Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

Diabetes could be a risk factor for severity in patients with Covid-19. Acute respiratory distress syndrome and Disseminated Intravascular Coagulation usually occur in the second week of the disease, concomitantly with cytokine storm and hypercoagulable state [1].

Diabetes could contribute to the loss of capacity to regulate immunity. The dysfunction of the autonomic nervous system might determine the pro-inflammatory state in diabetic Covid-19 patients, as a result of a dysregulation of the inflammatory reflex, where vagal afferent fibres, receiving sensory inputs from the immune cells, activate vagal efferent fibres, responsible for mitigating macrophage activation [2].

Furthermore, diabetes is associated with structural alterations in the lung, as the thickening of the pulmonary basal laminae and of the alveolar epithelium, concurrent with reduction of DLCO [3]. Other aspects are a higher prevalence of a restrictive spirometry pattern and a decreased respiratory muscle endurance [4]. These abnormalities might worsen conditions associated with increased pulmonary demands, such as respiratory infections [4]. In addition, Diabetic Autonomic Neuropathy could induce functional alterations in the regulation of bronchomotor tone and in the control of ventilation [3].

Finally, diabetes mellitus is considered a pro-thrombotic state in which hyperglycemia and inflammation directly contribute to abnormal platelet activation, higher concentration of fibrinogen and other coagulation factors [5]. Moreover generation of AGEs and ROS leads to an endothelial injury, with an increased levels and structural alterations in von Willebrand factor, that are associated with thrombotic angiopathies [6]. In Covid-19, which may be associated with both venous and arterial thromboembolic disease, due to inflammation, hypoxia, immobilization, and disseminated intravascular coagulation [7], diabetes could further contribute to hypercoagulable state.

Funding

The authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.