sub-Saharan Africa, where stroke is the dominant cause. This is in part due to higher rates of haemorrhagic stroke. It is unclear how much of the difference in stroke mortality relates to differences in incidence versus differences in case fatality [14].
Falling mortality trends have also been observed among people with diabetes in developed countries. For example, in Australia, both all-cause and cardiovascular mortality risk have declined significantly in both type 1 and 2 diabetes [15]. Figure 3 depicts trends over time in standardised mortality ratios for all-cause mortality in people with type 2 diabetes compared to the non-diabetic population. Despite significant improvements, an excess risk of mortality associated with diabetes remains.
Fig. 3. Standardised mortality ratios for all-cause mortality among men (a) and women (b) with type 2 diabetes between 1997 and 2010 in Australia. Source: Harding et al. [15].
In addition to improvements in mortality rates, data from the United States
