Influenza Virus and Glycemic Variability in Diabetes: A Killer Combination?

Hulme, Katina D.; Gallo, Linda A.; Short, Kirsty R.

doi:10.3389/fmicb.2017.00861

Cited by 117 publications

(133 citation statements)

References 65 publications

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“…It is well documented that diabetes confers an increased risk for severe influenza, yet the mechanisms that underlie this susceptibility are largely unclear (7). Here, a previously described in vitro model of the epithelial-endothelial respiratory barrier was used along with novel murine models of glycemic variability to provide the first evidence that glycemic variability can increase influenza severity.…”

Section: Discussionmentioning

confidence: 99%

Glycemic Variability in Diabetes Increases the Severity of Influenza

Marshall

Armart

Hulme

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Glycemic Variability in Diabetes Increases the Severity of Influenza

Marshall

Armart

Hulme

et al. 2020

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“…The presence of at least one co-morbidity, mainly cardiovascular diseases, asthma, malignancy and diabetes mellitus, in 71% of hospitalized patients and 31% of outpatients is worrisome especially with recent data on influenza being a trigger for exacerbation of these illnesses and vice versa. Several papers have showed an association between influenza infection and myocardial infarction, chronic obstructive pulmonary disease exacerbations and diabetic crises [18,23,24,27,48,49]. This also means that at least half of the study population were probably at higher risk for severe influenza disease and outcome including death [50].…”

Section: Discussionmentioning

confidence: 99%

“…Given the epidemic nature of the illness, there has been an increasing interest in the burden resulting from its outbreaks in addition to concerns about its association with myocardial infarctions, glycemic variation in diabetic patients, and the exacerbation of other chronic illnesses [1,[18][19][20][21][22][23][24][25][26][27]. While data on the epidemiology and severity of this disease has been primarily obtained from studies in temperate developed countries, developing regions including the MENA region have also begun investigating this burden in their hospitals allowing the formation of more complete global data [28].…”

Section: Introductionmentioning

confidence: 99%

The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience

et al. 2020

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Background: Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon. Methods: A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis.

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“…Insulin resistance (type-2 diabetes, metabolic syndrome) always is associated with a deficient ER signaling in the background [25]. Type-2 diabetes strongly inhibits estrogen regulated innate and adaptive immune functions and alters patient's capacity to resolve inflammation and repair damaged tissue [26].…”

Section: Pre-existing Chronic Diseases Associated With Insulin Resistmentioning

confidence: 99%

Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients

2020

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The presented work summarizes the results of studies underlining the crucial role of estrogen receptor (ER) signaling in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Experimental studies justify that among respiratory virus infected mice, a weaker ER signaling leads to increased morbidity and mortality in both males and females. In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate; it seems to be an ideal prevention and therapy against COVID-19. We should overcome the widespread reluctance to estrogen therapy as we have a unique estrogen formula; conjugated estrogens, or conjugated equine estrogens available under the brand name of Premarin deriving from natural sources. Premarin can exert similar ER upregulative and gene repairing power like endogenous estrogen without any risk for adverse reactions. Premarin is capable of stopping the COVID-19 pandemic.

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Influenza Virus and Glycemic Variability in Diabetes: A Killer Combination?

Cited by 117 publications

References 65 publications

Glycemic Variability in Diabetes Increases the Severity of Influenza

Glycemic Variability in Diabetes Increases the Severity of Influenza

The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience

Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients

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