key: cord-0689527-qb1mvff7
authors: Colhoun, Helen M; McGurnaghan, Stuart J; McKeigue, Paul M
title: Microvascular disease in diabetes and severe COVID-19 outcomes – Authors' reply
date: 2021-03-16
journal: Lancet Diabetes Endocrinol
DOI: 10.1016/s2213-8587(21)00055-3
sha: 9fa9798c0a5a52692351608f05f7a7428ca80c32
doc_id: 689527
cord_uid: qb1mvff7

nan

www.thelancet.com/diabetes-endocrinology Vol 9 April 2021 201

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". 1 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. 

We thank Antonella Corcillo and colleagues for their interest in our Article. 1 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. 2 Endothelial dysfunction and microvascular disease are common in diabetes. 3 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, 4 we note that this association is reported in Supplementary Pre-existing pulmonary endothelial dysfunction and microangiopathy can affect gas exchange. 4 Homoeostasis, through capillary recruitment, will then no longer be achieved in severe COVID-19, contributing to the severity of adult respiratory distress syndrome in patients with COVID-19. 6 Retinopathy or albuminuria may represent a burden of pre-existing pulmonary microangiopathy. Further research is needed to assess the role of microvascular disease in diabetes and severe COVID-19 outcomes.

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

Diabetic retinopathy is independently associated with increased risk of intubation: a single centre cohort study of patients with diabetes hospitalised with COVID-19

The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19

Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study

Inflammation and intussusceptive angiogenesis in COVID-19: everything in and out of flow

We declare no competing interests.