Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes

McCarthy, Olivia, Pitt, Jason, Churm, Rachel, Dunseath, Gareth J, Jones, Charlotte, Bally, Lia, Nakas, Christos T, Deere, Rachel, Eckstein, Max L, Bain, Stephen C, Moser, Othmar and Bracken, Richard M 2020. Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes. BMJ Open Diabetes Research and Care 8 (1) , e001577. 10.1136/bmjdrc-2020-001577

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Abstract

Introduction This study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D). Research design and methods Thirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05. Results Cardiorespiratory and counterregulatory hormone responses, whole-body fuel use and perception of fatigue during exercise were similar under conditions of hypoglycemia and euglycemia (BG 3.5±0.3 vs 5.8±1.1 mmol/L, respectively p<0.001). HypoEx was associated with greater adenosine salvage pathway activity (5’-methylthioadenosine, p=0.023 and higher cysteine and methionine metabolism), increased utilization of glucogenic amino acids (glutamine, p=0.021, alanine, aspartate and glutamate metabolism and homoserine/threonine, p=0.045) and evidence of enhanced β-oxidation (lower carnitine p<0.001, higher long-chain acylcarnitines). Conclusions Exposure to acute hypoglycemia during exercise potentiates alterations in subclinical indices of metabolic stress at the level of the metabolome. However, the physiological responses induced by dynamic physical exercise may mask the symptomatic recognition of mild hypoglycemia during exercise in people with T1D, a potential clinical safety concern that reinforces the need for diligent glucose management. Trial registration number DRKS00013509. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Centre for Trials Research (CNTRR)
Publisher:	BMJ Publishing Group
ISSN:	2052-4897
Date of First Compliant Deposit:	27 September 2023
Date of Acceptance:	10 March 2019
Last Modified:	18 Oct 2023 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/162789

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