Standardization of C-Peptide and HbA1C (UC4)

描述(申请人提供)：糖尿病是一种慢性疾病，以胰岛素缺乏、高血糖和眼睛、肾脏、周围神经、心脏和血管并发症的高风险为特征。这种疾病在美国非常普遍，影响着近2600万人。1993年完成的具有里程碑意义的为期九年的糖尿病控制和并发症试验(DCCT)最终表明，通过改善血糖控制，通过一系列HbA1c测定评估，1型糖尿病患者发生和发展慢性并发症的风险可以大大降低。近年来，HbA1c测量标准化变得更加重要，原因有两个；第一，随着糖尿病发病率的上升，该测试的使用越来越多；第二，该测试最近被推荐用于糖尿病诊断。此外，FDA还利用HbA1c的改善作为糖尿病新疗法批准的结果衡量标准。因此，除了糖尿病治疗的临床目标范围外，现在迫切需要接近正常范围的精确度和精密度。DCCT确定了另一项关键实验室测量在1型糖尿病中的重要性。C-肽是在血清中发现的一种稳定的、可检测到的胰岛素的非功能性裂解产物。C-肽的测量用于监测接受外源性胰岛素治疗的糖尿病患者的内源性胰岛素产生。越来越多的证据，包括来自DCCT研究的数据，表明1型糖尿病患者即使保持较低水平的内源性胰岛素产生，也与显著减少糖尿病并发症有关。因此，现在用高度灵敏和标准化的方法测量C肽水平对于准确实施和解释临床试验以确定能够 在发病时逆转或延缓疾病的发展。随着更多的干预措施和药物组合被测试用于临床，改善、协调和标准化C肽测量在未来可能更加重要。本申请适用于继续实施HbA1c和C-肽的标准化计划。 公共卫生相关性：HbA1c作为糖尿病血糖控制的标志物，以及最近作为一种诊断工具的重要性已经得到证实。这个拟议的项目将改进HbA1c的测量，以实现最佳的临床和诊断用途。保存1型糖尿病患者的胰岛β细胞功能已被认为是延缓发病时疾病进展和治疗干预的重要目标。准确、标准化的C肽测量将有助于实现这一目标，也是本应用的主题。

DESCRIPTION (provided by applicant): Diabetes mellitus is a chronic disorder characterized by insulin deficiency, hyperglycemia, and high risk for development of complications of the eyes, kidneys, peripheral nerves, heart and blood vessels. The disease is highly prevalent, affecting nearly 26 million people in the U.S. The landmark nine-year Diabetes Control and Complications Trial (DCCT), completed in 1993, showed conclusively that the risk for development and progression of the chronic complications in patients with type 1 diabetes mellitus could be dramatically reduced with improved blood glucose control as assessed by serial HbA1c determinations. HbA1c measurement standardization has become even more important in recent years for two reasons; first, there is increased use of the test, with rising rates of diabees and second, the test has recently been recommended for use in diabetes diagnosis. In addition, the FDA has utilized improvements in HbA1c as an outcome measure for approval of new therapies for diabetes. Thus there is now a critical need for accuracy and precision near the normal range in addition to the clinical target range for diabetes treatment. DCCT established the importance of another key laboratory measurement in type 1 diabetes. C-peptide is a stable and detectable non-functional cleavage product of insulin found in serum. Measurement of C-peptide is used to monitor endogenous insulin production in people with diabetes who are receiving exogenous insulin as therapy. There is increasing evidence, including data from the DCCT study, that preservation of even a low level of endogenous insulin production in people with type 1diabetes is associated with significantly fewer diabetes complications. Measuring C-peptide levels with highly sensitive and standardized methods is therefore important now to accurately implement and interpret clinical trials to identify therapeutic interventions capable of reversing or delaying progression of the disease at onset. Improving, harmonizing, and standardizing C-peptide measurements could be even more important in the future as additional interventions and combination of agents are tested for clinical benefit. This application if for continued implementation of standardization programs for both HbA1c and C-peptide. PUBLIC HEALTH RELEVANCE: The importance of HbA1c as a marker of glycemic control in diabetes mellitus, and more recently as a diagnostic tool, has been established. This proposed project will improve the measurement of HbA1c for optimal clinical and diagnostic use. Preservation of beta cell function in type 1diabetes has been identified as an important goal in delaying progression of the disease at onset and also for therapeutic intervention. Accurate, standardized measurement of C- peptide will aid in this goal and is also the subject of this application.