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A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study

Lookup NU author(s): Dr Daniel West

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background and aims: Approximately 25% of people with Type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia, the cause of which is unknown. We recently proposed that impaired awareness of hypoglycaemia develops through Habituation; a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counter regulatory hormonal responses to hypoglycaemia in a rodent model of impaired awareness of hypoglycaemia following introduction of a novel stress stimulus [high intensity exercise]; referred to as Dishabituation. In this study we sought to further test this hypothesis by examining whether a single episode of high intensity exercise would amplify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had impaired awareness of hypoglycaemia (assessed by Gold score ≥4, Modified Clarke score≥4 or DAFNE hypoglycaemia awareness rating 2 or 3). Methods: In this, randomised, cross-over study (ISRCTN15236211) twelve participants with type 1 diabetes and IAH were recruited. Individuals were randomised to one episode of high intensity exercise (4 x 30 s cycle sprints [2 min recovery] at 150% of max Watts achieved during VO2peak assessment) or rest (control). The following day they underwent a 90-minute hyperinsulinaemic hypoglycaemic clamp study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing [4-choice reaction time and digit symbol substitution test]. Each intervention and subsequent clamp study was separated by at least 2-weeks. Results: All participants [6 male and 6 female, age 19-54 years, median (IQR) duration of type 1 diabetes 24.5 years (11.75), HbA1c 56 (19) mmol/mol (7.3%)] completed the study (both interventions and 2 clamps). In comparison to the control study, a single episode of high intensity exercise led to a 29% increase in the adrenaline response (control vs. high intensity exercise) [mean (SEM); 2286.5 (343.1) vs. 2953.8 (384.9) pmol/l; a significant increase in total symptom scores (Edinburgh Hypoglycaemia scale: 24.25 +/- 2.96 vs. 27.5 +/- 3.9; p<0.05), and a significant prolongation of 4-choice reaction time [591.8 +/- 22.5 vs. 659.9 +/- 39.86 ms; p<0.01] during equivalent hypoglycaemia induced the following day. Conclusion: These findings are consistent with the hypothesis that impaired awareness of hypoglycaemia develops in people with type 1 diabetes as a habituated response and that introduction of a novel stressor can restore, at least partially, the adapted counterregulatory response hormonal, symptomatic and cognitive responses to hypoglycaemia. High intensity exercise may therefore represent a novel therapeutic intervention for people with impaired awareness of hypoglycaemia.


Publication metadata

Author(s): Farrell CM, McNeilly AD, Fournier P, Jones T, Hapca SM, West DJ, McCrimmon RJ

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2020

Volume: 63

Pages: 853-863

Print publication date: 01/04/2020

Online publication date: 15/01/2020

Acceptance date: 25/11/2019

Date deposited: 20/01/2020

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer Berlin Heidelberg

URL: https://doi.org/10.1007/s00125-019-05076-5

DOI: 10.1007/s00125-019-05076-5


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