Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection

Abstract

IntroductionStress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19.MethodsIn a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission.ResultsPatients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders.ConclusionsIn patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap—a cross-sectional study

“…The study protocol was designed before the COVID-19 pandemic; thus, COVID-19 cases were excluded from the present study. In addition, the roles of chronic, acute, and acute-on-chronic hyperglycaemia as risk factors for dysregulated inflammatory responses in COVID-19 have been described elsewhere ( 17 , 18 ).…”

“…Moreover, transient hyperglycaemia has been shown to induce inflammatory endothelial activation ( 15 ) and enhance leukocyte cytokine release in preclinical studies ( 16 ), contrasting with the impaired cytokine responses seen in chronic hyperglycaemia as in type 2 diabetes ( 11 ). While chronic hyperglycaemia (as seen in type 2 diabetes), acute hyperglycaemia, and acute-on-chronic hyperglycaemia have been linked to dysregulation of the immune host response in COVID-19 pneumonia ( 17 , 18 ), these associations have been sparingly explored in non-COVID-19 CAP.…”

Newly detected diabetes during the COVID-19 pandemic: What have we learnt?

“…Comparing admissions with DKA in the preceding three years to those during the first 12 months of the pandemic analysis showed the DKA admissions in people with type 2 diabetes. Similarly, DKA admissions increased in people newly presenting with diabetes (not known if type 1 or type 2 diabetes); 57% [48] , [49] , [50*] , [51*] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] higher during the first wave and 61% [52–70] higher during the second wave. These higher numbers of DKA cases were observed across all age categories.…”

“…However, observational data would suggest that the biggest driver of dysglycaemia and altered presentations of diabetes during the pandemic are related to this hyperinflammatory stress response and the insulin resistance that ensues. Stress hyperglycaemia in the absence of a diagnosis of diabetes is an established independent risk factor for poorer outcomes in patients hospitalised with COVID-19 [57] . In a small cohort of paediatric DKA cases studied during the pandemic, those with SARS-COV-2 were more likely to present with indices of higher insulin resistance than those in DKA without SARS-COV-2 infection [58] .…”

Profiling of circulating serum exosomal microRNAs in elderly patients with infectious stress hyperglycaemia

“…Inflammation is one of the main causes of stress hyperglycaemia, especially infectious stress hyperglycaemia (ISH), which are able to predictable deterioration to septic shock, and the fatality rate is as high as 70%-80%. 1,11 Moreover, 95% of sepsis patients have abnormal glucose metabolism and severe IR, and the exact molecular mechanism is not yet clear. 1 Intensive insulin therapy (IIT) is currently the main method for the treatment of stress hyperglycaemia.…”