A new meta-analysis published on the preprint server medRxiv* by the researchers from the United States and Greece reveals that the likelihood of death is 65% higher in hospitalized coronavirus disease (COVID-19) patients with diabetes when compared to non-diabetics – urging the adequate glucose control in the era of the pandemic.
The current pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than six million people across the globe as of June 2020, amounting to 371 thousand deaths.
Diabetes mellitus is a serious condition that occurs when the glucose levels in the blood are overly high. Alongside a myriad of adverse consequences, diabetes is also associated with higher susceptibility to infectious diseases, but also higher infection-related mortality.
It is also known that diabetics have 40% higher rates of acquiring lower respiratory infections. During the swine flu pandemic, it was observed that diabetes basically tripled the risk of patient hospitalization and quadrupled the risk of their admission to the intensive care unit.
Some possible explanations of increased infection susceptibility are enhanced virulence of certain microorganisms in a high-glucose milieu, increased adherence of microorganisms in diabetic cells, as well as generally impaired immune response. These are the most significant factors that may potentially worsen COVID-19 outcomes in diabetic patients.
A research group from the Montefiore Medical Center, Albert Einstein College of Medicine and Jacobi Medical Center in the Bronx, NY (USA), as well as from the University of Piraeus in Attica, Greece, decided to conduct a meta-analysis of studies reporting on the link between diabetes and mortality in adult hospitalized individuals with COVID-19.
Study: Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients. Image Credit: Syda Productions / Shutterstock
An in-depth exploration of the medical literature
A systematic literature review approach by this research group entailed several relevant research databases (Google Scholar, MEDLINE, Embase, medRxiv). The observational studies demonstrating any type of association between diabetes and mortality of hospitalized COVID-19 patients were sought (up to May 10, 2020).
The analysis was guided in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model by DerSimonian and Laird was used, which is led by an assumption that different studies are evaluating different, yet correlated, intervention effects.
Moreover, a meta-regression analysis was carried out for important covariates to address high heterogeneity among studies that were included in the paper. In short, this was done to examine effect sizes and potential publication biases in further detail.
"Given the heterogeneity of the results across the literature, our meta-analysis comes to answer this significant question by utilizing a total sample of 18,506 patients", explain study authors led by Dr. Leonidas Palaiodimos from the Montefiore Medical Center and Albert Einstein College of Medicine in the Bronx.
Diabetes and COVID-19 mortality
The findings of this meta-analysis are consistent with the results obtained in large observational cohorts. The overall mortality was 65% higher in diabetic in-patients when compared to non-diabetic ones; however, significant heterogeneity of included studies has to be emphasized.
This striking association remained significant even when the analysis concentrated on geographical regions of study origin with (once again) significant heterogeneity. Still, the results have to be interpreted with caution.
"The main limitation of our study is the lack of data on glucose control prior or during hospitalization," caution study authors. This means that the exact association of controlled and uncontrolled diabetes with in-hospital mortality could not be estimated with enough granularity.
Finally, the conducted meta-regression analysis did not reveal any significant association with the frequency of other significant comorbidities across different publications and the results obtained by this study.
Implications for clinical practice
Diabetes is definitely one of the leading global causes of morbidity and death; hence, further studies are needed to assess whether the association between diabetes and COVID-19 mortality in hospitalized patients is independent or not, as well as to gauge the purported beneficial role of glucose control before or during the disease.
"In the meantime, attention should be paid in preventing diabetes and its complications and protecting this population from COVID-19 given a higher chance for adverse outcomes once they are diagnosed with the disease", say study authors in their paper.
This means that all diabetic patients with COVID-19 should be treated with special attention, given the possible higher risk for adverse outcomes in this subgroup. Many observational cohort studies around the world highlighted this notion.
And while the researchers recognize certain limitations of this study, they hope that their contribution will support the continuous investigation of the effect of SARS-CoV-2 infection in diabetic patients.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Palaiodimos, L. et al. (2020). Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients. medRxiv. https://doi.org/10.1101/2020.05.26.20113811.