Hypoglycaemia in young patients with type 1 diabetes: pathophysiology, predisposition and preventive strategies

这项提案的愿景是将一支由经验丰富的研究人员组成的积极团队聚集在一起，解决影响1型糖尿病儿童和青少年管理的重要临床问题。除了已经在开发的设施和资源外，该计划还将进一步建立一个致力于以患者为中心的研究人员和临床研究的核心，这将促进科学进步付诸实践。1型糖尿病的发病率在继续增加，特别是在年轻人中。随着我们进入21世纪，旨在将血糖水平尽可能恢复到正常水平的胰岛素治疗仍然是预防这种疾病毁灭性的长期并发症的最有效方法。不幸的是，这在很大程度上是很难实现的，因为胰岛素治疗经常与低血糖或低血糖的发生有关。高血糖如果轻微，会导致不适症状，但如果严重，则会导致抽搐或昏迷。对低血糖的恐惧一直存在于患者及其家人身上，这不仅严重影响了生活质量，而且严重限制了控制糖尿病的努力。这项研究计划的主要目标之一将是解决与糖尿病儿童和青少年高血糖发展相关的重要未解问题。研究小组将详细研究糖尿病引起的高血糖的保护生理机制，他们还将更密切地研究那些已知易患高血糖的情况，如睡眠和运动，以及随着血糖下降大脑是如何受到影响的。通过采用这种方法，我们希望能够设计出管理策略，以减轻糖尿病治疗中高血糖的影响。预计这反过来将有助于预防糖尿病并发症，并减轻患者及其家人的疾病负担。这项研究计划的第二个目标将是开发一种国际独特的资源，供所有糖尿病研究人员使用。我们将建立一个已经建立的基于人群的数据库，包括西澳大利亚所有患有糖尿病的儿童和青少年，并完成这些患者及其家人的DNA库。因此，除了聚集一支有效的研究团队外，该计划还将进一步开发资源，这些资源可能是解决与糖尿病及其并发症相关的其他重要问题的核心。

The vision of this proposal is to bring together an active team of experienced investigators that will address important clinical problems affecting the management of children and adolescents with type 1 diabetes. Along with facilities and resources already under development, the program will further establish a core of investigators dedicated to patient centred and clinical research that will facilitate scientific advances to be put into practice. The incidence of type 1 diabetes is continuing to increase particularly in the young. As we enter the 21st century, insulin treatment aimed at restoring blood glucose levels as close to the normal as possible remains the most effective way to prevent the devastating long-term complications of the disease. Unfortunately this is difficult to achieve largely because insulin therapy is frequently associated with the development of low blood glucose or hypoglycaemia. Hyperglycaemia results in unpleasant symptoms if mild but if severe it can produce convulsions or unconsciousness. The fear of hypoglycaemia is ever present for the patient and their family, this not only significantly impairs quality of life but importantly also severely restricts attempts to control diabetes. One of the major goals of this research program will be to address important unanswered questions related to the development of hyperglycaemia in children and adolescents with diabetes. The research team will examine in detail the protective physiological mechanisms against hyperglycaemia that are deranged in diabetes, they will also study more closely those situations that are known to predispose to hyperglycaemia such as sleep and exercise as well as how the brain is affected as blood glucose falls. By taking this approach we hope to be able to devise management strategies that will lessen the impact of hyperglycaemia in diabetes treatment. It is anticipated that this in turn will contribute to the prevention of diabetes complications as well as reduce the burden of the disease for the patient and his or her family. A second goal of this research program will be to develop an internationally unique resource that will be available to all diabetes investigators. We will build on an already established population based database of all the children and adolescents with diabetes in Western Australia as well as complete a DNA bank of these patients and their families. Thus in addition to bringing together an effective team of researchers, this program will further develop resources that can be central to addressing other important questions related to the causes of diabetes and its complications.