Challenging the dogma of homogeneity in gestational diabetes

患妊娠期糖尿病(妊娠期糖尿病)的妇女人数正在增加。南亚裔妇女受到的影响尤其大。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太大有关。这些风险包括分娩困难和死产。此外，母亲患终生2型糖尿病的几率也增加了。目前，所有患有妊娠期糖尿病的妇女都接受相同的治疗方法。这是因为医生将妊娠期糖尿病视为一种疾病。对非怀孕的2型糖尿病患者的研究开始表明，可能存在许多不同类型的糖尿病。同样，正在出现的证据表明，医生应该将妊娠期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。这项研究旨在揭示不同类型的妊娠期糖尿病，我们将看看这些在南亚和欧洲白人女性中是否相同。如果成功，我们将能够根据每个妇女的糖尿病类型来治疗她们，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两条拟议的GDM途径开始：-1。妊娠期糖尿病是由肝脏、脂肪和骨骼肌的葡萄糖摄取问题引起的。在GDM的一个亚型中，有人认为葡萄糖向组织中的正常转移减少，因为组织对胰岛素没有反应，导致葡萄糖不能从血液中被吸收，从而导致血液水平升高。妊娠期糖尿病由胰腺的β细胞低效分泌胰岛素引起。在正常怀孕期间，所有女性都会对胰岛素产生少许抵抗，但胰腺中的细胞(β细胞)会产生更多的胰岛素。在第二种类型的妊娠期糖尿病中，建议胰腺胰岛素反应不足，血糖升高。我们将招募750名孕妇(400名欧洲白人，350名南亚孕妇，基于可能发展为妊娠期糖尿病的妇女的数量计算)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分泌胰岛素(控制血糖的激素)的情况很感兴趣，女性将接受两次糖负荷测试(口服葡萄糖耐量测试；OGTT)；一次是在怀孕早期(12-16周)，另一次是在正常时间诊断妊娠期糖尿病(24-28周)，血液样本将被储存。我们还将问一些简单的问题，并使用粘贴式血糖传感器(CGM)测量血糖，此外还会跟踪婴儿在怀孕期间的生长情况。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相关的分子。通过将这些数据结合在一起，我们希望准确地确定每种亚型患妊娠期糖尿病的不同方式，这样我们就可以为每一位妇女提供最合适的治疗。我们将寻找欧洲白人后裔女性和南亚裔女性之间的差异和相似之处。在对妊娠期糖尿病的亚型有了更好的了解后，我们将很好地为每种类型的妊娠期糖尿病开发具体的测试，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检测是否可以发现以后会发展为GDM亚型的妇女，以便医生能够干预以预防GDM。

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.