MULTICENTER INTERVENTION TRIAL TO PREVENT INSULIN-DEPENDENT DIABETES MELLITUS

预防胰岛素依赖型糖尿病的多中心干预试验

• 批准号: 6305132
• 负责人: DARRELL M WILSON
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6305132
• 关键词: autoantibody; clinical research; clinical trials; diabetes mellitus genetics; disease /disorder prevention /control; disease /disorder proneness /risk; family genetics; glucose tolerance test; human subject; insulin; insulin dependent diabetes mellitus; pancreatic islet function

Type 1 Diabetes Mellitus (Type 1 DM) arises in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin secreting b-cells. The onset of clinical symptoms of diabetes represents the end point of a chronic progressive decline in b-cell function, and it appears only when the majority of b-cells have been lost. Since Type 1 DM develops insidiously, often years after the induction of the pathogenic immune-mediated destructive process, it can be predicted using immunological markers and tests of insulin secretion. The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) been designed to test whether intervention during the prodromal period of the disease can delay its clinical onset. It is possible to identify impending clinical Type 1 DM through the detection of autoantibodies directed against self-antigens of the pancreatic b-cells. Since first degree relatives of probands with Type 1 DM have more than ten-fold the risk of Type 1 DM in the general population, the DPT-1 will focus on such relatives. Their initial blood (serum) screening will be for islet cell autoantibodies (ICA) detectable by the indirect immunofluorescence of cytoplasmic islet cell antigens in sections of normal human pancreas. Those individuals found to have ICA will then be staged into one of four different categories of risk of Type 1 DM, dependent upon their point of progression to the clinical disease. Type 1 DM risk assessment in non-diabetic relatives is based on a number of factors, including: genetic susceptibility, age, the presence of ICA especially if found together with insulin autoantibodies (IAA), and the degree of loss of first phase (1 + 3 minute) plasma insulin response (FPIR) during an intravenous glucose tolerance test (IVGTT). In the DPT-1, "High Risk" relatives will be those that have been predicted to have at least a 50% probability of developing Type 1 DM within the next five years on the basis of positive ICA and low FPIR to IVGTT. Moderate risk relatives are those with positive ICA, but normal FPIR to IVGTT. This group is further divisible into those with an "Intermediate Risk" on account of positive IAA and those with only a "Modest Risk" who are IAA negative. The "Low Risk" relatives lack ICA.

1型糖尿病(1型DM)是由于免疫介导的胰岛胰岛素分泌b细胞的破坏而在遗传易感个体中发生的。糖尿病临床症状的出现代表着b细胞功能慢性进行性下降的终点，只有当大多数b细胞丧失时才会出现。由于1型糖尿病是潜伏发展的，通常在致病免疫介导的破坏性过程诱导数年后，可以使用免疫标记物和胰岛素分泌测试来预测它。1型糖尿病预防试验(DPT-1)旨在测试在疾病的前驱时期进行干预是否可以推迟其临床发病。通过检测针对胰腺b细胞自身抗原的自身抗体，有可能识别即将到来的临床1型糖尿病。由于1型糖尿病先证者的一级亲属在普通人群中患1型糖尿病的风险是前者的十倍以上，DPT-1将重点关注这些亲属。他们最初的血液(血清)筛查将是胰岛细胞自身抗体(ICA)的筛选，该抗体可通过正常人胰腺切片中胰岛细胞抗原的间接免疫荧光来检测。然后，那些被发现患有ICA的人将被分成四种不同的1型糖尿病风险类别之一，这取决于他们发展为临床疾病的时间点。非糖尿病亲属的1型糖尿病风险评估基于许多因素，包括：遗传易感性、年龄、ICA的存在，特别是当发现与胰岛素自身抗体(IAA)一起出现时，以及静脉葡萄糖耐量试验(IVGTT)期间第一时相(1+3分钟)血浆胰岛素反应(FPIR)的丧失程度。在DPT-1中，“高危”亲属将是那些在ICA阳性和IVGTT的低FPIR的基础上，预测在未来五年内至少有50%的可能性发展为1型糖尿病的亲属。中度风险亲属是ICA阳性，但FPIR至IVGTT正常的人。这一组还可进一步分为IAA阳性的“中等风险”者和IAA阴性的“中等风险”者。“低风险”亲属缺乏ICA。