Alternative Biomarkers of Hyperglycemia in ADVANCE

 描述（由申请人提供）：非传统的高血糖血浆标志物在糖尿病护理中作为短期血糖控制、HbA 1c潜在替代物或HbA 1c不可靠或不切实际时的HbA 1c替代物的指标越来越受到临床关注。然而，很少有数据支持其使用。目的：比较非传统的高血糖标志物与标准指标（HbA 1c和空腹血糖），以了解其在2型糖尿病患者管理中的价值。我们将1）评价和比较非传统血糖标志物与标准标志物作为主要微血管和大血管结局和死亡风险因素的预后价值; 2）描述其对改善血糖控制的反应。设计和方法：我们将在一项已完成的2型糖尿病随机临床试验（糖尿病和Vascular疾病的行动：preterax和diamicroN对照评价（ADVANCE）试验）中，测量超过7，000份储存的生物标本中的一组非传统高血糖标志物。我们还将在基线和第一年再次采血的参与者子样本中进行重复测量。我们将完成一系列流行病学分析，以研究10年随访期间（试验期间和扩展观察性随访期间）非传统血糖标志物与临床结局的相关性，并将这些结果与HbA 1c和空腹血糖观察结果进行比较。我们将专门评估和比较标准和非传统的高血糖标志物的预后价值，我们将描述与微血管和大血管结局相关的可能风险阈值。我们将量化高血糖症非传统标志物的一年变化及其对严格血糖控制（试验干预）的反应。重要性：尽管人们认识到HbA 1c在许多情况下是血糖控制的次优指标，但关于高血糖症替代标志物效用的数据很少。这项研究将挑战目前临床实践中的范式，并告知高血糖症的非传统标志物是否与HbA 1c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关系到 临床实践和告知糖尿病患者的管理策略。

 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.