Sex differences in the vascular consequences of diabetes: big data analyses to inform prevention and treatment

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Heart disease and stroke remain one of the leading causes of death and disability in both men and women in the UK. Diabetes substantially increases the risk of heart disease and stroke. However, there is compelling evidence that diabetes increases the risk of heart disease and stroke much more in women than in men. The reasons which underlie these sex differences are largely unknown. This research aims to find out why diabetes appears to have a stronger effect on the risk of heart disease and stroke in women than in men. The diagnosis of diabetes is based on an arbitrary value of sugar in the blood. People with levels of blood sugar just below that threshold are also at higher risk for heart disease and stroke. In the first part of this research, I will therefore better characterise how different levels of blood sugar increase the risks of heart disease, stroke, and other complications of diabetes such as chronic kidney disease and blindness. I will also assess whether this differs between men and women. In part two, I will use genetic principles to assess whether the sex-specific findings from part one are likely to be causal. Part three will look at which biological factors may underpin women's excess risk of heart disease and stroke associated with diabetes. Previous studies have suggested that differences between men and women in body shape, body weight, and obesity may play an important role. Factors unique to women, such as the menopause or pregnancy may also be involved. This will be further investigated. Apart from biological explanations, it may be that inconsistencies in health service delivery explain why the health outcomes in men and women with diabetes are different. For example, it may be that women are diagnosed later than men or that they do not receive the same treatments as men. Thus, part four will see whether there are potential differences between men and women with diabetes in health service delivery according to the recommended guidelines. This research will deliver the best available evidence on potentially important differences between women and men in the health behaviours, health care, and health outcomes associated with diabetes and vascular diseases. This evidence will guide health care professionals and policymakers in prioritising interventions and in optimising health care systems aimed at reducing the large health burden and costs associated with diabetes. It will provide policy, management and practice recommendations that will be of direct relevance to the NHS. Ultimately, this research should help to (1) ensure that women are not disproportionally affected by the vascular consequences of diabetes, (2) optimise health service delivery nationwide, (3) avert the onset of diabetes in many individuals, and (4) improve the lives of people living with diabetes.