Microvascular disease in diabetes and severe COVID-19 outcomes – Authors' reply
Authors: Helen M Colhoun, Stuart J McGurnaghan, Paul M McKeigue
Journal: The Lancet Diabetes & Endocrinology (2021)

We thank Antonella Corcillo and colleagues for their interest in our Article.1McGurnaghan SJ Weir A Bishop J et al.Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.Lancet Diabetes Endocrinol. 2021; 9: 82-93Summary Full Text Full Text PDF Scopus (233) Google Scholar We fully agree with them on the importance of the association between microvascular disease and severe COVID-19 and its manifestation as associations with reduced estimated glomerular filtration rate (eGFR), albuminuria, and retinopathy. We also agree that the role of endothelial dysfunction in microvascular disease in diabetes suggests a common mechanism for the association with severe COVID-19. Indeed, in preliminary drafts from our Article we discussed this point, but space requirements meant that it was not included in the final version. Indeed, there is increasing recognition of the involvement of endothelial damage and microvascular dysfunction in COVID-19.2Teuwen L-A Geldhof V Pasut A Carmeliet P COVID-19: the vasculature unleashed.Nat Rev Immunol. 2020; 20: 389-391Crossref PubMed Scopus (767) Google Scholar Endothelial dysfunction and microvascular disease are common in diabetes.3Chan NN Vallance P Colhoun HM Endothelium-dependent and -independent vascular dysfunction in type 1 diabetes: role of conventional risk factors, sex, and glycemic control.Arterioscler Thromb Vasc Biol. 2003; 23: 1048-1054Crossref PubMed Scopus (57) Google Scholar Albuminuria, reduced renal function, and retinopathy are all manifestations of endothelial damage and microvascular disease and all were associated with severe COVID-19 in our study. Regarding whether more advanced stages of chronic kidney disease were associated with worse COVID-19 outcomes, as observed in several studies,4Holman N Knighton P Kar P et al.Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.Lancet Diabetes Endocrinol. 2020; 8: 823-833Summary Full Text Full Text PDF PubMed Scopus (631) Google Scholar we note that this association is reported in Supplementary Table 6 of the appendix of our Article where we show that an eGFR of less than 30 mL/min per 1·73 m2 or being on renal replacement therapy was associated with a 2·37 times increased risk of severe COVID-19.1McGurnaghan SJ Weir A Bishop J et al.Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.Lancet Diabetes Endocrinol. 2021; 9: 82-93Summary Full Text Full Text PDF Scopus (233) Google Scholar As Corcillo and colleagues note, albuminuria was not selected in the prediction model. Missing values were imputed but, as Corcillo and colleagues also point out, collinearity with other variables can mean that strongly associated variables do not get selected. Because of the very strong association between albuminuria and reduced eGFR, and because eGFR was selected, the fact that albuminuria was not is unsurprising. As we note in our Article, "The variables retained in the model are those that are the most predictive and not necessarily causal".1McGurnaghan SJ Weir A Bishop J et al.Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.Lancet Diabetes Endocrinol. 2021; 9: 82-93Summary Full Text Full Text PDF Scopus (233) Google Scholar HMC reports grants and personal fees from Eli Lilly and Novo Nordisk; grants from AstraZeneca, Regeneron, and Pfizer; institutional fees from Novartis and Sanofi Aventis; and being a shareholder with Roche Pharmaceuticals. All other authors declare no competing interests. Microvascular disease in diabetes and severe COVID-19 outcomesRisks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland