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


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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.

TidsskriftDiabetes Care
Udgave nummer9
Sider (fra-til)2103-2110
StatusUdgivet - 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.


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