COVID-19 and Diabetes: Linking Mechanisms
and Disease Management
The outbreak of coronavirus disease (COVID-19) has led to a global health crisis, with the infection rate still seeing an exponential rise. As of 09-Oct-2020, there are 36 million confirmed cases with 10,64,838 deaths.
COVID-19 affects people of all ages. However, persons with pre-existing co-morbidities, such as diabetes mellitus, respiratory problems, hypertension, cardiac disease, and cancer are at higher risk. Of these conditions, diabetes is of significant concern, given its high prevalence in the adult population (9.3% worldwide, as of 2019). Nearly half a billion people are affected by diabetes, and it is the leading non-communicable disease worldwide.
On a global level, nearly 20–50% of COVID-19 patients are diabetic, as reported in a recent study published in ‘The Lancet Diabetes & Endocrinology’. Pooled analysis of data from several studies reveal diabetics are at greater risk to COVID-19 infection with higher mortality rates compared to non-diabetics (28.5 vs. 13.3%). In fact, diabetes was also one of the primary risk factors known to be associated with detrimental health outcomes during previous epidemics, namely SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
Reckoning both the global prevalence of diabetes and high transmission rate of the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, the virus causing COVID-19], it is imperative for the physicians to understand the possible mechanisms which pre-dispose diabetics to severe outcomes of COVID-19. Furthermore, the risk of progression of COVID-19 multiplies when other associated factors such as hypertension and obesity co-exist with diabetes.
Therefore, understanding the interwoven mechanisms of COVID-19 and diabetes, could collectively assist the physicians on effective management of these co-existing conditions, and enhance the public awareness in order to prevent devastating outcomes.
Diabetes and COVID-19: Interacting mechanisms
Diabetes mellitus is characterized by elevated blood glucose levels with serious impact on multiple organ systems. Uncontrolled glycemic status with impaired immune mechanisms expose diabetics to increased risk of infections, including — as in present context — COVID-19. As a result, the first line of innate and humoral defenses are rendered ineffective in response to SARS-CoV-2, triggering an exaggerated pro-inflammatory cytokine reaction. This is plausibly explained by the reciprocal effects of SARS-CoV-2 and high blood glucose levels observed in diabetics on ACE2 (Angiotensin Converting Enzyme 2) receptor pathways.
ACE2 receptor is an enzyme present on the cell membrane of multiple organs, namely lungs, small intestine, kidneys, heart, blood vessels, pancreatic beta cells, skeletal muscle, and adipose tissue. These receptors mediate normal physiological functions such as blood pressure regulation, metabolism including glucose homeostasis, and inflammation.
Receptors also act as entry points for SARS-CoV-2. In an acute hyperglycemic state, as seen in diabetics, ACE2 activity is up-regulated, enabling entry of the virus into the host cell. Upon entry, the virus down-regulates the ACE 2 receptor and impairs blood glucose metabolism with exaggerated inflammation. Imbalance of ACE2 activity in pancreatic cells causes beta cell dysfunction, resulting in an acute hyperglycemic state. Thus, COVID-19 infection in diabetics follows a vicious cycle, reinforcing negative effects, leading to devastating outcomes such as cytokine storm, lung injury, acute respiratory distress syndrome (ARDS), multiorgan failure, and death.
Interplay between diabetes-associated co-morbidities and COVID-19
Diabetics often have other co-morbidities such as cardiovascular diseases, hypertension, and obesity. The pulmonary complications of COVID-19 are exacerbated in patients with these co-morbidities.
SARS-CoV-2 binds to the ACE2 receptor and directly affects the blood vessels, heart, and adipose tissue. The protective effects of ACE2 in blood pressure regulation are counteracted by SARS-CoV-2, causing detrimental effects on the cardiovascular system.
In addition, drugs used in the treatment of hypertension (for example, angiotensin receptor blockers, ACE inhibitors) up-regulates the ACE2 activity in target cells, enhancing the risk and severity of COVID-19 infection. Pulmonary complications of COVID-19, such as pneumonia and ARDS reduce the oxygenating capacity of the lungs. Consequently, the cardiac workload increases, thereby affecting the heart and blood vessels.
Abdominal obesity is another noteworthy feature seen in diabetics. Chronic low-grade inflammation, a key aspect of abdominal obesity induces abnormal secretion of adipokines, cytokines, and interleukins. They attenuate immunoregulatory mechanisms and trigger a cytokine storm in COVID-19 infected patients. This cytokine response in turn induces insulin resistance and worsens the glycemic status, leading to diabetic complications.
Management of COVID-19 infection in diabetics: General considerations
Management of co-existent diabetes and COVID-19 is challenging. Majority of the patients require extensive hospitalization and intensive care in order to prevent serious and fatal outcomes. In general, inadequate intake of food and water during intercurrent illness like COVID-19 infection can lead to hypoglycemia and dehydration. Diabetes further accentuates hypoglycemia and electrolyte disturbances in dehydrated patients with infection. Moreover, use of drugs like glucocorticoids for respiratory problems in COVID-19 alters blood glucose levels.
Therefore, it is crucial for diabetics to maintain optimal glycemic control with frequent blood glucose monitoring which would help to minimize the risk of diabetic complications. Adequate hydration, symptomatic treatment of infection, and strict adherence to general preventive measures such as social distancing and hand hygiene, are necessary to combat the spread of COVID-19. Concurrently, compliance to anti-diabetic therapies, regular physical activity and a healthy diet minimize severe disease outcomes in patients with diabetes.
Conclusion
Based on the above views, people with diabetes and other co-morbidities are more vulnerable to COVID-19 infection. The role of ACE2 receptors explains the increased risk. Co-morbidities such as cardiovascular diseases, hypertension, and obesity magnify the severity of COVID-19 infection in diabetics. Hence, vulnerable people should be more vigilant. Strict adherence to social distancing, and hand hygiene measures, as well as ensuring optimal glucose control could prevent disease-associated complications.
