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

Clementine E. M. Verhulst (Lead / Corresponding author), 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

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)
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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.

    Original languageEnglish
    Pages (from-to)2103-2110
    Number of pages8
    JournalDiabetes Care
    Issue number9
    Early online date25 Jul 2022
    Publication statusPublished - 1 Sept 2022


    • Hyperinsulinemic-hypoglycemic clamp
    • cognitive function
    • PASAT
    • TAP
    • diabetes
    • hypoglycemia
    • Type 1 diabetes
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Advanced and Specialised Nursing
    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism


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