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.