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^*, 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

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

5 Downloads (Pure)

Abstrakt

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.

Originalsprog	Engelsk
Tidsskrift	Diabetes Care
Vol/bind	45
Udgave nummer	9
Sider (fra-til)	2103-2110
ISSN	0149-5992
DOI	https://doi.org/10.2337/dc21-2502
Status	Udgivet - 1. sep. 2022

Bibliografisk note

Funding information:
This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (which receives support from the European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations and T1D Exchange, JDRF, International Diabetes Federation, and The Leona M. and Harry B. Helmsley Charitable Trust) under grant agreement no. 777460.

Dokumenter og links

10.2337/dc21-2502

Open access versionForlagets udgivne version, 18 MB

Citationsformater

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

@article{e6288cf70a2146f1b5843ac27e3b7087,

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} and {Hypo-RESOLVE consortium}",

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

year = "2022",

month = sep,

day = "1",

doi = "10.2337/dc21-2502",

language = "English",

volume = "45",

pages = "2103--2110",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "9",

}

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, bind 45, nr. 9, s. 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 (which receives support from the European Union’s Horizon 2020 research and innovation program and European Federation of Pharmaceutical Industries and Associations and T1D Exchange, JDRF, International Diabetes Federation, and The Leona M. and Harry B. Helmsley Charitable Trust) under grant agreement no. 777460.

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.

U2 - 10.2337/dc21-2502

DO - 10.2337/dc21-2502

M3 - Journal article

C2 - 35876660

VL - 45

SP - 2103

EP - 2110

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 9

ER -

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

Abstrakt

Bibliografisk note

Dokumenter og links

Fingeraftryk

Citationsformater