Glycemic Variability in Diabetes Increases the Severity of Influenza

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diab...

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Autores principales:	Rebecca J. Marshall, Pornthida Armart, Katina D. Hulme, Keng Yih Chew, Alexandra C. Brown, Philip M. Hansbro, Conor J. Bloxham, Melanie Flint, Katharina Ronacher, Helle Bielefeldt-Ohmann, Linda A. Gallo, Kirsty R. Short
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	blood glucose diabetes influenza Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e7526e11425e4113be3ebc0f2d499ad6
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spelling	oai:doaj.org-article:e7526e11425e4113be3ebc0f2d499ad62021-11-15T15:57:02ZGlycemic Variability in Diabetes Increases the Severity of Influenza10.1128/mBio.02841-192150-7511https://doaj.org/article/e7526e11425e4113be3ebc0f2d499ad62020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02841-19https://doaj.org/toc/2150-7511ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.Rebecca J. MarshallPornthida ArmartKatina D. HulmeKeng Yih ChewAlexandra C. BrownPhilip M. HansbroConor J. BloxhamMelanie FlintKatharina RonacherHelle Bielefeldt-OhmannLinda A. GalloKirsty R. ShortAmerican Society for Microbiologyarticleblood glucosediabetesinfluenzaMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	blood glucose diabetes influenza Microbiology QR1-502
spellingShingle	blood glucose diabetes influenza Microbiology QR1-502 Rebecca J. Marshall Pornthida Armart Katina D. Hulme Keng Yih Chew Alexandra C. Brown Philip M. Hansbro Conor J. Bloxham Melanie Flint Katharina Ronacher Helle Bielefeldt-Ohmann Linda A. Gallo Kirsty R. Short Glycemic Variability in Diabetes Increases the Severity of Influenza
description	ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.
format	article
author	Rebecca J. Marshall Pornthida Armart Katina D. Hulme Keng Yih Chew Alexandra C. Brown Philip M. Hansbro Conor J. Bloxham Melanie Flint Katharina Ronacher Helle Bielefeldt-Ohmann Linda A. Gallo Kirsty R. Short
author_facet	Rebecca J. Marshall Pornthida Armart Katina D. Hulme Keng Yih Chew Alexandra C. Brown Philip M. Hansbro Conor J. Bloxham Melanie Flint Katharina Ronacher Helle Bielefeldt-Ohmann Linda A. Gallo Kirsty R. Short
author_sort	Rebecca J. Marshall
title	Glycemic Variability in Diabetes Increases the Severity of Influenza
title_short	Glycemic Variability in Diabetes Increases the Severity of Influenza
title_full	Glycemic Variability in Diabetes Increases the Severity of Influenza
title_fullStr	Glycemic Variability in Diabetes Increases the Severity of Influenza
title_full_unstemmed	Glycemic Variability in Diabetes Increases the Severity of Influenza
title_sort	glycemic variability in diabetes increases the severity of influenza
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e7526e11425e4113be3ebc0f2d499ad6
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Glycemic Variability in Diabetes Increases the Severity of Influenza

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