To the Editor: We welcome the letters by Sardu et al [1] and Lepper et al [2] on our paper entitled ‘Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study’ [3]. Sardu et al found that the change in blood glucose concentration between admission and 24 h was associated with coronavirus disease-2019 (COVID-19) outcome in 132 Italian hyperglycaemic (i.e. blood glucose >7.7 mmol/l on admission) patients hospitalised for both severe and non-severe disease [1]. In addition, Lepper et al reported data on an impressive cohort of nearly 7000 patients with community-acquired pneumonia (CAP) and demonstrated that elevated blood glucose on admission was associated with an increased risk of death in individuals with or without pre-existing diabetes [2, 4]. Both studies emphasised the value of admission blood glucose on prognosis of COVID-19 and of CAP [2].
Sardu et al considered that we misinterpreted our data on admission blood glucose, since we claimed that we considered it to be a consequence of, rather than a contributor to COVID-19 severity. This point is of scientific and medical interest. They acknowledged a prognostic role for admission blood glucose, which is in line with our findings, and, furthermore, suggested that hyperglycaemia is more than a simple marker of the severity of the infection. We believe that their interesting results should not lead to any alteration of our conclusion on the value of admission blood glucose for several reasons. First, the study by Sardu et al was purely observational and so causation cannot be established: the greater decrease in blood glucose between those with a better outcome compared with the others does not imply that this improvement is causal. Second, Van den Berghe et al could not find evidence of a benefit on all-cause death of strict blood glucose control with insulin compared with conventional therapy in a study of 1200 patients admitted to the medical ICU, with half of the participants having respiratory conditions [5].
We fully agree with Lepper et al that admission blood glucose can be used as a stratification factor to identify patients at high risk of severe pneumonia [2, 4]. However, based on our results from the Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study [3], other biomarkers, such as C-reactive protein, lymphocyte counts or aspartate aminotransferase, which outperformed blood glucose in multivariable analysis, could have adequate power for such a stratification and should not be forgotten.
In conclusion, whether blood glucose in COVID-19 is a causal factor requiring specific treatment or a mere marker remains to be established in future dedicated studies including randomised controlled trials.
Abbreviations
- CAP:
-
Community-acquired pneumonia
- COVID-19:
-
Coronavirus disease-2019
References
Sardu C, D’Onofrio N, Balestrieri ML et al (2020) Hyperglycaemia on admission to hospital and COVID-19. Diabetologia. https://doi.org/10.1007/s00125-020-05216-2
Lepper PM, Bals R, Jüni P, von Eynatten M (2020) Blood glucose, diabetes and metabolic control in patients with community-acquired pneumonia. Diabetologia. https://doi.org/10.1007/s00125-020-05225-1
Cariou B, Hadjadj S, Wargny M et al (2020) Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia 63:1500–1515. https://doi.org/10.1007/s00125-020-05180-x
Lepper PM, Ott S, Nüesch E et al (2012) Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 344:e3397. https://doi.org/10.1136/bmj.e3397
Van den Berghe G, Wilmer A, Hermans G et al (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461. https://doi.org/10.1056/NEJMoa052521
Acknowledgements
We thank sponsor (DRCI [délégation à la recherche clinique et à l’innovation]) CHU Nantes. We also thank the CORONADO Study staff at CHU Nantes, Nantes, France: Clinical Project Manager (M. Saignes) and assistant (J. Saunier), Clinical Research Associates (S. El Andaloussi, J. Martin-Gauthier, E. Rebouilleau) and data managers (B. Guyomarch, T. Roman). We acknowledge all medical staff involved in the diagnosis and treatment of patients with COVID-19 in CORONADO participating centres. We thank the Société Francophone du Diabète (SFD) and Société Française d’Endocrinologie (SFE) for disseminating study design and organisation and the Fédération Française des Diabétiques (FFD) for participating in the study organisation.
Authors’ relationships and activities
BC reports grants and personal fees from Amgen, personal fees from AstraZeneca, personal fees from Akcea, personal fees from Genfit, personal fees from Gilead, personal fees from Eli Lilly, personal fees from Novo Nordisk, personal fees from MSD, grants and personal fees from Sanofi, and grants and personal fees from Regeneron. SH reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Bayer, personal fees from Boehringer Ingelheim, grants from Dinno Santé, personal fees from Eli Lilly, non-financial support from LVL, personal fees and non-financial support from MSD, personal fees from Novartis, personal fees and non-financial support from Novo Nordisk, grants from Pierre Fabre Santé, personal fees and non-financial support from Sanofi, personal fees and non-financial support from Servier, and personal fees from Valbiotis. MW reports personal fees from Novo Nordisk. MP reports personal fees and non-financial support from Novo Nordisk, non-financial support from Sanofi, and non-financial support from Amgen. SB reports personal fees from Novo Nordisk, personal fees from Sanofi, personal fees from Eli Lilly, personal fees from Medtronic, and personal fees from Abbott. PD reports personal fees from Novo Nordisk, personal fees from Sanofi, personal fees from Eli Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Abbott, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, and personal fees from Mundipharma. BG reports personal fees from Eli Lilly, personal fees from Novo Nordisk, personal fees from Mellitus Care, personal fees from Isis Diabetes, and grants from Boehringer Ingelheim. MJ reports personal fees and non-financial support from Sanofi, personal fees and non-financial support from Eli Lilly, personal fees and non-financial support from Novo Nordisk, grants and personal fees from Boehringer Ingelheim, grants, personal fees and non-financial support from Medtronic, personal fees and non-financial support from Abbott, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, and grants, personal fees and non-financial support from AstraZeneca. LP reports personal fees and non-financial support from Sanofi, personal fees and non-financial support from Eli Lilly, personal fees and non-financial support from Novo Nordisk, and personal fees and non-financial support from MSD. RR reports grants, personal fees and non-financial support from Sanofi, grants, personal fees and non-financial support from Novo Nordisk, personal fees and non-financial support from Eli Lilly, personal fees from Mundipharma, personal fees from Janssen, personal fees from Servier, grants and personal fees from AstraZeneca, personal fees from MSD, personal fees from Medtronic, personal fees from Abbott, grants from Diabnext, and personal fees from Applied Therapeutics. JFG reports personal fees and non-financial support from Eli Lilly, personal fees and non-financial support from Novo Nordisk, personal fees and non-financial support from Gilead, and personal fees and non-financial support from AstraZeneca. PG reports personal fees from Abbott, personal fees from Amgen, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from MSD, personal fees from Mundipharma, grants and personal fees from Novo Nordisk, personal fees from Sanofi, and personal fees from Servier. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Funding
The CORONADO study received funding from: the Fondation Francophone de Recherche sur le Diabète (FFRD), supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly and FFD (Fédération Française des Diabétiques) – CORONADO initiative emergency grant; Société Francophone du Diabète (SFD) - CORONADO initiative emergency grant, and CHU Nantes (Fonds de Dotation- projet CORONADO). All research facilities are acknowledged for providing research associates and research technicians for clinical investigations pro bono. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The study sponsor/funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.
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BC, JFG, PG, SH, MP and MW were responsible for the concept and design. SH and BC drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version of the text. Fundraising for the CORONADO study was carried out by BC, PG, SH, MP and BB.
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Cariou, B., Hadjadj, S., Wargny, M. et al. Blood glucose levels and COVID-19. Reply to Sardu C, D’Onofrio N, Balestrieri ML et al [letter] and Lepper PM, Bals R, Jüni P et al [letter]. Diabetologia 63, 2491–2494 (2020). https://doi.org/10.1007/s00125-020-05255-9
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DOI: https://doi.org/10.1007/s00125-020-05255-9