TY - JOUR
T1 - Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19
AU - Vasbinder, Alexi
AU - Anderson, Elizabeth
AU - Shadid, Husam
AU - Berlin, Hanna
AU - Pan, Michael
AU - Azam, Tariq U.
AU - Khaleel, Ibrahim
AU - Padalia, Kishan
AU - Meloche, Chelsea
AU - O’hayer, Patrick
AU - Michaud, Erinleigh
AU - Catalan, Tonimarie
AU - Feroze, Rafey
AU - Blakely, Pennelope
AU - Launius, Christopher
AU - Huang, Yiyuan
AU - Zhao, Lili
AU - Ang, Lynn
AU - Mikhael, Monica
AU - Mizokami-Stout, Kara
AU - Pennathur, Subramaniam
AU - Kretzler, Matthias
AU - Loosen, Sven H.
AU - Chalkias, Athanasios
AU - Tacke, Frank
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Reiser, Jochen
AU - Eugen-Olsen, Jesper
AU - Feldman, Eva L.
AU - Pop-Busui, Rodica
AU - Hayek, Salim S.
N1 - Publisher Copyright:
© 2022 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www. diabetesjournals.org/journals/pages/license.
PY - 2022/3
Y1 - 2022/3
N2 - 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 (ISIC), a multicen-ter 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-hospi-tal 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 than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plas-minogen 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 hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.
AB - 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 (ISIC), a multicen-ter 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-hospi-tal 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 than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plas-minogen 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 hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.
UR - http://www.scopus.com/inward/record.url?scp=85129353776&partnerID=8YFLogxK
U2 - 10.2337/dc21-2102
DO - 10.2337/dc21-2102
M3 - Article
AN - SCOPUS:85129353776
SN - 0149-5992
VL - 45
SP - 692
EP - 700
JO - Diabetes Care
JF - Diabetes Care
IS - 3
ER -