Elucidating the heterogeneity of impaired awareness of hypoglycaemia in type 1 diabetes

1项目概要/摘要 2 1型糖尿病（T1D）患者的低血糖意识受损（IAH）与 3例存在生理反调节和低血糖症状反应缺陷， 4导致严重低血糖（SH）风险增加。教育和技术，例如 5混合闭环（HCL）胰岛素输送减少了低血糖暴露，但恢复了 6、意识是可变的。用于筛选和衡量意识的现有工具，如Clarke 7和Gold评分缺乏检测CGM中低血糖意识变化的敏感性 8“电子意识”时代。因此，我们需要构建和验证更高级的 9工具，可以客观地评估IAH。该项目旨在了解 10有助于使用HCL成功恢复低血糖意识， 11名T1D和IAH患者，并验证评估意识变化所需的工具 12号状态为了解决电话中的具体问题，我们提出了5个子研究。 13 1.研究1：了解T1D患者对实验性低血糖的生理反应 14与NAH和切换到混合闭环对这些响应随时间的影响。 十五两研究2：确定是否通过转换为 16最先进的混合闭环技术可以恢复生理反应， T1D和IAH患者中17例随时间推移的实验性低血糖 18 3.研究3：确定低血糖特定教育（HARPdoc）是否能够解决 19种与IAH相关的认知和信念可能是低血糖的障碍 20避免（即使有技术）导致进一步减少低血糖暴露 T1D和IAH患者对低血糖的生理反应改善 22 4.研究4：确定与生理反应恢复相关的因素 23低血糖我们将参与者分为恢复（R-IAH）、部分（P-IAH）或 24例持续性（S-IAH）基于生理变化的低血糖意识受损 钳夹研究中25例（肾上腺素和症状）对实验性低血糖的反应， 26调查与每个类别相关的人口统计学、血糖和行为因素。 27 5.研究5：确定正常、P-IAH和S-IAH反应的诊断临界值， 28个实验性低血糖，用于当前的自我报告问卷和一种名为 我们还将使用HypoMETRICS应用程序来探索差异 30之间的"生理"和"技术"的低血糖意识。

1 Project Summary / Abstract 2 Impaired Awareness of Hypoglycemia (IAH) in people with type 1 diabetes (T1D) is associated 3 with defects in physiological counterregulatory and symptom responses to hypoglycemia as 4 leading to increased risk of severe hypoglycemia (SH). Education and technologies such as 5 hybrid closed loop (HCL) insulin delivery reduce hypoglycemia exposure, but restoration of 6 awareness is variable. Existing tools for screening and measuring awareness, such as Clarke 7 and Gold scores lack sensitivity to detect changes in hypoglycemia awareness in the CGM 8 era of “electronic awareness”. Therefore, we need to construct and validate more advanced 9 tools that can objectively assess IAH. This project seeks to understand the factors that 10 contribute to the successful restoration of awareness of hypoglycemia using HCL in 11 those with T1D and IAH and validate the tools required to assess changes in awareness 12 status. To address the specific questions in the call, we propose 5 sub-studies. 13 1. Study 1: To understand the physiological responses to experimental hypoglycemia in T1D 14 with NAH and the impact of a switch to hybrid closed loop on these responses over time. 15 2. Study 2: To determine if reducing exposure to biochemical hypoglycemia by switching to 16 state of the art hybrid closed loop technology can restore physiological responses to 17 experimental hypoglycemia over time in individuals with T1D and IAH 18 3. Study 3: To determine if hypoglycaemia specific education (HARPdoc) that addresses 19 cognitions and beliefs associated with IAH that are possible barriers to hypoglycemia 20 avoidance (even with technology) leads to further reductions in hypoglycemia exposure 21 and improved physiological responses to hypoglycemia in individuals with T1D and IAH 22 4. Study 4: To determine the factors associated with restoration of physiological responses 23 to hypoglycemia. We will categorise participants into Restored (R-IAH), Partial ( P-IAH) or 24 Sustained (S-IAH) impaired awareness of hypoglycemia based on changes in physiological 25 (epinephrine and symptom) responses to experimental hypoglycemia in clamp studies and 26 investigate demographic, glycemic and behavioural factors associated with each category. 27 5. Study 5: To determine diagnostic cut-offs for Normal, P-IAH and S-IAH responses to 28 experimental hypoglycemia for current self-report questionnaires and a novel tool named 29 the HypoMETRICS app. We will also use the HypoMETRICS app to explore differences 30 between “physiological” and “technological” awareness of hypoglycemia.