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, Volume 9 (Number 4). Article number e94915. doi:10.1371/journal.pone.0094915 ISSN 1932-6203.

Preview

PDF WRAP_journal.pone.0094915.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution. Download (1610Kb) | Preview

Request Changes to record.

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
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Anoxemia, Insulin resistance, Oxidative stress
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	14 April 2014
Dates:	Date Event 14 April 2014 Published
Volume:	Volume 9
Number:	Number 4
Article Number:	Article number e94915
DOI:	10.1371/journal.pone.0094915
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	27 December 2015
Date of first compliant Open Access:	27 December 2015
Funder:	Linde Gas Therapeutics, Eli Lilly and Company, London Clinic, Smiths Medical, Deltex Medical (Firm), Rolex Foundation, Association of Anaesthetists of Great Britain and Ireland (AAGBI), Intensive Care Society (Great Britain) (ICS), Halley Stewart Trust, Great Britain. Department of Health (DoH), Medical Research Council (Great Britain) (MRC), University of Southampton. Faculty of Medicine

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads