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Diabetologia. 2018 Mar;61(3):551-561. doi: 10.1007/s00125-017-4502-1. Epub 2017 Nov 29.

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

Author information

1
Department of Biomedicine, Aarhus University, Bartholins Allé 6, Building 1242, 8000, Aarhus C, Denmark. mg@biomed.au.dk.
2
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. mg@biomed.au.dk.
3
Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
4
Department of Clinical Medicine, University of Southern Denmark, Odense, Denmark.
5
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
6
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
7
Department of Biomedicine, Aarhus University, Bartholins Allé 6, Building 1242, 8000, Aarhus C, Denmark.
8
PET-Center, Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark.
9
VU University Medical Centre, Amsterdam, the Netherlands.
10
Pontifícia Universidade Católica, Rio de Janeiro, Brazil.
11
Novo Nordisk A/S, Søborg, Denmark.
12
Novo Nordisk Inc., Plainsboro, NJ, USA.
13
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
14
Department of Endocrinology IC, Bispebjerg University Hospital, Bispebjerg, Copenhagen, Denmark.

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.

KEYWORDS:

Clinical diabetes; Hypoglycaemia; Imaging (MRI/PET/other); Insulin therapy

PMID:
29188338
DOI:
10.1007/s00125-017-4502-1

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