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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
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Caudwell Xtreme Everest Research Group (Including: Siervo, Mario, Riley, Heather L., Fernandez, Bernadette O., Leckstrom, Carl A., Martin, Daniel S., Mitchell, Kay, Levett, Denny Z. H., Montgomery, Hugh E., Mythen, Monty G., Grocott, Michael P. W. and Feelisch, Martin). (2014) Effects of prolonged exposure to hypobaric hypoxia on oxidative stress, inflammation and gluco-insular regulation : the not-so-sweet price for good regulation. PLoS One, 9 (4). pp. 1-10. e94915. doi:10.1371/journal.pone.0094915
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Official URL: http://dx.doi.org/10.1371/journal.pone.0094915
Abstract
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 (SpO2) and venous blood lactate concentrations were determined.
Results:
SpO2 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.
| Item Type: | Journal Article | ||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||
| Divisions: | Faculty of Science > Centre for Systems Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Insulin resistance, Oxidative stress | ||||||||
| Journal or Publication Title: | PLoS One | ||||||||
| Publisher: | Public Library of Science | ||||||||
| ISSN: | 1932-6203 | ||||||||
| Official Date: | 14 April 2014 | ||||||||
| Dates: |
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| Volume: | 9 | ||||||||
| Number: | 4 | ||||||||
| Number of Pages: | 10 | ||||||||
| Page Range: | pp. 1-10 | ||||||||
| Article Number: | e94915 | ||||||||
| DOI: | 10.1371/journal.pone.0094915 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | BOC Health Care, Eli Lilly and Company, London Clinic, Smiths Medical, Deltex Medical (Firm), Montres Rolex S.A., Association of Anaesthetists of Great Britain and Ireland (AAGBI), Intensive Care Society (Great Britain) (ICS), Halley Stewart Trust, Medical Research Council (Great Britain) (MRC), University of Southampton | ||||||||
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