Published online Feb 26, 2023. doi: 10.12998/wjcc.v11.i6.1287
Peer-review started: October 30, 2022
First decision: November 27, 2022
Revised: December 17, 2022
Accepted: February 3, 2023
Article in press: February 3, 2023
Published online: February 26, 2023
Processing time: 117 Days and 3.4 Hours
New onset hyperglycemia is common in patients with severe coronavirus disease 2019 (COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pancreatic β-cell failure have also been postulated to play a role.
We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia, particularly the rationale 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.
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 ≥ 140 mg/dL. C-Reactive protein (CRP) ≥ 100 mg/L, ferritin ≥ 530 ng/mL, lactate dehydrogenase (LDH) ≥ 590 U/L, and D-dimer ≥ 0.5 mg/L were considered elevated. We used the χ2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia.
Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic. Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows: 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) and LDH (19.4% vs 11.8%, P = 0.02). Logistic regression analysis showed LDH odds ratio (OR) = 1.623 (P = 0.256). We observed 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.
Our study showed no association between CRP, ferritin, LDH, D-dimer levels, and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection. It also shows an increased mortality risk and length of stay in patients with hyperglycemia. With new-onset hyperglycemia being closely associated with poor prognostic indices, it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia. We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding. This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.
Core Tip: Our study suggests that there is no correlation between the inflammatory marker levels and the presence of hyperglycemia in non-diabetic patients with coronavirus disease 2019 (COVID-19) infection. With an increased need to understand the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-induced hyperglycemia, we assessed the validity of the most accepted COVID-19 infection-induced cytokine storm-related stress hyperglycemia theory. However, our study did not show any correlation between inflammatory marker levels that correlate with the cytokine storm and the level of hyperglycemia. This suggests the possibility of other mechanisms playing a role in the SARS-CoV-2 infection-induced hyperglycemia. Our study also demonstrated that new-onset hyperglycemia was an independent risk factor for higher mortality and length of stay, thereby emphasizing the need to understand the mechanisms leading to hyperglycemia.