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

Abstract

Aims: 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 North-East 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 newly-diagnosed. 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 newly-diagnosed 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.

Keywords: Mediation; Metabolism; Observational; Prediction; SARS-CoV-2; Survival.

Fig. 1

Forest plots of the association of diabetes/hyperglycemia on COVID-19 outcomes. Unadjusted (A) and age- and sex-adjusted (B) analysis of the association between diabetes, as compared to no diabetes, split known diabetes versus newly-diagnosed diabetes and hyperglycemia (for each 2 mmol/l increase) with severe COVID-19. The primary severity outcome was admittance to the intensive care unit, or need of mechanical ventilation, or death (results of model 2 are detailed in Table 3, and not are graphically represented here since results were very similar to model 1).

Fig. 2

Correlation between admittance glucose levels and severity clinical variables. Clinical variables of COVID-19 severity are divided into those related to hemodynamics, respiratory, inflammatory, hematologic and tissue damage biomarkers. For each correlation plot, we show individual data points, the regression line with shadowed 95% C.I. between dashed lines, as well as the Pearson’s r correlation coefficient. *p < 0.05. When distribution of the dependent variable was highly skewed, the Y scale was log transformed.

Fig. 3

Mediators of the effects of hyperglycemia on COVID-19 outcomes. For each candidate mediator, the forest plot shows the association with the primary COVID-19 severity outcome (per each higher or lower SD), along with a histogram of their mediation effect on the association between glucose levels and COVID-19 severity. Mediation is expressed as percentage of the glucose effect on the primary outcome. Further details on the methods are given in the text, whereas full data are presented in Table S4.