Dataset Information

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

ABSTRACT:

Aims/hypothesis

The 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.

Methods

In 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.

Results

Working 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/interpretation

During 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 registration

NCT01789593, clinicaltrials.gov FUNDING: This study was funded by Novo Nordisk.

SUBMITTER: Gejl M

PROVIDER: S-EPMC6448973 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

Gejl Michael M Gjedde Albert A Brock Birgitte B Møller Arne A van Duinkerken Eelco E Haahr Hanne L HL Hansen Charlotte T CT Chu Pei-Ling PL Stender-Petersen Kirstine L KL Rungby Jørgen J

Diabetologia 20171129 3

<h4>Aims/hypothesis</h4>The 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.<h4>Methods</h4>In 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 ...[more]

PMID: 29188338

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Project description:PurposePhysical activity (PA) breaks during school lessons have been suggested as a promising strategy to improve working memory performance in children and adolescents. There is a lack of studies investigating the underlying physiological mechanisms of PA on cognition, especially among adolescents. This study aimed to investigate the effects of different types of short frequent PA on adolescents' cognitive task-related changes in cerebral blood flow in the prefrontal cortex (PFC) and working memory performance compared to prolonged sitting.MethodsIn this randomized crossover study, adolescents visited the laboratory on three different occasions for 80-minute sessions of prolonged sitting interrupted by four breaks for three minutes of simple resistance training (SRA), step-up at a pre-determined pace (STEP), or remaining seated (SOCIAL). Before and after each session, cognitive task-related changes in cerebral blood flow (oxygenated-hemoglobin, Oxy-Hb) during working memory tasks (1-, 2-, 3-back tests) were measured using functional near-infrared spectroscopy in the PFC. Accuracy and reaction time were derived from the working memory tasks. Linear mixed-effect models were used to analyze the data.ResultsA total of 17 students participated (mean age 13.6 years, 11 girls). Significant time x condition interactions were noted for Oxy-Hb in the most demanding working memory task (3-back), with a decrease following prolonged sitting in the SOCIAL condition compared to both the SRA (β 0.18, 95% CI 0.12, 0.24) and the STEP (β 0.11, 95% CI 0.05, 0.17). This was observed in parallel with improvements in reaction time following SRA (β -30.11, 95% CI -59.08, -1.13) and STEP (β -34.29, 95% CI -69.22, 0.63) although this was only significant for the SRA and no improvements in the SOCIAL condition.ConclusionWe found that short frequent PA breaks during prolonged sitting among adolescents can prevent the decrease in cognitive task-related changes in cerebral blood flow that occur following prolonged sitting. This was observed simultaneously with improvements in working memory, indicating that changes in cerebral blood flow could be one factor explaining the effects on working memory. Future studies should investigate the efficacy of implementing these PA breaks in schools.Trial registrationRetrospectively registered on 21/09/2020, ClinicalTrial (NCT04552626).

Dataset Information

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Trial registration

Publications

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

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