4.6 Hyperglycemia in COVID-19
Although there is no related epidemiological study about the diabetes in
COVID-19 patients, we speculate that the patients with diabetes may have
worse prognosis. A retrospective study published in LANCET found
that half of patients infected with COVID-19 were associated with
chronic diseases(Chen et al. , 2020), mainly including diabetes,
cardiovascular diseases and digestive system diseases. Meanwhile,
another retrospective study has found that 64 patients (46.4%) have
more than one chronic diseases, while 14 patients (10.15%) with
diabetes(Wang et al. , 2020). A retrospective, multi-centered
study of 7337 cases of COVID-19 in Hubei Province, China, showed that
patients with type 2 diabetes required more medical interventions and
had a significantly higher mortality (7.8% versus 2.7%) and multiple
organ injury than the non-diabetic individuals(Zhu et al. , 2020).
Furthermore, they also suggested well-controlled blood glucose (glycemic
variability within 3.9 to 10.0 mmol/L) was associated with markedly
lower mortality compared to individuals with poorly controlled blood
glucose. In coincidence, the COVID-19 patients with diabetes occurred
hyperglycemia frequently and have higher mortality than patients without
diabetes among 1122 patients reported in the United States(Bode et
al. , 2020). These evidences indicated diabetic patients are likely to
develop into severe cases once infection of SARS-CoV-2 occurs. ACE2
modulated the expression of neutral amino acid transporter on the
insulin secretion pancreatic β-cells and the growth of pancreatic islet
cells(Kuba et al. , 2010). The diabetic mice model expressing
human ACE2 increased in the production of insulin, while decreased in
apoptosis of pancreatic islet(Lu et al. , 2014). Local and
systemic Ang Ⅱ levels were regulated by ACE2, which was reduced in
diabetic tissues(Tikellis et al. , 2012). Moreover, the ratio of
ACE/ACE2 was positively correlated with the systolic pressure, the
fasting blood glucose level, serum creatine in the patients(Mizuiriet al. , 2008). However, ACE2-deficient mice showed impairments in
islet dysfunction and abnormality in glucose tolerance(Bindom et
al. , 2010). Moreover, Endogenous ACE2 seems to have an effect on the
adaptive β-cells hyperinsulinemic response, as seen in a diet-induced
diabetes type 2 model, in which β-cells mass and proliferation were
significantly reduced in ACE2-/y mice compared with controls(Shoemakeret al. , 2015). Interestingly, treatment with rhACE2 prevented
from diabetic nephrology(Tikellis et al. , 2003). These studies
suggested the relationship between ACE2 expression and hyperglycemia,
while it still needed to explore the mechanism that COVID-19 patients
are more prone to hyperglycemia in the status of ACE2 down-regulation.