The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19

Whyte, Martin; Vas, Prashanth; Heiß, Christian; Feher, Michael

doi:10.1016/j.diabres.2020.108217

Cited by 27 publications

(39 citation statements)

References 15 publications

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“…It remains unclear whether diabetes drove such excess risk independently from confounders, including its complications and comorbidities. It is conceivable that patients with diabetes experienced a worse COVID-19 outcome because of multiple organ damage due to micro- and macrovascular disease [9] , [10] . On the other side, whether the impact of diabetes on COVID-19 outcome depends on glucose control is less appreciated.…”

Section: Introductionmentioning

confidence: 99%

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration

Fadini

Morieri

Boscari

et al. 2020

Diabetes Research and Clinical Practice

174

168

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We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. Methods: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in NorthEast Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. Results: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newlydiagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newlydiagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. Conclusion: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.

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Section: Introductionmentioning

confidence: 99%

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration

Fadini

Morieri

Boscari

et al. 2020

Diabetes Research and Clinical Practice

174

168

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“…CVD in aging is associated to endothelial dysfunction (EnD) ( O'Rourke and Nichols, 2005 ; Santhanam et al, 2008 ; Ungvari et al, 2019 ) which may be partly reversed through increased bioavailability of nitric oxide (NO). EnD is also a hallmark of diseases such as atherosclerosis, hypertension and diabetes and may be an important pathophysiological element of COVID-19 disease ( Chen and Li, 2020 ; Guzik et al, 2020 ; Whyte et al, 2020 ). Preclinical and clinical evidence shows that vasodilation is importantly mediated by endothelium-dependent NO ( Crecelius et al, 2011 ; Diehl et al, 2011 ; Donato et al, 2011 ; Manicam et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Arginase inhibition by (−)-Epicatechin reverses endothelial cell aging

Garate‐Carrillo

Navarrete‐Yanez

Ortiz-Vilchis

et al. 2020

European Journal of Pharmacology

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Endothelial dysfunction (EnD) occurs with aging and endothelial nitric oxide (NO) production by NO synthase (NOS) can be impaired. Low NO levels have been linked to increased arginase (Ar) activity as Ar competes with NOS for L-arginine. The inhibition of Ar activity can reverse EnD and (−)-epicatechin (Epi) inhibits myocardial Ar activity. In this study, through in silico modeling we demonstrate that Epi interacts with Ar similarly to its inhibitor Norvaline (Norv). Using in vitro and in vivo models of aging, we examined Epi and Norv-inhibition of Ar activity and its endothelium-protective effects. Bovine coronary artery endothelial cells (BCAEC) were treated with Norv (10 μM), Epi (1 μM) or the combination (Epi + Norv) for 48 h. Ar activity increased in aged BCAEC, with decreased NO generation. Treatment decreased Ar activity to levels seen in young cells. Epi and Epi + Norv decreased nitrosylated Ar levels by ~25% in aged cells with lower oxidative stress (~25%) (dihydroethidium) levels. In aged cells, Epi and Epi + Norv restored the eNOS monomer/dimer ratio, protein expression levels and NO production to those of young cells. Furthermore, using 18 month old rats 15 days of treatment with either Epi (1 mg/kg), Norv (10 mg/kg) or combo, decreased hypertension and improved aorta vasorelaxation to acetylcholine, blood NO levels and tetra/dihydribiopterin ratios in cultured rat aortic endothelial cells. In conclusion, results provide evidence that inhibiting Ar with Epi reverses aged-related loss of eNOS function and improves vascular function through the modulation of Ar and eNOS protein levels and activity.

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“…Its consumption leads to a local increase of angiotensin-II, causing vasoconstriction and cytokines release through endothelial activation. Furthermore, endothelial cell dysfunction and microthrombi formation caused by COVID-19 is further worsened from pre-existing microangiopathy associated with poorly controlled diabetes [ 22 ]. Lastly, ACE2 pathway imbalances can also lead to β-cell dysfunction in the pancreas resulting in more hyperglycemia and worse vasculopathy and coagulopathy [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…The injury is directly related to the levels of glycated hemoglobin (HbA1c) and the presence of other microvascular complications such as diabetic neuropathy, retinopathy, and nephropathy. This entity has been described as a "diabetic lung" and can predispose to increased COVID-19 severity [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes is associated with increased risk of critical respiratory illness in patients COVID-19 in a community hospital

Shrestha¹,

Charkviani²,

Musurakis³

et al. 2021

Obesity Medicine

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Background Type 2 diabetes (T2D) is the leading non-communicable disease worldwide and is associated with several microvascular and macrovascular complications. Individuals with T2D are more prone to acquiring selected types of infections and are more susceptible to complications due to these infections. This study aimed to evaluate the relationship between T2D and COVID-19 in the community setting. Methods This was a single-center retrospective analysis that included 147 adult patients with laboratory-confirmed COVID-19 admitted to a community hospital. Demographics, medical history, symptoms and signs, laboratory findings, complications during the hospital course, and treatments were collected and analyzed. The Kaplan-Meier method was used to describe the probability of intubation in patients with T2D as compared with patients without T2D. The hazard ratio for intubation in the survival analysis was estimated using a bivariable Cox proportional-hazards model. Results Of 147 patients, 73 (49.7%) had a history of T2D. Patients with T2D had higher requirement of ICU admission (31.5% vs 12.2%; p=.004), higher incidence of ARDS (35.6% vs 16.2%, p=.007), higher rates of intubation (32.9% vs 12.2%, p=0.003), and higher use neuromuscular blocking agents (23.3% vs 9.5%, p=.02). In the survival analysis at 28 days of follow-up, patients with T2D showed an increased hazard for intubation (HR 3.00; 95% CI, 1.39 to 6.46). Conclusion In our patient population, patients with COVID-19 and T2D showed significantly higher ARDS incidence and intubation rates. The survival analysis also showed that after 28 days of follow-up, patients with T2D presented an increased risk for shorter time to intubation.

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The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19

Abstract: Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. This may be driven by direct endothelial cell entry by

Cited by 27 publications

References 15 publications

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration

Arginase inhibition by (−)-Epicatechin reverses endothelial cell aging

Type 2 diabetes is associated with increased risk of critical respiratory illness in patients COVID-19 in a community hospital

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