Covid-19 and Diabetes – A Bidirectional Relationship?
Diabetes and Covid-19 are two devastating pandemics, which have been frequently associated in the recent months. They have very different characteristics: Covid-19 is an acute and communicable illness, while diabetes is a chronic and noncommunicable disease. And yet, there is a close connection between them.
COVID-19 is a new pathology, caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus), a new coronavirus that was declared pandemic by the WHO on March 11, 2020. Coronavirus is a family of viruses that includes SARS and MERS (Middle-East Respiratory Syndrome). There is an increasing evidence of human to human transmission .
The first infection cases (a new form of atypical pneumonia) emerged in Wuhan, Hubei region, China, in December 2019. More specifically, it seems that the starting point was the live animals section of the Huanan Wholesale Market [1,2].
The epidemiological status is continuously changing. Here is a global and national overview, updated on April 20, 2020: Globally, a number of 2,408,359 patients were diagnosed with Covid-19, of whom 26.12% recovered, 6.85% died and 67.01% are currently infected, while 54,216 were in a severe and critical state (2.25% of the total). At the same date in Romania, there were 8,746 diagnosed cases, of which 21.63% recovered, 5.15% died and 73.21% are currently infected, 256 (2.92%) being severe and critical .
The data regarding the association of Diabetes with Covid-19 is controversial. There is a perception that the risk for both infection and severe disease is higher in patients with diabetes; it seems that diabetes increases the hospitalization and mortality rate of patients with Covid-19.
It is possible that a good glycaemic control may reduce the risk, though without eliminating it completely [4-7]. This finding is consistent with the association between diabetes and excess mortality caused by any acute and chronic condition, including infections .
There are a number of risk factors that increase Covid-19 morbidity and mortality: people aged 65 and older or people of any age who have serious underlying medical conditions, like: severe obesity (BMI≥40kg/m2), diabetes, chronic lung disease including asthma, people in nursing homes or long-term care facilities, serious heart conditions, hypertension, immunocompromised, chronic kidney disease, liver disease, etc [5,9-11].
The Chinese Center for Disease Control and Prevention, analyzing mortality among 44,672 confirmed cases found the following: total mortality was 2.3%, increasing with age, reaching 8% in people aged 70-79 and 14,8% in people over 80 years old, while skyrocketing to 49.0% among critical cases. Mortality was higher among patients with preexisting comorbid conditions: 10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, 5.6% for cancer .
More relevant, recent data coming from Italy showed that more than two-thirds of COVID-19 patients who died by severe acute respiratory syndrome had diabetes [13,14]. 16% of the patients with severe forms of COVID-19 had diabetes, in contrast to only 5.7% of those with mild forms of the disease .
The possibility of involving several mechanisms that may increase the susceptibility for COVID-19 in patients with diabetes is being discussed: the existence of an increased affinity of the virus towards the cellular receptors and their intracellular entry facilities; cellular receptors are represented by ACE2 (angiotensin converting enzyme 2), expressed in the upper respiratory system, type I and II alveolar epithelial cells in the lungs, the heart, endothelial cells, kidney tubular epithelium, enterocytes, pancreas, liver, gut, etc., partially explaining multiorgan insufficiency in severe forms of infection; increased ACE2 expression in this levels may favor increased cellular binding of SARS-CoV-2 [15-17].
The increase of ACE 2 expression in lungs, kidneys, heart and pancreas has been demonstrated on animal models with diabetes, data which has been confirmed in humans also. On the other hand, some drugs frequently used by patients with diabetes, like GLP-1 receptor agonists, thiazolidinediones, antihypertensives such as ACE inhibitors, statins, up-regulate ACE2. On the contrary, insulin treatment attenuates ACE2 expression, having a possible positive role in patients with diabetes, lowering the risk of infection [17-19].
Increased values of a cellular protease called furin have also been described in diabetes, which facilitates the entry of the virus into the cell, acting on the spike protein . Decreased viral clearance, decreased T cell function, increased susceptibility to hyperinflammation and cytokine storm syndrome: Chen X et al, reported in their study that clearance of SARS-CoV-2 was delayed in patients with diabetes, but it is necessary fortheir results to be confirmed in larger studies.
In diabetes, a number of disorders of immune defense occur: it inhibits neutrophil chemotaxis, phagocytosis, intracellular killing of microbes. In these patients, an initial delay in the activation of Th1 cell-mediated immunity and a late hyper-inflammatory response is often observed [17,21].
The presence of CVD, beside hypertension, and severe obesity (BMI≥40kg/m2) increases morbidity and mortality in patients with diabetes and COVID-19 .
How does SARS-CoV-2 infection influence diabetes? If diabetes can influence Covid-19 morbidity and mortality, greater attention should be paid to how SARS-CoV-2 infection can affect the evolution of diabetes.Hepatic and pancreatic β-cells ACE2 receptors for SARS-CoV-2 may facilitate insulin resistance and β-cells destruction, worsening hyperglycemia at least during the acute infection and increasing the number of people with diabetes. In the long term, however, autoimmune destruction of the pancreatic β-cells may occur, in predisposed subjects, as described for other viruses, which may induce insulin-dependent diabetes .