Psychosocial Aspects


Clementine Verhulst, Therese Fabricius, Giesje Nefs, Roy Kessels, Frans Pouwer, Steven Teerenstra, Cees Tack, Melanie Broadley, Peter Kristensen, Rory McCrimmon, Simon Heller, Mark Evans, Ulrik Pedersen-Bjergaard, Bastiaan de Galan

Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes. Diabetes Care. 2022 Sep 1;45(9):2103-2110.

Hypoglycemia is an almost unavoidable side effect of T1D treatment: adults with T1D experience 1 to 2 mild hypoglycemia episodes every week and 40% experience severe hypoglycemia (needing external assistance) annually. Glucose is the main fuel for the brain, but it is not able to produce or store much glucose and is therefor dependent on a continuous supply of glucose. During hypoglycemia (i.e. levels of blood sugar lower than normal), the brain experiences a shortage of glucose, leading to problems with cognition, or even seizures, coma or death. Needless to say, hypoglycemia can have serious effects on daily life. It is debated how low glucose levels need to be to induce cognitive decline. The International Hypoglycemia Study Group (IHSG) stated that glucose levels <3 mmol/L (<54 mg/dL; ‘Level 2 hypoglycemia’) is clinically relevant as these levels have effects on cognitive function. However, not much is known to what extent these effects are affected by (type of) diabetes, diabetes duration, baseline glucose levels, hypoglycemia awareness status, and HbA1c levels. This study, co-authored by Diabeter psychologist Giesje Nefs, aimed to assess the effect of Level 2 hypoglycemia on people with type 1 and type 2 diabetes and compare them with people without diabetes.


In this multicenter intervention study, performed at the Internal Medicine outpatient clinics of Radboud University Medical Center and Nordsjællands Hospital,

  • adults with T1D without impaired awareness of hypoglycemia (IAH; n=26)
  • adults with T1D with IAH (n=21),
  • adults with insulin-treated T2D (n=15)
  • age-matched control subjects (n=32)

underwent hypoglycemic glucose clamps (i.e. artificially generating a hypoglycemic state) and the effect on cognition was assessed.

Key findings:

  • There was no difference in baseline glucose levels between participants with T1D or T2D, which were higher than for control subjects
  • Cognition (% correct answers, reaction time) significantly decreased in the hypoglycemic state (glucose <3.0 mmol/L) for all groups
  • Change in congnition was not dependent on:
    • the presence of diabetes
    • diabetes type
    • awareness status
    • glycemic control (HbA1c)
    • duration of diabetes


Concluding, the authors state

"Altogether, these findings underscore the clinical relevance of avoiding hypoglycemia of this magnitude for the broader population of people with diabetes and support the current classification proposed by the IHSG, in particular with respect to level 2 hypoglycemia" -

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