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

心脏病和中风仍然是英国男性和女性死亡和残疾的主要原因之一。糖尿病极大地增加了心脏病和中风的风险。然而，有令人信服的证据表明，糖尿病增加女性心脏病和中风的风险比男性高得多。这些性别差异背后的原因在很大程度上是未知的。这项研究旨在找出为什么糖尿病对女性心脏病和中风风险的影响似乎比男性更大。糖尿病的诊断是基于血液中任意的糖值。血糖水平略低于这一门槛的人患心脏病和中风的风险也更高。因此，在这项研究的第一部分，我将更好地描述不同水平的血糖如何增加心脏病、中风和其他糖尿病并发症(如慢性肾脏疾病和失明)的风险。我还将评估这一点在男性和女性之间是否存在差异。在第二部分中，我将使用遗传学原理来评估第一部分中针对性别的发现是否可能是因果关系。第三部分将探讨哪些生物因素可能导致女性罹患糖尿病相关的心脏病和中风的风险过高。此前的研究表明，男性和女性在体型、体重和肥胖方面的差异可能起到重要作用。女性特有的因素，如更年期或怀孕，也可能与此有关。这将得到进一步的调查。除了生物学上的解释，可能是卫生服务提供的不一致解释了为什么糖尿病患者的男性和女性的健康结果不同。例如，可能是女性的确诊时间晚于男性，或者她们没有接受与男性相同的治疗。因此，第四部分将根据推荐的指南，了解男性和女性糖尿病患者在提供医疗服务方面是否存在潜在差异。这项研究将提供关于男女在与糖尿病和血管疾病相关的健康行为、医疗保健和健康结果方面潜在重要差异的最佳现有证据。这一证据将指导卫生保健专业人员和政策制定者确定干预措施的优先顺序，并优化旨在减少与糖尿病相关的巨大健康负担和费用的卫生保健系统。它将提供与NHS直接相关的政策、管理和实践建议。最终，这项研究应该有助于(1)确保女性不会不成比例地受到糖尿病血管后果的影响，(2)优化全国范围内的医疗服务提供，(3)避免许多人患糖尿病，以及(4)改善糖尿病患者的生活。

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.