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.