Continuous Glucose Monitoring in Dialysis Patients to Overcome Dysglycemia Trial (CONDOR TRIAL)

项目摘要/摘要 糖尿病(DM)是慢性肾脏疾病(CKD)的主要原因，约占47%， 约39%的美国终末期肾病(ESKD)患者发病和流行。我们出版的 研究表明，低血糖是一种高度普遍的并发症，与更高的死亡风险有关。 糖尿病肾病(DKD)患者。糖尿病血液透析(HD)患者罹患 通过多种途径引起的低血糖，包括1)肾脏糖异生减少，2)代谢受损/ 糖尿病药物的清除，3)共存的并存，4)限制中心内HD食物的获取，以及5)内部 透析后的葡萄糖移位。鉴于低血糖对心血管(CV)健康的不良影响(心律失常， 在非CKD患者中观察到)和心理健康(低血糖恐惧、压力/焦虑) 研究表明，糖尿病HD患者的存活率较低(5年内为35%)，主要是由于心血管疾病的原因，有 一个迫切的未得到满足的需求是确定减轻该人群低血糖并发症的策略。 DKD患者最佳血糖控制的主要障碍之一是缺乏实用的、 经常进行血糖测定的可靠方法。在糖尿病HD患者中，常规指标(自我评估) 监测的血糖[SMBG]，HbA1c)被主要使用，尽管在准确性、便利性、 和间歇性频率。相比之下，连续血糖监测(CGM)是一种方便、自动化的方法 血糖评估方法显示，在非糖尿病患者中，血糖控制有所改善，低血糖发生率降低 CKD试验。而我们在HD患者中的CGM试点数据显示与黄金标准血非常一致 血糖水平和更好地识别低血糖，尚不确定CGM是否可以 改善血糖控制，减少低血糖，优化患者报告的结果。 为了解决这一知识差距，我们提出了这项多PI R01研究，在该研究中，我们旨在进行 平行双臂随机对照试验(RCT)，比较使用Dexcom G6设备的实时CGM与 122名中心HD糖尿病患者12周期间的常规护理(SMBG 4次/天)。我们的初选 目标是确定CGM与常规护理对血糖控制的影响，定义为 在目标血糖范围内的时间(70-180毫克/分升)。我们的主要和探索性次要目标将是 测定CGM对CGM低血糖指数、血糖化标志物(HbA1c、 糖化白蛋白、果糖胺)和患者报告的结果(与健康相关的生活质量、糖尿病 痛苦、低血糖恐惧)。我们还将通过衡量CGM的合规性来评估可行性端点 在患者中实施CGM培训课程的干预期和成功/轻松程度。这首单曲- 中心试点随机对照试验是确定CGM治疗糖尿病HD的可行性、有效性和安全性的关键第一步 它将提供必要的初步数据，为未来大规模、多层次的 中心RCT具有更多的终端、参与者和站点数量。

PROJECT SUMMARY/ABSTRACT Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD), accounting for ~47% and ~39% of US incident and prevalent end‐stage kidney disease (ESKD) patients, respectively. Our published research has shown that hypoglycemia is a highly prevalent complication associated with higher death risk in diabetic kidney disease (DKD) patients. Diabetic hemodialysis (HD) patients are at heightened risk for hypoglycemia via multiple pathways, including 1) decreased renal gluconeogenesis, 2) impaired metabolism/ clearance of DM medications, 3) co-existing comorbidities, 4) limited in-center HD food access, and 5) intra- dialytic glucose shifts. Given the ill effects of hypoglycemia on the cardiovascular (CV) health (arrhythmia, myocardial ischemia) and psychological well-being (hypoglycemia fear, stress/anxiety) observed in non-CKD studies, and the poor survival of diabetic HD patients (<35% over 5 years) largely due to CV causes, there is an urgent unmet need to identify strategies that mitigate low glycemic complications in this population. One of the major barriers to optimal glycemic control in DKD has been the lack of access to a practical, reliable method for frequent glycemic assessment. In diabetic HD patients, conventional metrics (self- monitored blood glucose [SMBG], HbA1c) are dominantly used despite limitations in accuracy, convenience, and intermittent frequency. In contrast, continuous glucose monitoring (CGM) is a convenient, automated glycemic assessment method that has shown improved glycemic control and reduced hypoglycemia in non- CKD trials. While our pilot data of CGM in HD patients shows strong agreement with gold-standard blood glucose levels and superior identification of hypoglycemia, it remains uncertain as to whether CGM can improve glycemic control, reduce hypoglycemia, optimize patient-reported outcomes in this population. To address this knowledge gap, we propose this Multiple-PI R01 study in which we aim to conduct a parallel, two-arm randomized controlled trial (RCT) comparing real-time CGM using Dexcom G6 devices vs. usual care (SMBG 4-times/day) among 122 in-center HD patients with DM over a 12-week period. Our primary objective will be to determine the effects of CGM vs. usual care on glycemic control, defined by percent (%) of time in target glucose range (70-180 mg/dl). Our main and exploratory secondary objectives will be to determine the effects of CGM on CGM-indices of hypoglycemia, blood-based glycemic markers (HbA1c, glycated albumin, fructosamine), and patient-reported outcomes (health-related quality of life, diabetes distress, hypoglycemia fear). We will also evaluate feasibility endpoints by measuring CGM compliance during the intervention period and success/ease of implementing CGM training sessions among patients. This single- center pilot RCT is the critical first step in determining the feasibility, efficacy, and safety of CGM in diabetic HD patients, and it will provide the requisite preliminary data to inform the framework of future large-scale, multi- center corollary RCT’s with an expanded number of endpoints, participants, and sites.