Diabetes and COVID-19: Role of insulin resistance as a risk factor for COVID-19 severity

Abstract

Patients with diabetes are more susceptible to coronavirus disease 2019 (COVID-19), and as a consequence, develop more severe form of disease. This is partly due to a systemic inflammatory state and pro thrombotic milieu seen in metabolic syndrome. In this review, we attempt to explore the pathogenetic links between insulin resistance and COVID-19 disease severity. Insulin resistance is an underlying condition for metabolic syndromes, including type 2 diabetes, which impairs insulin signaling pathways affecting metabolic and cardiovascular homeostasis. A high concentration of circulating insulin shifts the balance to mitogen activated protein kinase (MAPK)-dependent signaling and causes endothelial cell damage. The phosphatidylinositol 3 kinase and MAPK dependent signaling pathways maintain a balance between nitric oxide-dependent vasodilator and endothelin-1 dependent vasoconstriction actions of insulin. Vascular smooth muscle cell dysfunction is responsible for inflammation and blood coagulation leading to microvascular and macrovascular complications in diabetes. Hyperactivity in renin-angiotensin system is implicated in development of islet oxidative stress and subsequent β-cell dysfunction, as it alters the islet blood flow. These deleterious effects of insulin resistance involving altered blood pressure, vascular dysfunction, and inflammation could be associated with increased severity in COVID-19 patients. We conclude that clinical and/or biochemical markers of insulin resistance should be included as prognostic markers in assessment of acute COVID-19 disease.

Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation

“…The benefits of GlyNAC supplementation go well beyond correcting GSH deficiency and OxS as it also improves inflammation, mitochondrial dysfunction, endothelial vascular dysfunction, insulin resistance, genotoxicity, autophagy/mitophagy and muscle strength as reported in human clinical trials [ 31 , 32 ]. This is relevant because similar defects are also reported in patients with COVID-19 [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. Overall, the combination of the findings of this study, and the observations on the potential benefits of GlyNAC supplementation in prior clinical trials suggest a potentially beneficial role for GlyNAC supplementation in COVID-19 infected patients and supports the need for research studies to evaluate the impact of GlyNAC supplementation in COVID-19.…”

Implicazioni cliniche extraglicemiche dell’insulino-resistenza

“…Diversi studi epidemiologici hanno evidenziato che i pazienti affetti da Diabete Mellito di Tipo 2 hanno maggiore suscettibilità alle infezioni da SARS-CoV-2 e sviluppano una malattia più severa [ 19 ]. L’iperinsulinemia nei pazienti insulino-resistenti aumenta l’espressione dell’ Angiotensin Converting Enzyme (ACE2), che rappresenta la porta di ingresso del SARS-CoV-2 nelle cellule, giustificando la maggiore suscettibilità a questo tipo di infezioni nei pazienti diabetici.…”

“…Questi meccanismi giustificherebbero la maggiore severità della malattia nei pazienti insulino-resistenti (Fig. 2 ) [ 19 ].

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The Correlation Between Triglyceride-Glucose Index and SARS-CoV-2 RNA Re-Positive in Discharged COVID-19 Patients

“…[10][11][12] Several previous studies indicated that clinical markers of insulin resistance should be included as prognostic markers in assessment of COVID-19. 13 Studies have shown that patients with insulin resistance may have an increased SARS-CoV-2 viral load, because of insulin increases membrane expression of ACE2, which acts as a dock for the virus to enter cells. 14 But, so far, no previous study has investigated the relationship between TyG index and re-positive of discharged COVID-19 patients.…”