@article{3202708,
    title = "Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.",
    author = "Vasbinder, Alexi and Anderson, Elizabeth and Shadid, Husam and Berlin, Hanna and Pan, Michael and Azam, Tariq U. and Khaleel, Ibrahim and Padalia, Kishan and Meloche, Chelsea and O'Hayer, Patrick and Michaud, Erinleigh and Catalan, Tonimarie and Feroze, Rafey and Blakely, Pennelope and Launius, Christopher and Huang, Yiyuan and Zhao, Lili and Ang, Lynn and Mikhael, Monica and Mizokami-Stout, Kara and Pennathur, Subramaniam and Kretzler, Matthias and Loosen, Sven H. and Chalkias, Athanasios and Tacke, Frank and Giamarellos-Bourboulis, Evangelos J. and Reiser, Jochen and Eugen-Olsen, Jesper and Feldman, Eva L. and Pop-Busui, Rodica and Hayek, Salim S. and Hayek, Salim S. and Blakely, Pennelope and Berlin, Hanna and Azam, Tariq U. and Shadid, Husam and Pan, Michael and O'Hayer, Patrick and Meloche, Chelsea and Feroze, Rafey and Padalia, Kishan J. and Anderson, Elizabeth and Perry, Danny and Bitar, Abbas and Kaakati, Rayan and Huang, Yiyuan and Zhao, Lili and Reiser, Jochen and Samelko, Beata and Hlepas, Alex and Patel, Priya P. and Wang, Xuexiang and Eugen-Olsen, Jesper and Altintas, Izzet and Stauning, Marius and Baltzer Houlind, Morten and Lindstrøm, Mette B. and Gamst-Jensen, Hejdi and Hartmann, Line Jee and Nehlin, Jan O. and Kallemose, Thomas and Parvaiz, Imran and Rasmussen, Christian and Andersen, Ove and Tingleff, Jens and Giamarellos-Bourboulis, Evangelos J. and Adami, Maria-Evangelia and Solomonidi, Nicky and Tsilika, Maria and Saridaki, Maria and Lekakis, Vasileios and Loosen, Sven H. and Luedde, Tom and Keitel, Verena and Chalkias, Athanasios and Arnaoutoglou, Eleni and Pantazopoulos, Ioannis and Laou, Eleni and Kolonia, Konstantina and Skoulakis, Anargyros and Tacke, Frank and Tober-Lau, Pinkus and Mohr, Raphael and Kurth, Florian and Sander, Leif Erik and Jochum, Christoph",
    journal = "DIABETES CARE",
    year = "2022",
    volume = "45",
    number = "3",
    pages = "692--700",
    issn = "0149-5992",
    doi = "10.2337/dc21-2102",
    keywords = "Humans, *COVID-19, SARS-CoV-2, Female, Male, Biomarkers, Middle Aged, Hospital Mortality, Inflammation, Hospitalization, *Diabetes Mellitus/epidemiology, *Hyperglycemia",
    abstract = "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."
}