Challenging the dogma of homogeneity in gestational diabetes

妊娠期糖尿病（妊娠期糖尿病）的妇女人数正在增加。南亚族裔妇女尤其受到影响。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，其中大多数与婴儿生长过大有关。这些风险包括分娩困难和死胎。此外，母亲患终身2型糖尿病的机会增加。目前，所有患妊娠糖尿病的妇女都接受相同的治疗方法。这是因为医生认为妊娠糖尿病是一种疾病。对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，有证据表明，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。本研究旨在分析不同类型的妊娠期糖尿病，我们将观察南亚和白色欧洲妇女的妊娠期糖尿病是否相同。如果成功的话，我们将能够根据每个妇女的糖尿病类型进行治疗，并致力于预防妊娠后2型糖尿病。这项工作将开始，更准确地定义两种建议的GDM途径：GDM是由肝脏、脂肪和骨骼肌的葡萄糖摄取问题引起的。在GDM的一种亚型中，有人提出，由于组织对胰岛素不起反应，葡萄糖正常转移到组织中减少，导致葡萄糖不能从血液中吸收，从而导致血液水平升高。GDM是由胰腺β细胞胰岛素分泌不足引起的。在正常妊娠中，所有女性都会产生一点胰岛素抵抗，但胰腺细胞（β细胞）会产生更多的胰岛素。我们将招募750名孕妇（400名白色欧洲人，350名南亚人，根据可能发生GDM的妇女人数计算）进行首次扫描（妊娠11-15周）。由于我们对葡萄糖水平以及整个怀孕期间身体产生胰岛素（控制葡萄糖的激素）的情况感兴趣，因此女性将进行两次糖负荷试验（口服葡萄糖耐量试验; OGTT）;一次在怀孕早期（12-16周），一次在正常时间诊断妊娠糖尿病（24-28周），并储存血液样本。我们还将询问一些简单的问题，并使用粘贴式葡萄糖传感器（CGM）测量葡萄糖，以及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，测量一系列我们已知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，我们希望准确地定义每种亚型发展妊娠糖尿病的不同方式，以便我们可以为每位女性提供最合适的治疗。我们将寻找白色欧洲血统的妇女和南亚血统的妇女之间的差异和相似之处。在对GDM亚型有了更好的了解之后，我们将能够很好地为每种类型的GDM开发特定的测试，以帮助医生决定哪种治疗方法最适合每个人。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可以检测出以后会发展为GDM亚型的妇女，以便医生可以干预以预防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.