Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

Clementine E. M. Verhulst; Therese W. Fabricius; Giesje Nefs; Roy P. C. Kessels; Frans Pouwer; Steven Teerenstra; Cees J. Tack; Melanie M. Broadley; Peter L. Kristensen; Rory J. McCrimmon; Simon Heller; Mark L. Evans; Ulrik Pedersen-Bjergaard; Bastiaan E. de Galan; Hypo-RESOLVE Consortium

doi:10.2337/dc21-2502

Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

Clementine E. M. Verhulst (Lead / Corresponding author), Therese W. Fabricius, Giesje Nefs, Roy P. C. Kessels, Frans Pouwer, Steven Teerenstra, Cees J. Tack, Melanie M. Broadley, Peter L. Kristensen, Rory J. McCrimmon, Simon Heller, Mark L. Evans, Ulrik Pedersen-Bjergaard, Bastiaan E. de Galan, Hypo-RESOLVE Consortium

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Abstract

Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association.

Research Design and Methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP).

Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c.

Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.

Original language	English
Pages (from-to)	2103-2110
Number of pages	8
Journal	Diabetes Care
Volume	45
Issue number	9
Early online date	25 Jul 2022
DOIs	https://doi.org/10.2337/dc21-2502
Publication status	Published - 1 Sept 2022

Keywords

Hyperinsulinemic-hypoglycemic clamp
cognitive function
PASAT
TAP
diabetes
hypoglycemia
Type 1 diabetes
Type 2 diabetes

ASJC Scopus subject areas

Advanced and Specialised Nursing
Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

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

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10.2337/dc21-2502Licence: CC BY

Final published versionFinal published version, 18 MBLicence: CC BY

Cite this

Verhulst, C. E. M., Fabricius, T. W., Nefs, G., Kessels, R. P. C., Pouwer, F., Teerenstra, S., Tack, C. J., Broadley, M. M., Kristensen, P. L., McCrimmon, R. J., Heller, S., Evans, M. L., Pedersen-Bjergaard, U., de Galan, B. E., & Hypo-RESOLVE Consortium (2022). Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes. Diabetes Care, 45(9), 2103-2110. https://doi.org/10.2337/dc21-2502

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title = "Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes",

abstract = "Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as {"}level 2 hypoglycemia.{"} In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association.Research Design and Methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP).Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c.Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.",

keywords = "Hyperinsulinemic-hypoglycemic clamp, cognitive function, PASAT, TAP, diabetes, hypoglycemia, Type 1 diabetes, Type 2 diabetes",

author = "Verhulst, {Clementine E. M.} and Fabricius, {Therese W.} and Giesje Nefs and Kessels, {Roy P. C.} and Frans Pouwer and Steven Teerenstra and Tack, {Cees J.} and Broadley, {Melanie M.} and Kristensen, {Peter L.} and McCrimmon, {Rory J.} and Simon Heller and Evans, {Mark L.} and Ulrik Pedersen-Bjergaard and {de Galan}, {Bastiaan E.} and {Hypo-RESOLVE Consortium}",

note = "Funding Information: This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460. The JU receives support from the European Union{\textquoteright}s Horizon 2020 research and innovation program and EFPIA and T1D Exchange, JDRF, International Diabetes Federation (IDF), The Leona M. and Harry B. Helmsley Charitable Trust.",

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doi = "10.2337/dc21-2502",

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volume = "45",

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Verhulst, CEM, Fabricius, TW, Nefs, G, Kessels, RPC, Pouwer, F, Teerenstra, S, Tack, CJ, Broadley, MM, Kristensen, PL, McCrimmon, RJ, Heller, S, Evans, ML, Pedersen-Bjergaard, U, de Galan, BE & Hypo-RESOLVE Consortium 2022, 'Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes', Diabetes Care, vol. 45, no. 9, pp. 2103-2110. https://doi.org/10.2337/dc21-2502

TY - JOUR

T1 - Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

AU - Verhulst, Clementine E. M.

AU - Fabricius, Therese W.

AU - Nefs, Giesje

AU - Kessels, Roy P. C.

AU - Pouwer, Frans

AU - Teerenstra, Steven

AU - Tack, Cees J.

AU - Broadley, Melanie M.

AU - Kristensen, Peter L.

AU - McCrimmon, Rory J.

AU - Heller, Simon

AU - Evans, Mark L.

AU - Pedersen-Bjergaard, Ulrik

AU - de Galan, Bastiaan E.

AU - Hypo-RESOLVE Consortium

N1 - Funding Information: This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and T1D Exchange, JDRF, International Diabetes Federation (IDF), The Leona M. and Harry B. Helmsley Charitable Trust.

PY - 2022/9/1

Y1 - 2022/9/1

N2 - Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association.Research Design and Methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP).Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c.Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.

AB - Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association.Research Design and Methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP).Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c.Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.

KW - Hyperinsulinemic-hypoglycemic clamp

KW - cognitive function

KW - PASAT

KW - TAP

KW - diabetes

KW - hypoglycemia

KW - Type 1 diabetes

KW - Type 2 diabetes

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U2 - 10.2337/dc21-2502

DO - 10.2337/dc21-2502

M3 - Article

C2 - 35876660

SN - 0149-5992

VL - 45

SP - 2103

EP - 2110

JO - Diabetes Care

JF - Diabetes Care

IS - 9

ER -

Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Hypoglycaemia - REdefining SOLutions for better liVEs (Hypo-RESOLVE) (Joint with Stichting Katholieke Universiteit, King's College London, Medizinische Universitat Graz and 19 others)

Cite this

Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Hypoglycaemia - REdefining SOLutions for better liVEs (Hypo-RESOLVE) (Joint with Stichting Katholieke Universiteit, King's College London, Medizinische Universitat Graz and 19 others)

Cite this