TY - JOUR
TI - 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.
AU - Hayek, Salim S.
AU - Blakely, Pennelope
AU - Berlin, Hanna
AU - Azam, Tariq U.
AU - Shadid, Husam
AU - Pan, Michael
AU - O'Hayer, Patrick
AU - Meloche, Chelsea
AU - Feroze, Rafey
AU - Padalia, Kishan J.
AU - Anderson, Elizabeth
AU - Perry, Danny
AU - Bitar, Abbas
AU - Kaakati, Rayan
AU - Huang, Yiyuan
AU - Zhao, Lili
AU - Reiser, Jochen
AU - Samelko, Beata
AU - Hlepas, Alex
AU - Patel, Priya P.
AU - Wang, Xuexiang
AU - Eugen-Olsen, Jesper
AU - Altintas, Izzet
AU - Stauning, Marius
AU - Baltzer Houlind, Morten
AU - Lindstrøm, Mette B.
AU - Gamst-Jensen, Hejdi
AU - Hartmann, Line Jee
AU - Nehlin, Jan O.
AU - Kallemose, Thomas
AU - Parvaiz, Imran
AU - Rasmussen, Christian
AU - Andersen, Ove
AU - Tingleff, Jens
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Adami, Maria-Evangelia
AU - Solomonidi, Nicky
AU - Tsilika, Maria
AU - Saridaki, Maria
AU - Lekakis, Vasileios
AU - Loosen, Sven H.
AU - Luedde, Tom
AU - Keitel, Verena
AU - Chalkias, Athanasios
AU - Arnaoutoglou, Eleni
AU - Pantazopoulos, Ioannis
AU - Laou, Eleni
AU - Kolonia, Konstantina
AU - Skoulakis, Anargyros
AU - Tacke, Frank
AU - Tober-Lau, Pinkus
AU - Mohr, Raphael
AU - Kurth, Florian
AU - Sander, Leif Erik
AU - Jochum, Christoph
JO - DIABETES CARE
PY - 2022
VL - 45
TODO - 3
SP - 692--700
PB - 
SN - 0149-5992
TODO - 10.2337/dc21-2102
TODO - Humans, *COVID-19, SARS-CoV-2, Female, Male, Biomarkers, Middle Aged, Hospital Mortality, Inflammation, Hospitalization, *Diabetes Mellitus/epidemiology, *Hyperglycemia
TODO - 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  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 than those  without DM. Among 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 hyperinflammation as assessed by suPAR levels, while  the impact of hyperglycemia is independent of inflammation.
ER -