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

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Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19. / Vasbinder, Alexi; Anderson, Elizabeth; Shadid, Husam; Berlin, Hanna; Pan, Michael; Azam, Tariq U; Khaleel, Ibrahim; Padalia, Kishan; Meloche, Chelsea; O'Hayer, Patrick; Michaud, Erinleigh; Catalan, Tonimarie; Feroze, Rafey; Blakely, Pennelope; Launius, Christopher; Huang, Yiyuan; Zhao, Lili; Ang, Lynn; Mikhael, Monica; Mizokami-Stout, Kara; Pennathur, Subramaniam; Kretzler, Matthias; Loosen, Sven H; Chalkias, Athanasios; Tacke, Frank; Giamarellos-Bourboulis, Evangelos J; Reiser, Jochen; Eugen-Olsen, Jesper; Feldman, Eva L; Pop-Busui, Rodica; Hayek, Salim S; ISIC Study Group.

In: DIABETES CARE, Vol. 45, No. 3, 01.03.2022, p. 692-700.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vasbinder, A, Anderson, E, Shadid, H, Berlin, H, Pan, M, Azam, TU, Khaleel, I, Padalia, K, Meloche, C, O'Hayer, P, Michaud, E, Catalan, T, Feroze, R, Blakely, P, Launius, C, Huang, Y, Zhao, L, Ang, L, Mikhael, M, Mizokami-Stout, K, Pennathur, S, Kretzler, M, Loosen, SH, Chalkias, A, Tacke, F, Giamarellos-Bourboulis, EJ, Reiser, J, Eugen-Olsen, J, Feldman, EL, Pop-Busui, R, Hayek, SS & ISIC Study Group 2022, 'Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19', DIABETES CARE, vol. 45, no. 3, pp. 692-700. https://doi.org/10.2337/dc21-2102

APA

Vasbinder, A., Anderson, E., Shadid, H., Berlin, H., Pan, M., Azam, T. U., Khaleel, I., Padalia, K., Meloche, C., O'Hayer, P., Michaud, E., Catalan, T., Feroze, R., Blakely, P., Launius, C., Huang, Y., Zhao, L., Ang, L., Mikhael, M., ... ISIC Study Group (2022). Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19. DIABETES CARE, 45(3), 692-700. https://doi.org/10.2337/dc21-2102

Vancouver

Vasbinder A, Anderson E, Shadid H, Berlin H, Pan M, Azam TU et al. Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19. DIABETES CARE. 2022 Mar 1;45(3):692-700. https://doi.org/10.2337/dc21-2102

Bibtex

@article{95cf8bdfa0ae41bcbc7c900a9a9272ff,
title = "Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19",
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.",
keywords = "Biomarkers, COVID-19, Diabetes Mellitus/epidemiology, Female, Hospital Mortality, Hospitalization, Humans, Hyperglycemia, Inflammation, Male, Middle Aged, SARS-CoV-2",
author = "Alexi Vasbinder and Elizabeth Anderson and Husam Shadid and Hanna Berlin and Michael Pan and Azam, {Tariq U} and Ibrahim Khaleel and Kishan Padalia and Chelsea Meloche and Patrick O'Hayer and Erinleigh Michaud and Tonimarie Catalan and Rafey Feroze and Pennelope Blakely and Christopher Launius and Yiyuan Huang and Lili Zhao and Lynn Ang and Monica Mikhael and Kara Mizokami-Stout and Subramaniam Pennathur and Matthias Kretzler and Loosen, {Sven H} and Athanasios Chalkias and Frank Tacke and Giamarellos-Bourboulis, {Evangelos J} and Jochen Reiser and Jesper Eugen-Olsen and Feldman, {Eva L} and Rodica Pop-Busui and Hayek, {Salim S} and {ISIC Study Group} and Hayek, {Salim S} and Pennelope Blakely and Hanna Berlin and Azam, {Tariq U} and Husam Shadid and Michael Pan and Patrick O'Hayer and Chelsea Meloche and Rafey Feroze and Padalia, {Kishan J} and Elizabeth Anderson and Danny Perry and Abbas Bitar and Rayan Kaakati and Yiyuan Huang and Lili Zhao and Jochen Reiser and Beata Samelko and Alex Hlepas and Patel, {Priya P} and Xuexiang Wang and Jesper Eugen-Olsen and Izzet Altintas and Marius Stauning and {Baltzer Houlind}, Morten and Lindstr{\o}m, {Mette B} and Hejdi Gamst-Jensen and Hartmann, {Line Jee} and Nehlin, {Jan O} and Thomas Kallemose and Imran Parvaiz and Christian Rasmussen and Ove Andersen and Jens Tingleff and Giamarellos-Bourboulis, {Evangelos J} and Maria-Evangelia Adami and Nicky Solomonidi and Maria Tsilika and Maria Saridaki and Vasileios Lekakis and Loosen, {Sven H} and Tom Luedde and Verena Keitel and Athanasios Chalkias and Eleni Arnaoutoglou and Ioannis Pantazopoulos and Eleni Laou and Konstantina Kolonia and Anargyros Skoulakis and Frank Tacke and Pinkus Tober-Lau and Raphael Mohr and Florian Kurth and Sander, {Leif Erik} and Christoph Jochum",
note = "{\textcopyright} 2022 by the American Diabetes Association.",
year = "2022",
month = mar,
day = "1",
doi = "10.2337/dc21-2102",
language = "English",
volume = "45",
pages = "692--700",
journal = "DIABETES CARE",
issn = "0149-5992",
publisher = "American Diabetes Association Inc.",
number = "3",

}

RIS

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

AU - ISIC Study Group

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

N1 - © 2022 by the American Diabetes Association.

PY - 2022/3/1

Y1 - 2022/3/1

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 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.

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 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.

KW - Biomarkers

KW - COVID-19

KW - Diabetes Mellitus/epidemiology

KW - Female

KW - Hospital Mortality

KW - Hospitalization

KW - Humans

KW - Hyperglycemia

KW - Inflammation

KW - Male

KW - Middle Aged

KW - SARS-CoV-2

U2 - 10.2337/dc21-2102

DO - 10.2337/dc21-2102

M3 - SCORING: Journal article

C2 - 35045184

VL - 45

SP - 692

EP - 700

JO - DIABETES CARE

JF - DIABETES CARE

SN - 0149-5992

IS - 3

ER -