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的评估， HbA1c是血红蛋白（Hb）在红细胞寿命期间暴露于平均血糖的量度。 血细胞（RBC）是最依赖的血糖控制指标。然而，其中一个关键 HbA1c解释中的假设，即红细胞（RBC）存活率的范围很窄， 糖尿病和正常红细胞的人，最近被证明是无效的。使用更精确的生物素 标记方法显示在其他正常人中RBC存活的实质异质性。那里 RBC存活率的变化足以改变HbA1c测量值对血糖控制的估计， 高达30%的人担心HbA1c值在很大程度上并不意味着相同的事情 病人。这将需要一种方法来评估何时以及如何修改HbA1c解释。 尽管有证据表明，人与人之间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， 未解答：个体内红细胞存活是否随时间推移而稳定以及血糖是否得到控制 影响其稳定性。因此，拟议研究的目标是定义这些特征。第一 特定目的检验了无糖尿病受试者和受试者的平均RBC年龄稳定的假设 血糖控制稳定的糖尿病患者第二个特定目标测试假设平均RBC年龄将 在最初研究的血糖控制不佳的糖尿病受试者中没有变化，并且在治疗后再次发生变化， 稳定、改善血糖控制>8个月。为了实现这两个目标，RBC存活率和平均血液 在10名无糖尿病的受试者中，将在间隔至少4个月的两次测定葡萄糖， 血糖控制稳定的糖尿病受试者和初始血糖控制不佳的糖尿病受试者（最多15例） 控制，以便随后在改善的血糖控制中重新研究10名受试者。RBC存活率将为 使用相同的新型生物素RBC标记结合平均葡萄糖测定进行测量， 连续血糖监测。 HbA1c是长期监测血糖控制和预测 糖尿病并发症风险是每年数十万临床决策的依据， 患有糖尿病的退伍军人拟议的研究，通过进一步定义红细胞存活稳定性， 因此，一种新的HbA1c解释方法有可能极大地支持 退伍军人事务部在其使命，以减少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.