MULTICENTER INTERVENTION TRIAL TO PREVENT INSULIN-DEPENDENT DIABETES MELLITUS

1型糖尿病（1型DM）是由于免疫介导的胰岛胰岛素分泌B细胞破坏而在遗传易感个体中产生的。 糖尿病临床症状的出现代表了b细胞功能慢性进行性下降的终点，并且只有当大多数b细胞已经丢失时才会出现。 由于1型糖尿病的发展是隐性的，通常是在致病性免疫介导的破坏性过程诱导后数年，因此可以使用免疫学标记物和胰岛素分泌试验进行预测。1型糖尿病预防试验（DPT-1）旨在测试在疾病前驱期的干预是否可以延迟其临床发作。通过检测针对胰腺b细胞自身抗原的自身抗体，可以识别即将发生的临床1型糖尿病。 由于1型糖尿病先证者的一级亲属患1型糖尿病的风险是一般人群的10倍以上，因此DPT-1将重点关注这些亲属。 他们的初始血液（血清）筛查将是通过正常人胰腺切片中细胞质胰岛细胞抗原的间接免疫荧光检测胰岛细胞自身抗体（伊卡）。 那些发现患有伊卡的个体将根据其进展到临床疾病的时间点，被分为四种不同的1型糖尿病风险类别之一。 非糖尿病亲属中的1型糖尿病风险评估基于许多因素，包括：遗传易感性、年龄、伊卡的存在（特别是如果与胰岛素自身抗体（IAA）一起发现）以及静脉内葡萄糖耐量试验（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，“高风险”亲属将是基于伊卡阳性和IVGTT的低FPIR，预测在未来五年内至少有50%的可能性发展为1型DM的亲属。 中危亲属为伊卡阳性，但IVGTT FPIR正常者。 这一群体又可进一步分为因IAA阳性而具有“中等风险”的群体和IAA阴性而具有“中等风险”的群体。 “低风险”亲属缺乏伊卡。

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.