Department of Diabetes, School of Life Course Sciences, King's College London, London, U.K.
King's College Hospital NHS Foundation Trust, London, U.K.
Diabetes Care. 2021 Feb;44(2):533-540. doi: 10.2337/dc20-1250. Epub 2020 Dec 16.
Impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor for severe hypoglycemia (SH) and is associated with atypical responses to hypoglycemia in brain regions involved in arousal, decision making, and memory. Whether restoration of hypoglycemia awareness alters these responses is unknown. We sought to investigate the impact of awareness restoration on brain responses to hypoglycemia.
Twelve adults with T1D and IAH underwent pseudocontinuous arterial spin labeling functional MRI during a hypoglycemic clamp (5-2.6 mmol/L) before and after a hypoglycemia avoidance program of structured education (Dose Adjustment for Normal Eating), specialist support, and sensor-augmented pump therapy (Medtronic MiniMed 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared pre- and postintervention using predefined region-of-interest analysis of the thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and hippocampus.
Postintervention, Gold and Clarke scores fell (6.0 ± 1.0 to 4.0 ± 1.6, = 0.0002, and 5.7 ± 1.7 to 3.4 ± 1.8, = 0.0008, respectively), SH rates reduced (1.5 ± 2 to 0.3 ± 0.5 episodes per year, = 0.03), hypoglycemic symptom scores increased (18.8 ± 6.3 to 27.3 ± 12.7, = 0.02), and epinephrine responses did not change ( = 0.2). Postintervention, hypoglycemia induced greater increases in ACC CBF ( = 0.01, peak voxel coordinates [6, 40, -2]), while thalamic and OFC activity did not change.
Increased blood flow is seen within brain pathways involved in internal self-awareness and decision making (ACC) after restoration of hypoglycemia awareness, suggesting partial recovery of brain responses lost in IAH. Resistance of frontothalamic networks, involved in arousal and emotion processing, may explain why not all individuals with IAH achieve awareness restoration with education and technology alone.
1 型糖尿病（T1D）患者的低血糖意识受损（IAH）是严重低血糖（SH）的主要危险因素，并且与涉及觉醒、决策和记忆的脑区对低血糖的异常反应有关。恢复低血糖意识是否会改变这些反应尚不清楚。我们试图研究意识恢复对低血糖时脑反应的影响。
12 名 T1D 合并 IAH 的成年人在接受结构化教育（剂量调整正常进食法）、专科支持和传感器增强型泵治疗（美敦力 MiniMed 640G）的低血糖回避方案前后，接受了假性连续动脉自旋标记功能 MRI 检查。通过对丘脑、前扣带皮层（ACC）、眶额皮层（OFC）和海马的预先定义的感兴趣区分析，比较了干预前后的低血糖脑血流（CBF）反应。
干预后，Gold 和 Clarke 评分降低（6.0±1.0 降至 4.0±1.6， = 0.0002，5.7±1.7 降至 3.4±1.8， = 0.0008），SH 发生率降低（1.5±2 降至 0.3±0.5 次/年， = 0.03），低血糖症状评分升高（18.8±6.3 升至 27.3±12.7， = 0.02），而肾上腺素反应没有变化（ = 0.2）。干预后，低血糖引起的 ACC CBF 增加更大（ = 0.01，峰值体素坐标[6,40,-2]），而丘脑和 OFC 活动没有变化。
在恢复低血糖意识后，与内部自我意识和决策相关的脑通路中的血流增加（ACC），表明在 IAH 中失去的脑反应部分恢复。参与觉醒和情绪处理的额-丘脑网络的抗性可能解释了为什么并非所有 IAH 患者仅通过教育和技术就能实现意识恢复。
