Does Variation in Mean Red Cell Age Impact HbA1c Interpretation?

平均红细胞年龄的变化是否会影响 HbA1c 的解释？

• 批准号: 7792923
• 负责人: ROBERT Maynard COHEN
• 金额: --
• 依托单位: CINCINNATI VA MEDICAL CENTER RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7792923
• 关键词: Address; Affect; Area; Biotin; Blood Glucose; Cell Aging; Cell Survival; Characteristics; Clinical; Complications of Diabetes Mellitus; Dependence; Development; Diabetes Mellitus; Disease; Ensure; Erythrocytes; Exhibits; Frequencies; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Hemoglobin; Heterogeneity; Individual; Label; Laboratories; Longevity; Measurement; Measures; Methods; Mission; Monitor; Organ; Patients; Population; Population Heterogeneity; Prevention; Property; Relative (related person); Reporting; Reproducibility; Research; Risk; Role; Source; Techniques; Testing; Time; Uncertainty; Variant; Veterans; blood glucose regulation; cell age; clinical decision-making; glucose monitor; glycemic control; improved; novel; novel strategies; prevent; public health relevance; research clinical testing

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Prevention of complications of diabetes depends heavily on the assessment of blood glucose control which in turn depends on interpretation of HbA1c results. Our laboratory has demonstrated that one of the key assumptions in HbA1c interpretation, that there is a narrow range of red blood cell (RBC) survival in people with diabetes and normal RBCs, is not valid: Rather the heterogeneity of RBC survival among otherwise normal people can introduce dramatic differences in HbA1c sufficient to alter clinical decisions. The proposed studies are directed toward understanding the stability of RBC survival, a key determinant of HbA1c, and whether RBC survival is a source of variation in the dependence of HbA1c on mean blood glucose which in turn underlies hundreds of thousands of clinical decisions made every year in veterans with diabetes.

描述（由申请人提供）： 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 HbA1c 的评估，HbA1c 是衡量红细胞 (RBC) 生命周期内血红蛋白 (Hb) 与平均血糖的接触程度的指标，是最受依赖的血糖控制指标。然而，HbA1c 解释的关键假设之一，即糖尿病患者和红细胞正常的红细胞 (RBC) 存活范围狭窄，最近被证明是无效的。使用更精确的生物素标记方法证明了正常人群中红细胞存活率的显着异质性。 RBC 存活率存在足够的差异，可将测量的 HbA1c 对血糖控制的估计值改变多达 30%，这引起了人们的担忧，即 HbA1c 值在相当多的患者中并不意味着同样的事情。这就需要一种方法来评估何时以及如何修改 HbA1c 解释。尽管证据明确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，而这些问题令人惊讶地仍未得到解答：个体内红细胞存活率是否随着时间的推移保持稳定，以及血糖控制是否会影响其稳定性。因此，拟议研究的目标是定义这些特征。第一个具体目标测试了以下假设：在没有糖尿病的受试者和血糖控制稳定的糖尿病受试者中，平均红细胞年龄是稳定的。第二个具体目标检验了以下假设：对于最初在血糖控制不佳的情况下研究的糖尿病受试者，以及在接受稳定、改善的血糖控制超过 8 个月的治疗后，平均红细胞年龄不会发生变化。为了实现这两个目标，将在 10 名无糖尿病受试者、10 名患有糖尿病且血糖控制稳定的受试者以及最多 15 名最初血糖控制不佳的糖尿病受试者中两次测定红细胞存活率和平均血糖，每次间隔至少四个月，以便重新研究随后血糖控制改善的 10 名受试者。将使用相同的新型生物素红细胞标记结合连续血糖监测测定平均血糖来测量红细胞存活率。 HbA1c 是长期监测血糖控制最有价值的临床测试，糖尿病退伍军人每年做出的数十万个临床决策都依赖于糖尿病并发症风险的预测。因此，拟议的研究通过进一步定义开发新的 HbA1c 解释方法所需的红细胞生存稳定性，有可能极大地支持退伍军人事务部减轻糖尿病及其并发症负担的使命。 公共卫生相关性： 糖尿病并发症的预防在很大程度上取决于血糖控制的评估，而血糖控制的评估又取决于对 HbA1c 结果的解释。我们的实验室已经证明，HbA1c 解释的关键假设之一，即糖尿病患者和正常红细胞 (RBC) 的红细胞 (RBC) 存活率范围较窄，这一假设是无效的：相反，正常人群中红细胞 (RBC) 存活率的异质性可能会导致 HbA1c 的巨大差异，足以改变临床决策。拟议的研究旨在了解红细胞存活率的稳定性（HbA1c 的关键决定因素），以及红细胞存活率是否是 HbA1c 对平均血糖依赖性的变异来源，而平均血糖又是每年为患有糖尿病的退伍军人做出的数十万个临床决策的基础。