Longitudinal and genetic evaluation of type 2 diabetes and major depression

抑郁症和2型糖尿病是日益严重的健康问题，对个人和社会都有很高的成本。大多数研究集中在抑郁症或2型糖尿病上。然而，患有抑郁症和2型糖尿病的人比我们预期的要多，因此需要更多的研究来了解这两种疾病之间的复杂关系。目前有许多问题没有得到解答。例如，患有抑郁症和2型糖尿病是否会增加其他不良健康后果的风险（例如心脏问题，腿部溃疡等）。比单纯的抑郁症或2型糖尿病更严重吗我们的研究旨在使用来自大型研究的信息，包括遗传数据和初级卫生保健记录，以测试如何：a）抑郁症和2型糖尿病彼此相关，B）危险因素c）患有2型糖尿病和抑郁症两者影响个体的健康，d）抑郁症随时间改变2型糖尿病患者的葡萄糖水平，以及e）诊断的顺序和年龄改变结果。为了验证我们的假设，我们将使用两种不同但互补的方法。首先，我们将使用遗传学来推断因果关系，即评估我们看到的关系是否是真实的，而不是由数据中的“噪音”引起的。这是可能的，因为我们的遗传密码在出生前就已经固定了，不会因为我们的饮食或生活方式因素而改变，比如吸烟，否则可能会导致偏见。因此，基因是检验两个因素之间真正因果关系的有用工具。例如，如果抑郁症与2型糖尿病有直接联系，那么增加抑郁症风险的基因也会对2型糖尿病产生影响。从公共卫生的角度来看，了解因果关系是很重要的，以确保适当的监测和治疗计划到位，并为患者。其次，我们将使用来自全科医生（GP）记录的数据，这些数据来自20多万名2型糖尿病和抑郁症患者。这将使我们能够回答几个重要的问题。首先，我们将测试抑郁症如何随着时间的推移改变血糖水平。所有2型糖尿病患者定期（约每6个月）在GP中进行血糖监测。我们将测试抑郁症和2型糖尿病是否以及如何随着时间的推移改变血糖水平的变化，并确定诊断的相对时间（即2型糖尿病之前的抑郁症或反之亦然）是否重要。其次，我们将关注抑郁症患者，并测试2型糖尿病是否会改变抑郁症的进展。例如，患有这两种疾病的人是否会有更多的抑郁发作，或者他们更有可能患上更严重的抑郁症？我们的研究结果对抑郁症和2型糖尿病患者至关重要。我们将在我们对这种关系的理解方面提供一个步骤，并将与临床医生和患者合作，以确保我们的研究结果转化为适当的公共卫生信息，这有可能改善2型糖尿病和抑郁症患者的治疗途径和干预措施。

Depression and type 2 diabetes are growing health problems, with high costs to both individuals and society. Most research focuses on either depression or on type 2 diabetes. However, more people have both depression and type 2 diabetes than we would expect and therefore more research is needed to understand the complex relationship between these two conditions. At the moment there are many unanswered questions. For example, does having both depression and type 2 diabetes increase your risk of other adverse health outcomes (e.g. heart problems, leg ulcers etc.) further than having depression or type 2 diabetes alone?Our research aims to use information from large studies with genetic data and primary health care records to test how: a) depression and type 2 diabetes are related to one another, b) risk factors (such as education and obesity) influence the depression and type 2 diabetes relationship, c) having both type 2 diabetes and depression impacts an individual's health, d) depression alters glucose levels for type 2 diabetics over time and e) the order and age of diagnoses alter outcomes. To test our hypotheses, we will use two different but complementary approaches. Firstly, we will use genetics to allow us to infer causality, i.e. assess whether the relationships we see are real and not caused by 'noise' in the data. This is possible because our genetic code is fixed before birth and does not change as a result of our diet or lifestyle factors, such as smoking, which might otherwise lead to bias. Genes are therefore useful tools for testing the true causal link between two factors. For example, if there is a direct link from depression to type 2 diabetes, genes that increase the risk of depression will also have an effect on type 2 diabetes. Understanding the causal relationship is important from both a public health perspective, to ensure appropriate monitoring and treatment plans are in place and for patients. Secondly, we will use data from general practitioner (GP) records in over 200,000 patients with both type 2 diabetes and depression. This will allow us to answer several important questions. Firstly, we will test how depression alters blood glucose levels over time. All patients with type 2 diabetes are seen at the GP regularly (~ every 6 months) to have their glucose monitored. We will test if and how having depression as well as type 2 diabetes alters the changes in glucose levels over time and determine whether the relative timing of diagnosis (i.e. depression before type 2 diabetes or vice versa) is important. Secondly, we will focus on individuals with depression and test if having type 2 diabetes alters the progression of depression. For example, do individuals with both conditions have more depression episodes or are they more likely to develop more severe depression?Our findings will be of crucial importance to individuals with both depression and type 2 diabetes. We will provide a step change in our understanding of this relationship and will work with clinicians and patients to ensure our findings are translated into appropriate public health messaging, which have the potential to improve treatment pathways and interventions for individuals with both type 2 diabetes and depression.