Does Variation in Mean Red Cell Age Impact HbA1c Interpretation?

糖尿病退伍军人并发症的预防在很大程度上取决于血糖和血糖的评估 HbA1c，一种衡量血红蛋白(Hb)在红葡萄酒寿命内暴露于平均血糖水平的指标 血细胞(RBC)是最依赖的血糖控制指标。然而，关键之一是 HbA1c解释中的假设，即在 患有糖尿病和红细胞正常的人，最近被证明是无效的。使用更精确的生物素 标记法表明，在其他正常人中，红细胞存活率具有显著的异质性。那里 红细胞存活率的足够差异是否足以改变AS测量的HbA1c对血糖控制的估计 高达30%，这引发了人们的担忧，即HbA1c值在一个重要的数字中并不意味着相同的事情 病人的数量。这将需要一种方法来评估何时以及如何修改HbA1c解释。 尽管有明确的证据表明，人与人之间的红细胞存活率存在差异，但将这种差异归因于 个体之间的差异取决于回答几个简单的问题，这些问题令人惊讶地仍然存在 未回答：红细胞存活率在个体内是否随时间稳定，以及血糖是否可控 会影响它的稳定性。因此，拟议研究的目标是界定这些特征。第一 特定目标检验了非糖尿病受试者和受试者的平均红细胞年龄是稳定的假设 糖尿病患者血糖控制稳定。第二个具体目标是检验平均红细胞年龄将 最初血糖控制较差的糖尿病患者，在接受治疗后没有变化 稳定，改善血糖控制8个月。为了实现这两个目标，红细胞存活和平均血液 在10名无糖尿病的受试者中，血糖将分两次测定，间隔至少四个月。 糖尿病和血糖控制稳定的受试者，以及最多15名糖尿病受试者的初始血糖水平较低 对照，以便随后在改善血糖控制的情况下重新研究10名受试者。RBC的存活率将会是 使用相同的新型生物素RBC标记结合平均血糖测定 持续的血糖监测。 HbA1c是长期监测血糖控制和预测糖尿病的最有价值的临床试验。 糖尿病并发症风险是每年做出的数十万项临床决定的依据 患有糖尿病的退伍军人。拟议的研究，通过进一步定义RBC生存稳定性发展所必需的 因此，一种新的HbA1c解释方法有可能极大地支持 退伍军人事务部的使命是减轻糖尿病及其并发症的负担。

Prevention of complications in veterans with diabetes depends heavily on assessment of blood glucose and HbA1c, a measure of the exposure of hemoglobin (Hb) to average blood glucose over the lifespan of a red blood cell (RBC), is the test most heavily relied upon as a glycemic control indicator. However, one of the key assumptions in HbA1c interpretation, namely that there is a narrow range of red blood cell (RBC) survival in people with diabetes and normal RBCs, has recently been shown to not be valid. Use of a more precise biotin label method demonstrates substantial heterogeneity of RBC survival among otherwise normal people. There is sufficient variation in RBC survival to alter the estimate of glycemic control from measured HbA1c by as much as 30% which introduces concern that HbA1c values do not mean the same thing in a significant number of patients. This will necessitate a means to assess when and how to modify HbA1c interpretation. Although the evidence is clear that there is variation in RBC survival among people, attributing this variation to differences between individuals depends on answering several simple questions which surprisingly remain unanswered: whether RBC survival is stable over time within an individual and whether blood glucose control affects its stability. Therefore, the goal of the proposed studies is to define these characteristics. The first Specific Aim tests the hypothesis that mean RBC age is stable in subjects without diabetes and in subjects with diabetes at stable glycemic control. The second Specific Aim tests the hypothesis that mean RBC age will not change in subjects with diabetes studied initially in poor glycemic control, and again after being treated to stable, improved glycemic control for >8 months. To accomplish the two aims, RBC survival and mean blood glucose will be determined at two times separated by at least four months in 10 subjects without diabetes, 10 subjects with diabetes and stable glycemic control, and up to 15 subjects with diabetes in initial poor glycemic control in order to re-study 10 subjects subsequently in improved glycemic control. The RBC survival will be measured using the same novel biotin RBC label in conjunction with mean glucose determination by continuous glucose monitoring. HbA1c is the most highly valued clinical test for long term monitoring of glycemic control and the prediction of diabetes complications risk is relied upon for hundreds of thousands of clinical decisions made every year in veterans with diabetes. The proposed studies, by further defining RBC survival stability necessary to develop a new approach to HbA1c interpretation, therefore has the potential to dramatically support the Department of Veterans Affairs in its mission to reduce the burden of diabetes and its complications.