• Kathryn L Gwizdala, David P Ferguson, Jeffery Kovan, Vera Novak, and Matthew B Pontifex.
• Department of Kinesiology, Michigan State University, 126E IM Sports Circle, East Lansing, MI, 48824-1049, USA.
• Metab Brain Dis. 2021 Aug 1; 36 (6): 1289-1303.

AbstractA growing number of investigations are exploring the utility of intranasal insulin as a means of mitigating cognitive decline. However, as a basic tenant of dementia prevention programs is increasing physical activity, it is essential to obtain a preliminary assessment of the safety profile of combining intranasal insulin with physical activity; to ensure that undue risks are not incurred. Utilizing a randomized double-blind placebo-controlled design, a sample of 116 non-diabetic, fasted college-aged adults were randomly assigned to receive a dose of 0-to-120 IU of NovoLog (Insulin Aspart) before being randomized to 20 min of exercise or sitting control condition. The safety of intranasal insulin was assessed by examining the incidence of potential symptoms of hypoglycemia and changes in peripheral blood glucose. The efficacy of a combination therapeutic approach was assessed using behavioral measures of inhibition and sustained attention alongside neuroelectric indices of attentional engagement. The frequency of symptoms reported following administration of intranasal insulin were not observed to interact with exercise so as to make their occurrence any more or less prominent, nor was the frequency observed to relate to the dose of intranasal insulin. However, doses of intranasal insulin of 100 IU or more were observed to result in a 7-fold increase in the likelihood of a level 1 hypoglycemic event for those individuals in the exercise condition. This study provides preliminary evidence to suggest that exercise is not associated with an increase in risk when combined with lower doses of intranasal insulin.Clinical trial registration The trial is registered at ClinicalTrials.gov, number NCT04292535.© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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