TO COMPARE THE RELIABILITY OF MMTT AND IV GLUCAGON STIMULATION TEST

比较 MMTT 和 IV 胰高血糖素刺激试验的可靠性

• 批准号: 7377649
• 负责人: PHILIP RASKIN
• 金额: $ 0.03万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377649
• 关键词: COMPARE; RELIABILITY; MMTT; IV; GLUCAGON

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. A recent consensus workshop evaluated potential surrogate markers such as immune responses to islet cells, HbA1c, and rates of complicatons or hypoglycemia. Each of these potential markers was determined to have limitations. Measures of anti-ilset immune responses have not been shown to correlate with clinical measures. HbA1c is not only an insensitive measure of beta cell secretion, the currently accepted clinical treatment standard for "tight" glucose control confounds the use of HbA1c as an endpoint in clinical trials. In addition, use of rates of complications or hypoglycemia as a primary endpoint would require many years or decades of study. In contrast, direct assessment of residual beta cell function is an appropriate endpoint, as retention of beta cell function in patients with T1D is known to result in improved glycemic control and reduced hypoglycemia, retinopathy, and nephropathy. Endogenous beta cell function or insulin secretion is best measured by determination of C-peptide (which is co-secreted with insulin in a 1:1 molar ratio). Intervention studies over the past few decades have usually used measurement of C-peptide in response to a liquid mixed meal (mixed meal tolerance test; MMTT) or an introvenous bolus of glucagon as indicative of residual beta cell function. However, the relationship between these or other measures of beta cell funtion has not been well studied. In addition, the relative advantages of one measure over another in terms of variability, sensitivity and burden to the subject is unknown. The overall goal of this proposal therefore is to select the metabolic test that would be best to use for intervention studies in subjects with T1D. In addition, 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 beta cell function. Equally important is selecting the test that is practical to conduct in the context of a large clinical trial. In summary, the TrialNet Metabolic Assessment Study comparing the reliabilty of MMTT and IV Glucagon Stimulation Tests in T1D will greatly facilitate the optimal design and implementation of future TrialNet prevention trials. Moreover, the kind and quantity of data that will be derived from the extensive study network will enhance research into the prevention of T1D beyond the realm of TrialNet.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。最近的一个共识研讨会评估了潜在的替代标志物，如对胰岛细胞的免疫反应、HbA1c、并发症或低血糖的发生率。这些潜在的标记物都有其局限性。抗疾病免疫反应的措施尚未显示与临床措施相关。HbA1c不仅是一个对β细胞分泌不敏感的指标，目前公认的“严格”血糖控制的临床治疗标准也混淆了HbA1c作为临床试验终点的使用。此外，使用并发症或低血糖率作为主要终点将需要多年或数十年的研究。相反，直接评估剩余的β细胞功能是一个合适的终点，因为已知T1D患者的β细胞功能保留可以改善血糖控制，减少低血糖、视网膜病变和肾病。内源性β细胞功能或胰岛素分泌最好通过测定c肽（c肽与胰岛素以1:1的摩尔比共分泌）来测定。过去几十年的干预研究通常使用c肽测量对液体混合餐的反应（混合餐耐量试验；MMTT）或静脉注射胰高血糖素作为残余β细胞功能的指示。然而，这些或其他β细胞功能测量之间的关系尚未得到很好的研究。此外，在可变性、敏感性和对主题的负担方面，一种措施相对于另一种措施的相对优势是未知的。因此，本提案的总体目标是选择最适合T1D患者干预研究的代谢测试。此外，还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β细胞功能变化的敏感性。同样重要的是，在大型临床试验的背景下选择可行的试验。综上所述，TrialNet代谢评估研究比较MMTT和IV胰高血糖素刺激试验在T1D中的可靠性，将极大地促进未来TrialNet预防试验的优化设计和实施。此外，从广泛的研究网络中获得的数据种类和数量将加强对TrialNet领域之外的T1D预防的研究。