Alternative Biomarkers of Hyperglycemia in ADVANCE

 描述(申请人提供)：高血糖的非传统血浆标志物作为短期血糖控制措施、HbA1c的潜在辅助指标或当HbA1c不可靠或不切实际时替代HbA1c的措施，在糖尿病治疗中越来越受到临床的关注。然而，几乎没有数据支持它们的使用。目的：比较非传统的高血糖标志物和标准方法(糖化血红蛋白和空腹血糖)，以告知它们在2型糖尿病患者治疗中的价值。我们将1)评估和比较作为主要微血管和大血管结局和死亡危险因素的非传统血糖标志物和标准标志物的预后价值；2)描述它们对血糖控制改善的反应。设计和方法：我们将测量7000个储存的生物样本中的一组高血糖的非传统标记物，这些样本来自一项已完成的2型糖尿病随机临床试验，即糖尿病和血管疾病中的作用：Preterax和Diamicron对照评估(ADVANCE)试验。我们还将在基线和一年后再次采集血液的参与者的子样本中进行重复测量。我们将完成一系列流行病学分析，以调查非传统血糖标志物与临床结果的相关性，并将这些结果与HbA1c和空腹血糖的观察结果进行比较。我们将具体评估和比较标准和非传统高血糖标志物的预后价值，并将确定可能的风险阈值与微血管和大血管预后的关系。我们将量化高血糖的非传统标记物的一年变化以及它们在严格的血糖控制下的变化(试验干预)。意义：尽管在许多情况下，HbA1c被认为是血糖控制的次佳指标，但关于替代高血糖标志物的实用性的数据很少。这项研究将挑战当前的临床实践范式，并告知非传统的高血糖标志物是否与HbA1c和空腹血糖一起在临床实践中发挥作用。这项研究的结果将直接与 糖尿病患者管理的临床实践和信息策略。

 DESCRIPTION (provided by applicant): Nontraditional plasma markers of hyperglycemia are of increasing clinical interest in diabetes care as measures of short-term glycemic control, potential adjuncts to HbA1c, or alternatives to HbA1c when HbA1c is unreliable or impractical. However, there is little data to support their use. Aims: To compare nontraditional markers of hyperglycemia to standard measures (HbA1c and fasting glucose) to inform their value in the management of patients with type 2 diabetes. We will 1) evaluate and compare the prognostic value of nontraditional glycemic markers to standard markers as risk factors for major microvascular and macro-vascular outcomes and death; and 2) characterize their response to improved glycemic control. Design and Methods: We will measure a panel of nontraditional markers of hyperglycemia in >7,000 stored biospecimens from a completed randomized clinical trial of type 2 diabetes, the Action in Diabetes and VAscular disease: preterax and diamicroN Controlled Evaluation (ADVANCE) Trial. We will also conduct repeat measurements in a subsample of participants with blood collections at baseline and again at one year. We will complete a series of epidemiological analyses to investigate the associations of nontraditional glycemic markers with clinical outcomes during 10 years of follow-up (during the trial and extended observational follow- up) and compare these results to those observed for HbA1c and fasting glucose. We will specifically evaluate and compare the prognostic value of standard and nontraditional markers of hyperglycemia and we will characterize possible risk thresholds in the associations with microvascular and macro-vascular outcomes. We will quantify one-year change in the nontraditional markers of hyperglycemia and their change in response to tight glycemic control (trial intervention). Significance: Although it is recognized that HbA1c is a suboptimal measure of glucose control in a number of settings, data on the utility of alternative markers of hyperglycemia are scarce. This research will challenge current paradigms in clinical practice and inform whether nontraditional markers of hyperglycemia have a role alongside HbA1c and fasting glucose in clinical practice. Results of this study will have direct relevance to clinical practice and inform strategies for the management of patients with diabetes.