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

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

doi:10.1007/s00125-017-4502-1

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

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

^*Corresponding author for this work

Department of Clinical Medicine

10 Citations (Scopus)

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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.govFunding: This study was funded by Novo Nordisk.

Original language	English
Journal	Diabetologia
Volume	61
Issue number	3
Pages (from-to)	551–561
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-017-4502-1
Publication status	Published - 1 Mar 2018

Keywords

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetesFinal published version, 961 KBLicence: CC BY

Cite this

@article{db853d6001894e05b9de1f246d1771e4,

title = "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.govFunding: This study was funded by Novo Nordisk.",

keywords = "Clinical diabetes, Hypoglycaemia, Imaging (MRI/PET/other), Insulin therapy",

author = "Michael Gejl and Albert Gjedde and Birgitte Brock and Arne M{\o}ller and {van Duinkerken}, Eelco and Haahr, {Hanne L.} and Hansen, {Charlotte T.} and Chu, {Pei Ling} and Stender-Petersen, {Kirstine L.} and J{\o}rgen Rungby",

year = "2018",

month = mar,

day = "1",

doi = "10.1007/s00125-017-4502-1",

language = "English",

volume = "61",

pages = "551–561",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "3",

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TY - JOUR

T1 - Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes

T2 - a randomised, crossover trial

AU - Gejl, Michael

AU - Gjedde, Albert

AU - Brock, Birgitte

AU - Møller, Arne

AU - van Duinkerken, Eelco

AU - Haahr, Hanne L.

AU - Hansen, Charlotte T.

AU - Chu, Pei Ling

AU - Stender-Petersen, Kirstine L.

AU - Rungby, Jørgen

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.govFunding: This study was funded by Novo Nordisk.

AB - 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.govFunding: This study was funded by Novo Nordisk.

KW - Clinical diabetes

KW - Hypoglycaemia

KW - Imaging (MRI/PET/other)

KW - Insulin therapy

U2 - 10.1007/s00125-017-4502-1

DO - 10.1007/s00125-017-4502-1

M3 - Journal article

C2 - 29188338

AN - SCOPUS:85035323723

SN - 0012-186X

VL - 61

SP - 551

EP - 561

JO - Diabetologia

JF - Diabetologia

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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