IMPROVING METABOLIC ASSESSMENTS IN TYPE 1 DIABETES MELLITUS CLINICAL TRIALS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的总体目标是选择最适合用于T1D受试者干预研究的代谢测试。需要确定进行试验的最佳条件。这些选择的重要考虑因素包括了解测试的可变性以及测试对检测细胞功能变化的敏感度。同样重要的是，选择在大型临床试验背景下实际进行的测试。在1型糖尿病的临床试验中，选择什么细胞功能指标作为主要结果取决于在临床试验环境中进行试验的实际情况与科学有效性的需要之间的平衡。虽然单独禁食C-肽很容易做到，并且可能与刺激的C-肽结果有很好的相关性，但它可能不足以检测出治疗的细微效果。在临床诊断后，大多数研究涉及非葡萄糖促分泌剂的刺激C肽反应。欧洲人最常使用的是静脉注射胰高血糖素刺激试验。这种方法的优点是测试时间短(6分钟)，但缺点是会引起一过性恶心。其他人则对液体混合餐(Susta al/Boost)使用C肽反应。虽然这不会引起恶心，但确实需要更多的时间。这项研究是一项多中心、双臂、随机的临床试验。将在两组之间进行比较，主要目的是评估混合餐耐量试验(MMTT)与静脉注射胰高血糖素试验在可靠性方面的差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this study is to select the metabolic test that would be best to use for intervention studies in subjects with T1D. The optimal conditions for the conduct of the test need to be determined. Important considerations for these choices include knowing the variability of the test and how sensitive the test is to detect changes in cell function. Equally important is selecting the test that is practical to conduct in the context of a large clinical trial. The choice of what measure of ?-cell function should be used as a primary outcome in clinical trials of type 1 diabetes depends upon balancing the need for scientific validity with the practical realities of performing the tests in a clinical trial setting. While fasting C-peptide alone is easy to do and may correlate well with stimulated C-peptide results, it may be insufficient to detect subtle effects of therapy. Post-clinical diagnosis, most studies involve a stimulated C-peptide response to non-glucose secretagogues. Europeans have most often used IV glucagon stimulated testing. This has the advantage of being a short test (6 minutes), but the disadvantage of causing transient nausea. Others have used C-peptide responses to a liquid mixed meal (Sustacal/Boost). Though this does not induce nausea, it does require more time. The study is a multi-center, two-arm, randomized clinical trial. Comparisons will be made between the two groups, with the primary objective of assessing the difference in reliability of the mixed meal tolerance test (MMTT) versus the IV glucagon infusion test.