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Open Access 01-03-2018 | Article

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

Authors: Michael Gejl, Albert Gjedde, Birgitte Brock, Arne Møller, Eelco van Duinkerken, Hanne L. Haahr, Charlotte T. Hansen, Pei-Ling Chu, Kirstine L. Stender-Petersen, Jørgen Rungby

Published in: Diabetologia | Issue 3/2018

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 H₂ ¹⁵O-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.

Available only for authorised users

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Title: Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial
Authors: Michael Gejl
Albert Gjedde
Birgitte Brock
Arne Møller
Eelco van Duinkerken
Hanne L. Haahr
Charlotte T. Hansen
Pei-Ling Chu
Kirstine L. Stender-Petersen
Jørgen Rungby
Publication date: 01-03-2018
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 3/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-017-4502-1

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

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Trial registration

Funding

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Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Trial registration

Funding

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