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

doi:10.2337/dc21-2502

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 - Sept 2022

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10.2337/dc21-2502Licence: CC BY

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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. (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

@article{c9a62cec030f47dbace4d40ad5110b64,

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.",

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}",

note = "{\textcopyright} 2022 by the American Diabetes Association.",

year = "2022",

month = sep,

doi = "10.2337/dc21-2502",

language = "English",

volume = "45",

pages = "2103--2110",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

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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 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

PY - 2022/9

Y1 - 2022/9

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.

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 -