Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes

Ohara, Makoto; Nagaike, Hiroe; Goto, Satoshi; Fukase, Ayako; Tanabe, Yuki; Tomoyasu, Masako; Yamamoto, Takakazu; Hayashi, Toshiyuki; Fukui, Tetsuya; Hirano, Tsutomu

doi:10.1016/j.diabres.2018.02.017

Cited by 40 publications

(38 citation statements)

References 51 publications

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“…® with previous observations that a key outcome of glycemic variability is the overproduction of reactive oxygen species, which, in turn, drives increased endothelial production of inflammatory mediators (35,36). Indeed, in the present study, the increased production of proinflammatory mediators under the variable condition was observed both in vivo and in vitro, and this was associated with more severe influenza.…”

Section: Diabetes and Influenzasupporting

confidence: 91%

Glycemic Variability in Diabetes Increases the Severity of Influenza

Marshall

Armart

Hulme

et al. 2020

mBio

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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: Diabetes and Influenzasupporting

confidence: 91%

Glycemic Variability in Diabetes Increases the Severity of Influenza

Marshall

Armart

Hulme

et al. 2020

mBio

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“…Apart from hyperglycemia itself, glycemic variability is also considered to be related to disturbed hormones and oxidative stress. Studies have reported that glycemic variability was correlated to oxidative stress and erythrocyte membrane stability [24], and improvement in glycemic variability reduced oxidative stress [25]. Based on this evidence, we suspect a potential association between glycemic variability and the development of malignancies through hormonal pathways and oxidative stress in people without diabetes.…”

Section: Introductionmentioning

confidence: 69%

Glycemic variability and subsequent malignancies among the population without diabetes

Kobayashi

Noto

Takahashi

et al. 2020

Diabetes Research and Clinical Practice

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“…This mechanism may be due to the fact that the use of a GLP-1-RA affected oxidative stress and vascular endothelial function characteristics. Another possible reason is that glycemic control was better in patients treated with dulaglutide added on conventional therapy and possibly related to an improvement in glucose variability as reported by some studies (47).…”

Section: Discussionmentioning

confidence: 89%

“…A previous research (47) evidenced that the reduction of FPG and the improvement of glycemic variability is correlated to the reduction of oxidative stress on vascular endothelial.…”

Section: Discussionmentioning

confidence: 90%

Efficacy of dulaglutide to improve Vascular Health indexes in subjects with Type 2 Diabetes: A Randomized Trial

Tuttolomondo

Cirrincione²,

Casuccio³

et al. 2020

Preprint

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Background: Recent cardiovascular outcome trials have shown significant reductions of major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Adjunctive surrogates for cardiovascular risk more recently validated by some studies (23,24) are arterial stiffness and endothelial function indexes. No randomized trials have yet addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damageAims: A randomized trial to once-weekly dulaglutide (1.5 mg) added to traditional antidiabetic treatment compared to traditional treatment alone to evaluate some metabolic efficacy endpoints and surrogate vascular efficacy endpoints such as endothelial function and arterial stiffness indexes.Methods: Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c was 9.5% or less on stable doses of up to two oral glucoselowering drugs with or without basal insulin therapy were eligible. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness indexes (pulse wave velocity and augmentation index) and endothelial function index (reactive hyperemia index) were evaluated at baseline and at a three-month and nine-month examination visit. At each visit (at 3 and 9 month follow-up) were also evaluated glycemic variables such as fasting plasma glucose (FPG), HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride. Results: at a three month follow up subjects treated with dulaglutide in comparison with subjects treated with conventional therapy showed significantly lower serum levels of FBG and significantly lower percentage of HBa1c. At a 9 month follow up subjects treated with dulaglutide in comparison with control subjects treated with conventional therapy showed a significant lowering of diastolic blood pressure, BMI, mean total serum cholesterol, LDL cholesterol, FPGa significantly lower percentage of HBa1C and PWV and higher mean RHI values.Discussion: These findings are consistent with previous studies indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.

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Improvements of ambient hyperglycemia and glycemic variability are associated with reduction in oxidative stress for patients with type 2 diabetes

Abstract: Improvements in glucose metabolism, including FPG and daily and day-to-day glucose variability, were all correlated with reduced oxidative stress for patients with T2DM.

Cited by 40 publications

References 51 publications

Glycemic Variability in Diabetes Increases the Severity of Influenza

Glycemic Variability in Diabetes Increases the Severity of Influenza

Glycemic variability and subsequent malignancies among the population without diabetes

Efficacy of dulaglutide to improve Vascular Health indexes in subjects with Type 2 Diabetes: A Randomized Trial

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