Diabetes worsens COVID-19 prognosis

Previous research has shown that both type 1 and type 2 diabetes are associated with increased morbidity and mortality from COVID-19 infection. However, we don’t know if this increased risk arises from diabetes itself or its associated comorbidities, such as obesity and heart disease – or whether both are important. A new analysis, reported in a recent issue of Diabetologia, from the French CORONADO study of people hospitalised for COVID-19, shows that diabetes is an independent risk factor for a worse prognosis. Dr Susan Aldridge reports.

Early on in the COVID-19 pandemic, diabetes was found to be associated with an increased risk of severe outcomes, including death. Several studies subsequently confirmed this, including a whole-population analysis from England, showing an increase of COVID-19 related mortality, and a greater risk of COVID-19- related death or intensive care unit admission in Scotland – both studies comparing people with and without diabetes. But it’s not known whether this increased risk relates to diabetes itself, or to its comorbidities – or maybe both.

While there have been studies looking at the impact of single comorbidities, none has looked at how the burden of multimorbidity might affect COVID-19 outcomes in diabetes. However, there has been a review of observational studies that suggests that those whom the authors define as having a ‘more severe course’ of diabetes, and therefore more comorbidities, have a poorer COVID-19 prognosis compared with those who have ‘a milder course’ of diabetes.

To address the need to clarify the relationship between diabetes, multimorbidity and COVID-19 outcomes, the CORONADO team in France has carried out a dedicated study.

The CORONADO study

The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study is a French nationwide study, with both retrospective and prospective data collection, looking at the phenotypic characteristics and prognosis of people with diabetes admitted to hospital with COVID-19 between 10 March and 10 April 2020. As such, it was well set up for carrying out this new study, whose objective was to determine whether diabetes is a prognostic factor for COVID-19, independent of age and diabetes-associated comorbidities. The diabetes cohort was matched 1:1 for age, sex and date of admission to hospital with participants who did not have diabetes. The researchers then compiled a measure known as the Charleson comorbidity index (CCi) for each participant, from their medical records. The CCi is used to capture comorbidities associated with mortality risk and, for the purposes of the study analysis, two versions were used – with diabetes either included or excluded as a comorbidity. The primary composite outcome set for the study was invasive mechanical ventilation (IMV) and/or death within 7 days or 28 days.

Diabetes and COVID-19 outcomes

There were 2210 people with diabetes matched with 2210 people without the condition in this study. Most had type 2 diabetes and, compared with the matched individuals, they were more likely to have obesity, hypertension, dyslipidaemia and/or cardiovascular disease, as you’d expect, and so their CCi, with and without diabetes included, was higher. And, on admission, the individuals with diabetes had higher blood glucose levels and lower estimated glomerular filtration rates (eGFRs).

Invasive mechanical ventilation and/or death within seven days occurred in 29.0% of the diabetes group compared with 21.6% of those without diabetes, and in 34.8% and 28.4%, respectively, within 28 days. Each individual outcome – IMV and death – occurred more frequently in those with diabetes.

A statistical analysis of the data showed that diabetes is independently associated with worse COVID-19 prognosis irrespective of comorbidity burden in a population hospitalised for the infection in France during the first wave of the pandemic. These findings add to other research showing that diabetes confers susceptibility to infectious disease, particularly influenza and pneumonia. Such susceptibility was also reported during the 2009 H1N1 influenza pandemic and in the more recent MERS-CoV outbreak.

Explaining the impact of diabetes on morbidity and mortality from COVID-19 is beyond the scope of this paper, but is urgently in need of further investigation. It’s been suggested that hyperglycaemia might play a role. The nationwide survey report from Scotland did find an association between HbA1c and COVID-19 severity, but the authors didn’t find that in the current study. And the study of the UK population found an increased risk of COVID-19 death in people with diabetes irrespective of their HbA1c level. However, the current study did notice a link between higher plasma glucose at admission and COVID-19 severity. The higher glucose could merely be a result of infection, or it may interfere with the immune response, worsening the outcome.

The authors note that their study was carried out during the first wave of the pandemic. Prevention and treatment of COVID-19 have improved since then. Further studies are needed to see if this has also improved outcomes, specifically for those with diabetes. Also, the population studied was severely ill, so we don’t know if the worse outcomes for those with diabetes would also be observed in the general population.

Unfortunately, as we know, COVID-19 has not gone away. As healthcare systems gear up to deal with further waves of infection during the autumn and winter months, these findings should be used to plan and target specific interventions to reduce COVID-19 morbidity and mortality among those with diabetes.

To read this paper, go to: Cariou B, Wargny M, Boureau A-S, Smati S, Tramunt B, Desailloud R, Lebeault M, Amadou C, Ancelle D, Belkau B, Bordier L, Borot S, Bourgeon M, Bourron O, Cosson E, Eisinger M, Gonfroy-Leymarie C, Julia J-B, Marchand L, Meyer L, Seret-Begeue D, Simon D, Sultan A, Thivolet C, Vambergue A, Vatier C, Winiszewski P, Saulner P-J, Bauduceau B, Gourdy P, Hadjadj S and on behalf of the CORONADO investigators. Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative. Diabetologia online 15 June 2022. https://doi.org/10.1007/s00125-022-05734-1

For more on the CORONADO initiative, watch Professor Samy Jadjadj’s contribution to our series Diabetes and COVID-19, Answering questions of risk.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.