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

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posted on 25.07.2022, 13:39 authored by 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, the Hypo-RESOLVE consortium


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”. The present study 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 controls 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 proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased the mean 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 cut-off value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes. 


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.