Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study
Authors: Mayerhöfer Timo , Klein Sebastian , Wernly Bernhard , Flaatten Hans , Guidet Bertrand , De Lange Dylan W. , Fjølner Jesper , Leaver Susannah , Beil Michael , Sviri Sigal , Bruno Raphael Romano , Artigas Antonio , van Heerden Peter Vernon , Pinto Bernardo Bollen , Schefold Joerg C. , Moreno Rui , Cecconi Maurizio , Szczeklik Wojciech , Jung Christian , Joannidis Michael ,   COVIP study group, Eller Philipp , Mesotten Dieter , Reper Pascal , Oeyen Sandra , Swinnen Walter , Brix Helene , Brushoej Jens , Villefrance Maja , Nedergaard Helene Korvenius , Bjerregaard Anders Thais , Balleby Ida Riise , Andersen Kasper , Hansen Maria Aagaard , Uhrenholt Stine , Bundgaard Helle , Mohamed Aliae A. R. Hussein , Salah Rehab , Ali Yasmin Khairy NasrEldin Mohamed , Wassim Kyrillos , Elgazzar Yumna A , Tharwat Samar , Azzam Ahmed Y. , Habib Ayman abdelmawgoad , Abosheaishaa Hazem Maarouf , Azab Mohammed A , Galbois Arnaud , Charron Cyril , Guerot Emmanuel , Besch Guillaume , Rigaud Jean-Philippe , Maizel Julien , Djibré Michel , Burtin Philippe , Garcon Pierre , Nseir Saad , Valette Xavier , Alexandru Nica , Marin Nathalie , Vaissiere Marie , Plantefeve Gaëtan , Vanderlinden Thierry , Jurcisin Igor , Megarbane Buno , Caillard Anais , Valent Arnaud , Garnier Marc , Besset Sebastien , Oziel Johanna , Raphaelen Jean-herlé , Dauger Stéphane , Dumas Guillaume , Goncalves Bruno , Piton Gaël , Kelm Malte , Wolff Georg , Barth Eberhard , Goebel Ulrich , Barth Eberhard , Kunstein Anselm , Schuster Michael , Welte Martin , Lutz Matthias , Meybohm Patrick , Steiner Stephan , Poerner Tudor , Haake Hendrik , Schaller Stefan , Kindgen-Milles Detlef , Meyer Christian , Kurt Muhammed , Kuhn Karl Friedrich , Randerath Winfried , Wollborn Jakob , Dindane Zouhir , Kabitz Hans-Joachim , Voigt Ingo , Shala Gonxhe , Faltlhauser Andreas , Rovina Nikoletta , Aidoni Zoi , Chrisanthopoulou Evangelia , Papadogoulas Antonios , Gurjar Mohan , Mahmoodpoor Ata , Ahmed Abdullah khudhur , Marsh Brian , Elsaka Ahmed , Comellini Vittoria , Rabha Ahmed , Ahmed Hazem , a Namendys-Silva Silvio , Ghannam Abdelilah , Groenendijk Martijn , Zegers Marieke , de Lange Dylan , Cornet Alex , Evers Mirjam , Haas Lenneke , Dormans Tom , Dieperink Willem , Romundstad Luis , Sjøbø Britt , Andersen Finn H , Strietzel Hans Frank , Olasveengen Theresa , Hahn Michael , Czuczwar Miroslaw , Gawda Ryszard , Klimkiewicz Jakub , de Lurdes Campos Santos Maria , Gordinho André , Santos Henrique , Assis Rui , Oliveira Ana Isabel Pinho , Badawy Mohamed Raafat , Perez-Torres David , Gomà Gemma , Villamayor Mercedes Ibarz , Mira Angela Prado , Cubero Patricia Jimeno , Rivera Susana Arias , Tomasa Teresa , Iglesias David , Vázquez Eric Mayor , Aldecoa Cesar , Ferreira Aida Fernández , Zalba-Etayo Begoña , Canas-Perez Isabel , Tamayo-Lomas Luis , Diaz-Rodriguez Cristina , Sancho Susana , Priego Jesús , Abualqumboz Enas M.Y. , Hilles Momin Majed Yousuf , Saleh Mahmoud , Ben-HAmouda Nawfel , Roberti Andrea , Dullenkopf Alexander , Fleury Yvan , Schefold Joerg C , Al-Sadawi Mohammed , Serck Nicolas , Dewaele Elisabeth , Kumar Pritpal , Bundesen Camilla , Innes Richard , Gooch James , Cagova Lenka , Potter Elizabeth , Reay Michael , Davey Miriam , Humphreys Sally , Berlemont Caroline Hauw , Chousterman Benjamin Glenn , Dépret François , Ferre Alexis , Vettoretti Lucie , Thevenin Didier , Faltlhauser Andreas , Milovanovic Milena , Simon Philipp , Lorenz Marco , Stoll Sandra Emily , Dubler Simon , Fuest Kristina , Mulita Francesk , Kondili Eumorifa , Andrianopoulos Ioannis , Meynaar Iwan , Cornet Alexander Daniel , Sjøbøe Britt , Kluzik Anna , Zatorski Paweł , Drygalski Tomasz , Solek-pastuszka Joanna , Onichimowski Dariusz , Stefaniak Jan , Stefanska-Wronka Karina , Zabul Ewa , Cardoso Filipe Sousa , Banzo Maria José Arche , Tomasa-Irriguible Teresa Maria , Mira Ángela Prado , Arias-Rivera Susana , Frutos-Vivar Fernando , Lopez-Cuenca Sonia , de Gopegui Pablo Ruiz , Abidi Nour , Chau Ivan , Pugh Richard , Smuts Sara , Zotter Klemens 
Published: March 2023

Abstract
Background
Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age.

Methods
This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan–Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality.

Results
This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06–1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis.

Conclusion
Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19.

Study registration
NCT04321265, registered March 19th, 2020.