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Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19

Objective: Diabetes mellitus (DM) is a
major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons
that are unclear. 

Research Design and Methods: We leveraged The International
Study of Inflammation in COVID-19, a multicenter observational study of 2,044
patients hospitalized with COVID-19, to characterize the impact of DM on
in-hospital outcomes and assess the contribution of inflammation and
hyperglycemia to the risk attributed to DM. We measured biomarkers of
inflammation collected at hospital admission and collected glucose levels and
insulin data throughout hospitalization. The primary outcome was the
composite of in-hospital death, need for mechanical ventilation, and need for
renal replacement therapy.

Results: Among participants (mean age, 60 years; 58.2%
males), those with DM (n=686, 33.5%) had a significantly higher cumulative
incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of
inflammatory biomarkers compared to those without DM. Amongst biomarkers, DM
was only associated with higher soluble urokinase plasminogen activator
receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels
abrogated the association between DM and the primary outcome (adjusted
odds ratio 1.23[95%CI:0.78,1.37]). In mediation analysis, we estimated the
proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%.
Hyperglycemia and higher insulin doses were independent predictors of the primary
outcome, with effect sizes unaffected by adjusting for suPAR levels. 

Conclusions:
Our findings suggest that the association between DM and outcomes in COVID-19
is largely mediated by hyper-inflammation as assessed by suPAR levels, while the
impact of hyperglycemia is independent of inflammation.


