Svensson Cecilie H, Fabricius Therese W, Verhulst Clementine, Tack Cees J, Kristensen Peter L, de Galan Bastiaan E, Pedersen-Bjergaard Ulrik
Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark.
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Diabetes Obes Metab. 2025 Oct;27(10):5455-5463. doi: 10.1111/dom.16587. Epub 2025 Jul 11.
Cognitive decline during hypoglycaemia poses a risk for severe hypoglycaemia among people with type 1 diabetes, as it may compromise the ability to self-treat and recover. Antecedent hypoglycaemia has been associated with blunted counterregulatory responses to subsequent hypoglycaemia, but whether hypoglycaemia-induced cognitive dysfunction is subject to such a process of habituation is unclear. We investigated the association between recent real-life exposure to hypoglycaemia recorded by continuous glucose monitoring (CGM) and cognitive function during a hypoglycaemic clamp.
Forty-two people with type 1 diabetes were given open intermittently scanned CGM (Freestyle Libre 1®) to record real-life hypoglycaemia for a week before participating in a hyperinsulinaemic-euglycaemic-hypoglycaemic clamp (mean ± SD) (2.8 ± 0.1 mmol/L). We assessed cognitive function at baseline and during hypoglycaemia using four validated tests: Paced Auditory Serial Addition Test (PASAT) and three subtasks of Test of Attentional Performance (TAP)-Alertness, Verbal Flexibility, and Working Memory.
Hypoglycaemia exposure (glucose <3.9 mmol/L) in the week before the clamp averaged 5.8 (3.1-8.8) events/week. In response to hypoglycaemia during the clamp, cognitive function declined for all cognitive function tests (all p < 0.01). No associations were identified between exposure to CGM-recorded hypoglycaemia prior to the clamp and changes in cognitive function during the clamp procedure, when adjusting for sex, age, diabetes duration, HbA and hypoglycaemia awareness status in linear regression analyses.
Our findings indicate that recent real-life CGM-recorded hypoglycaemia is not associated with cognitive decline during clamped hypoglycaemia in people with type 1 diabetes. This suggests that cognitive decline during hypoglycaemia is not susceptible to habituation.
低血糖期间的认知能力下降会给1型糖尿病患者带来严重低血糖风险，因为这可能会损害自我治疗和恢复的能力。先前的低血糖与对后续低血糖的反调节反应减弱有关，但低血糖诱导的认知功能障碍是否会经历这样一种习惯化过程尚不清楚。我们研究了通过连续血糖监测（CGM）记录的近期现实生活中低血糖暴露与低血糖钳夹期间认知功能之间的关联。
42名1型糖尿病患者在参加高胰岛素-正常血糖-低血糖钳夹（平均±标准差）（2.8±0.1 mmol/L）之前，接受了开放式间歇性扫描CGM（Freestyle Libre 1®），以记录一周的现实生活中的低血糖情况。我们在基线和低血糖期间使用四项经过验证的测试评估认知功能：听觉连续加法测试（PASAT）以及注意力表现测试（TAP）的三个子任务——警觉性、语言灵活性和工作记忆。
钳夹前一周的低血糖暴露（血糖<3.9 mmol/L）平均为5.8（3.1 - 8.8）次/周。在钳夹期间对低血糖的反应中，所有认知功能测试的认知功能均下降（所有p<0.01）。在进行线性回归分析时，调整性别、年龄、糖尿病病程、糖化血红蛋白和低血糖意识状态后，未发现钳夹前CGM记录的低血糖暴露与钳夹过程中认知功能变化之间存在关联。
我们的研究结果表明，近期现实生活中CGM记录的低血糖与1型糖尿病患者在钳夹低血糖期间的认知能力下降无关。这表明低血糖期间的认知能力下降不易受到习惯化的影响。
