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.
N1 - Funding Information: Acknowledgments. The authors thank the Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark; Stine Tving Kjøller, Charlotte Hansen, Pernille Banck-Petersen, and Rikke Carstensen for assisting as research nurses and Charlotte Pietraszek and Susanne Månsson for preparation of blood and other practicalities during the clamp in Denmark; Stephanie A. Amiel from the department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, U.K. for discussing the data and providing feedback on the manuscript; Namam Ali, Josephin Zielmann, and Pieter Drijver from the Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands, for testing cognitive function; and Evertine Abbink and Linda Drenthen from the Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands, and Karin Saini, Marjolein Eybergen, Emma Lenssen, and Esther Eggenhuizen from the Radboudumc Technology Center Department of Clinical Studies, Radboud University Medical Centre, Nijmegen, the Netherlands, for assistance during the clamps in the Netherlands. Funding. 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. Duality of Interest. P.L.K. has received speakers fees from Sanofi A/S, Novo Nordisk A/S, and AstraZeneca A/S. B.E.d.G. has received research support from Novo Nordisk. U.P.-B. has served on advisory boards for AstraZeneca, Bristol-Myers Squibb, Sanofi, Novo Nordisk, and Zealand Pharma and has received lecture fees from AstraZeneca, Bristol-Myers Squibb, Sanofi, and Novo Nordisk. No other potential conflicts of interest relevant to this article were reported. Author Contributions. C.E.M.V., T.W.F., G.N., R.P.C.K., C.J.T., U.P.-B., and B.E.d.G. designed the study. C.E.M.V. and T.W.-F. performed the experiments and collected data. C.E.M.V. Publisher Copyright: © 2022, American Diabetes Association Inc.. All rights reserved.
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) hypoglyce-mic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglyce-mic-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 cor-rect 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 ontheTAPWorkingMemorytaskby2.0±5.5(allP < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA 1c. 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) hypoglyce-mic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglyce-mic-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 cor-rect 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 ontheTAPWorkingMemorytaskby2.0±5.5(allP < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA 1c. 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.
UR - http://www.scopus.com/inward/record.url?scp=85137136471&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/dc21-2502
DO - https://doi.org/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 -