What causes worse outcomes?
The evidence for the increased adverse outcomes of COVID-19 due to pre-existing diabetes is consistent. For example, diabetes prevalence among COVID-19-deceased Italian cohort was 35.5% and only 20.3% in the general Italian citizens with the same age and gender distribution.4 One explanation is the fact that diabetes usually coexists with other cardiovascular disease especially hypertension which has been shown to be associated with worse outcomes in COVID-19.5-8Poorly controlled diabetes is also associated with increased oxidative stress and increased inflammatory cytokines such as tumour necrosis factor and interleukin-6, due to increased insulin resistance, which may increase the risk of progression to severe disease. 37 In addition, endothelial dysfunction and enhanced platelet aggregation lead to the development of a hypercoagulable, pro-thrombotic state that may contribute to poor control of the virus replication, prolonged pro-inflammatory response and eventually poor outcome. 22 Diabetes may also be associated with decreased forced expiratory volume and forced vital capacity compromising optimal pulmonary function. 48Diabetes -related complications may also be a factor. Microangiopathic changes that occur in the respiratory tract may impair gas exchange and lung compliance increasing susceptibility to lower respiratory tract infections by atypical microorganisms and severe pneumonias.37
Other mechanisms may be related to the fact that the COVID-19 virus gains entry to pulmonary cells through binding to the membrane ACE2 receptor. The ACE inhibitors, ARBs and non-steroidal anti-inflammatory drugs appear to increase ACE2 receptors expression and therefore their use in people with diabetes may increase COVID-19 infectivity and illness severity. 49 On the contrary to this, these medications may reduce the pulmonary and systemic inflammatory response by decreasing cytokines and therefore may be beneficial.50 Therefore, it is still unclear what is the balance between the benefits and the risks might be in continuing or stopping RAAS inhibitors. Other drugs used in the treatment of COVID-19 may have a deleterious effect on blood glucose level regulation such as the hyperglycaemic effect of glucocorticoids and the hypoglycaemic effect of hydroxychloroquine although this has not been clearly reported in the literature.