Hyperglycemia in Covid-19 Infection without Diabetes Mellitus: Association with Inflammatory Markers

ABSTRACT

INTRODUCTION: New onset hyperglycemia is common in patients with severe Covid-19 infection. Cytokine storm due to Covid-19 infection is an important etiology for new-onset hyperglycemia, but factors like direct SARS-CoV-2 induced pancreatic beta-cell failure have also been postulated to play a role. We assessed the validity of the cytokine-induced hyperglycemia hypothesis by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with Covid-19 infection. METHOD(S) We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for Covid-19 infection. The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected. Hyperglycemia was defined as glucose levels >=140mg/dL. CRP >=100mg/L, ferritin >=530ng/ mL, LDH>=590U/L, and D-dimer >=0.5mg/L were considered elevated. We used Chi-square test for categorical variables, Mann Whitney U test for continuous variables, and calculated the logistic regression for hyperglycemia. RESULT(S) Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between the two groups. There were no statistically significant differences between serum inflammatory markers except LDH in patients with or without new-onset hyperglycemia [CRP(58.1%vs.65.6%,p-0.29), ferritin (48.4%vs.34.9%, p-0.14),D-dimer (37.1%vs.37.1%,p-0.76) & LDH (19.4%vs11.8%,p-0.02)]. However, Logistic regression analysis showed no difference in LDH levels between the two groups (OR-1.623,p-0.256). Additional analysis showed significantly higher mortality (24.2%vs.9.1%,p-0.001;OR-2.528,p-0.024) and length of stay(8.89 vs 6.69,p-0.026) in patients with hyperglycemia. CONCLUSION(S) Our pilot study showed no association between inflammatory marker levels and new-onset hyperglycemia in non-diabetic patients with Covid-19 infection, thus questioning the validity of the Covid-19 cytokine storm-induced stress hyperglycemia hypothesis. Our study also showed that new-onset hyperglycemia is an independent risk factor for higher mortality and length of stay. In light of the findings of our small single-center study, it becomes imperative to undertake a larger prospective study to understand the mechanism of SARS-CoV-2 infectioninduced hyperglycemia.