Association between recent real-life exposure to hypoglycaemia and cognitive function during hypoglycaemia in people with type 1 diabetes: Findings from the Hypo-RESOLVE clamp study

Aims: 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. Materials and Methods: 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. Results: 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 _1c and hypoglycaemia awareness status in linear regression analyses. Conclusions: 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.