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

Alexi Vasbinder, Elizabeth Anderson, Husam Shadid, Hanna Berlin, Michael Pan, Tariq U Azam, Ibrahim Khaleel, Kishan Padalia, Chelsea Meloche, Patrick O'Hayer, Erinleigh Michaud, Tonimarie Catalan, Rafey Feroze, Pennelope Blakely, Christopher Launius, Yiyuan Huang, Lili Zhao, Lynn Ang, Monica Mikhael, Kara Mizokami-StoutSubramaniam Pennathur, Matthias Kretzler, Sven H Loosen, Athanasios Chalkias, Frank Tacke, Evangelos J Giamarellos-Bourboulis, Jochen Reiser, Jesper Eugen-Olsen (Member of study group), Eva L Feldman, Rodica Pop-Busui, Salim S Hayek, Salim S Hayek, Pennelope Blakely, Hanna Berlin, Tariq U Azam, Husam Shadid, Michael Pan, Patrick O'Hayer, Izzet Altintas (Member of study group), Marius Stauning (Member of study group), Morten Baltzer Houlind (Member of study group), Mette B Lindstrøm (Member of study group), Hejdi Gamst-Jensen (Member of study group), Line Jee Hartmann Rasmussen (Member of study group), Jan O Nehlin (Member of study group), Thomas Kallemose (Member of study group), Christian Rasmussen (Member of study group), Ove Andersen (Member of study group), Jens Tingleff (Member of study group), ISIC Study Group:

34 Citations (Scopus)


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.

Original languageEnglish
Article numberdc212102
JournalDiabetes Care
Issue number3
Pages (from-to)692-700
Number of pages9
Publication statusPublished - 1 Mar 2022


  • Biomarkers
  • COVID-19
  • Diabetes Mellitus/epidemiology
  • Female
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Hyperglycemia
  • Inflammation
  • Male
  • Middle Aged
  • SARS-CoV-2


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