Challenging the dogma of homogeneity in gestational diabetes

挑战妊娠糖尿病同质性的教条

• 批准号: MR/W003740/1
• 负责人: Sara White
• 金额: $ 112.94万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW003740%2F1
• 关键词: Challenging; dogma; homogeneity; gestational; diabetes

The number of women who develop diabetes in pregnancy (gestational diabetes) is increasing. Women of South Asian ethnicity are particularly affected. This common disorder which is associated with high blood glucose increases the risk of several pregnancy complications, most of which relate to the baby growing too large. These risks include difficulties during labour and stillbirth. Also, there is increased chance of the mother developing lifelong type 2 diabetes.At present, all women who develop gestational diabetes receive the same treatment approach. This is because doctors view gestational diabetes as one condition. Research in non-pregnant people with type 2 diabetes is beginning to show that there may be many different types of diabetes. Similarly, evidence is emerging which suggests that doctors should think of gestational diabetes as a group of different disorders, all leading to high blood glucose. This study aims to unpick the different types of gestational diabetes and we shall see if these are the same in South Asian and White European women. If successful we shall then be able to treat each woman according to their type of diabetes, and work towards preventing type 2 diabetes after pregnancy.This work will begin by defining more accurately two proposed pathways to GDM:-1. GDM arising from problems of glucose uptake in the liver, fat and skeletal muscle. In one subtype of GDM, it is proposed that the normal transfer of glucose into tissues is reduced because the tissues don't respond to insulin, leading to glucose not being taken up from the blood, resulting in raised blood levels.2. GDM arising from inefficient secretion of insulin from the beta-cells of the pancreas. In normal pregnancy, all women become a little insulin resistant, but cells in the pancreas (beta-cells) respond by producing more insulin. In this, second type of GDM it is proposed that the pancreatic insulin response is insufficient, and glucose rises in the blood.We will recruit 750 pregnant women (400 White European, 350 South Asian, calculated on the basis of the likely number of women who will develop GDM) at the time of their first scan (11-15 weeks of pregnancy). As we are interested in glucose levels and how well the body is producing insulin (the hormone that controls glucose) throughout pregnancy, women will undertake two sugar stress tests (the oral glucose tolerance test; OGTT); one in early pregnancy (12-16 weeks), and one at the normal time for diagnosis of gestational diabetes (24-28 weeks), and blood samples will be stored. We will also ask some simple questions and measure glucose using a stick-on glucose sensor (CGM) in addition to following the growth of the baby during pregnancy. We will then undertake a detailed analysis of the blood samples, measuring a range of molecules which we know are associated with diabetes and blood glucose management. By combining this data together we hope to define with accuracy the different ways each of the subtypes develop gestational diabetes, so we can offer each woman the most appropriate treatment. We will look for differences and similarities between women of White European descent and women of South Asian descent. Having achieved a better understanding of the GDM subtypes we will be well positioned to develop specific tests for each type of GDM to help doctors decide on which treatment would work best for each individual. We shall also find out if the same or slightly different tests early in pregnancy can pick up women who will later develop GDM subtypes, so that doctors can intervene to prevent GDM.

妊娠期患糖尿病（妊娠期糖尿病）的妇女人数正在增加。南亚族裔的妇女尤其受影响。这种与高血糖相关的常见疾病增加了几种妊娠并发症的风险，其中大多数与婴儿长得过大有关。这些风险包括分娩困难和死产。此外，母亲患终身2型糖尿病的几率也会增加。目前，所有患妊娠期糖尿病的妇女都接受同样的治疗方法。这是因为医生将妊娠期糖尿病视为一种疾病。对未怀孕的2型糖尿病患者的研究开始表明，可能有许多不同类型的糖尿病。同样，越来越多的证据表明，医生应该将妊娠糖尿病视为一组不同的疾病，所有这些疾病都会导致高血糖。这项研究旨在分析不同类型的妊娠糖尿病，我们将看看这些在南亚和欧洲白人妇女中是否相同。如果成功，我们将能够根据每个妇女的糖尿病类型来治疗，并努力预防怀孕后的2型糖尿病。这项工作将从更准确地定义GDM的两种途径开始：-1。由肝脏、脂肪和骨骼肌的葡萄糖摄取问题引起的GDM。在GDM的一种亚型中，有人提出，由于组织对胰岛素没有反应，葡萄糖向组织的正常转移减少，导致葡萄糖没有从血液中吸收，导致血液水平升高。由胰腺β细胞分泌胰岛素的效率低下引起的糖尿病。在正常怀孕期间，所有女性都会产生一点胰岛素抵抗，但胰腺细胞（β细胞）的反应是产生更多的胰岛素。在第二种类型的GDM中，提出胰腺胰岛素反应不足，血液中葡萄糖升高。我们将招募750名孕妇（400名白种欧洲人，350名南亚人，根据可能患GDM的妇女人数计算）在第一次扫描时（怀孕11-15周）。由于我们对整个怀孕期间的血糖水平和身体产生胰岛素（控制血糖的激素）的情况感兴趣，妇女将进行两次糖压力测试（口服葡萄糖耐量试验；OGTT）；妊娠早期（12-16周）一次，妊娠糖尿病诊断正常时间（24-28周）一次，并保存血样。我们还会问一些简单的问题，并使用黏贴式葡萄糖传感器（CGM）测量葡萄糖，除了在怀孕期间跟踪婴儿的生长情况。然后，我们将对血液样本进行详细分析，测量一系列我们知道与糖尿病和血糖管理有关的分子。通过将这些数据结合在一起，我们希望准确地定义每种亚型发展为妊娠糖尿病的不同方式，这样我们就可以为每位女性提供最合适的治疗。我们将寻找欧洲白人女性和南亚女性之间的异同。在对GDM亚型有了更好的了解后，我们将有能力为每种类型的GDM开发特定的测试，以帮助医生决定哪种治疗方法对每个人最有效。我们还将发现，在怀孕早期进行相同或略有不同的测试，是否能发现后来会发展为GDM亚型的女性，以便医生进行干预，预防GDM。