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Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress, Inflammation and Gluco-Insular Regulation: The Not-So-Sweet Price for Good Regulation

Lookup NU author(s): Dr Mario Siervo



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


Objectives: The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses.Methods: After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC; 5,300 m) over 13 days. Of these, 14 ascended higher, with 8 reaching the summit (8,848 m). Assessments were conducted at baseline, during ascent to EBC, and 1, 6 and 8 week(s) thereafter. Changes in body weight and indices of gluco-insular control were measured (glucose, insulin, C-Peptide, homeostasis model assessment of insulin resistance [HOMA-IR]) along with biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE), inflammation (Interleukin-6 [IL-6]) and counter-regulatory hormones (glucagon, adrenalin, noradrenalin). In addition, peripheral oxygen saturation (SpO(2)) and venous blood lactate concentrations were determined.Results: SpO(2) fell significantly from 98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained stable, insulin and C-Peptide concentrations increased by >200% during the last 2 weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with increases in markers of oxidative stress (4-HNE) and inflammation (IL-6). Lactate levels progressively increased during ascent and remained significantly elevated until week 8. Subjects lost on average 7.3 kg in body weight.Conclusions: Sustained hypoxemia is associated with insulin resistance, whose magnitude correlates with the degree of oxidative stress and inflammation. The role of 4-HNE and IL-6 as key players in modifying the association between sustained hypoxia and insulin resistance merits further investigation.

Publication metadata

Author(s): Siervo M, Riley HL, Fernandez BO, Leckstrom CA, Martin DS, Mitchell K, Levett DZH, Montgomery HE, Mythen MG, Grocott MPW, Feelisch M, Caudwell Xtreme Everest Research Group

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2014

Volume: 9

Issue: 4

Print publication date: 14/04/2014

Acceptance date: 21/03/2014

Date deposited: 22/08/2014

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0094915


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