Abstract
Aims/hypothesisThe aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus.MethodsIn this patient-blinded, crossover study, 26 participants with type 1 diabetes mellitus attended two randomised experimental visits: one hypoglycaemic clamp (PG 2.8 ± 0.2 mmol/l, approximate duration 55 min) and one euglycaemic clamp (PG 5.5 mmol/l ± 10%). PG levels were maintained by hyperinsulinaemic glucose clamping. Cognitive functioning was assessed during hypoglycaemia and euglycaemia conditions using a modified version of the digit symbol substitution test (mDSST) and control DSST (cDSST). Simultaneously, regional cerebral blood flow (rCBF) was measured in pre-specified brain regions by six H215O-positron emission tomographies (PET) per session.ResultsWorking memory was impaired during hypoglycaemia as indicated by a statistically significantly lower mDSST score (estimated treatment difference [ETD] −0.63 [95% CI −1.13, −0.14], p = 0.014) and a statistically significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p = 0.013) compared with euglycaemia. During hypoglycaemia, mDSST task performance was associated with increased activity in the frontal lobe regions, superior parietal lobe and thalamus, and decreased activity in the temporal lobe regions (p < 0.05). Working memory activation (mDSST − cDSST) statistically significantly increased blood flow in the striatum during hypoglycaemia (ETD 0.0374% [95% CI 0.0157, 0.0590], p = 0.002).Conclusions/interpretationDuring hypoglycaemia (mean PG 2.9 mmol/l), working memory performance was impaired. Altered performance was associated with significantly increased blood flow in the striatum, a part of the basal ganglia implicated in regulating motor functions, memory, language and emotion.Trial registrationNCT01789593, clinicaltrials.govFundingThis study was funded by Novo Nordisk.
Highlights
Cognitive performance, even during simple tasks, is impaired during acute hypoglycaemia in individuals with type 1 diabetes mellitus [1, 2] and the degree of impairment depends on the level of hypoglycaemia [3]
Working memory was impaired during hypoglycaemia as indicated by a statistically significantly lower mDSST score and a statistically significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p = 0.013) compared with euglycaemia
MDSST task performance was associated with increased activity in the frontal lobe regions, superior parietal lobe and thalamus, and decreased activity in the temporal lobe regions (p < 0.05)
Summary
Even during simple tasks, is impaired during acute hypoglycaemia (plasma glucose [PG]
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