When pandemics collide: COVID-19 and diabetes
‘Two pandemics in collision: COVID-19 and diabetes’ was the title of a presentation by Paul Zimmet, Professor of Diabetes at Monash University in a joint session between The Lancet Diabetes & Endocrinology and the 18th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) in December. Professor Zimmet began by making the important point that it’s not only these two pandemics colliding; other chronic-disease pandemics, such as heart disease and obesity, are also in the fray.
When people with these non-communicable diseases (NCDs) are exposed to communicable diseases (CDs) such as COVID-19, outcomes tend to be worse for them than for the general population. With that in mind, Professor Zimmet called for urgent action across the world to bring down NCD rates through prevention and control.
With regard to diabetes, he outlined the major risk factors for patients who get COVID-19 that make severe disease and mortality more likely, with type 1 diabetes having a greater risk of mortality than type 2. These are wide ranging, from immune dysfunction and inflammation, oxidative stress and associated obesity, to related comorbidities such as cardiovascular disease, fatty liver and hypertension.
Of particular interest to Professor Zimmet are the reported cases of new-onset diabetes potentially caused by COVID-19. His team at Monash University has collaborated with King’s College London to establish a register, the CoviDiab Registry, to document cases of new-onset diabetes in patients with COVID-19 and will follow them longitudinally. To explain why, he drew fascinating parallels with the 2003 SARS outbreak, highlighting a study of 39 SARS patients who had no previous diabetes. Twenty had diabetes during hospitalisation but only two still had it after three years, suggesting that it may not persist in some people.
As there is with the SARS-CoV-2 virus, there was also an angiotensin-converting enzyme 2 (ACE2) receptor link with SARS. Professor Zimmet highlighted that ACE2 expression in the endocrine part of the pancreas suggested that SARS entered islets using ACE2 and damaged them, causing acute diabetes. The work now is to establish exactly what role ACE2 plays in the current pandemic.
He was followed by Professor Stefan Bornstein, Chair of Internal Medicine at University Clinic Carl Gustav Carus in Dresden and Transcampus Dean at King’s College London, who went into more detail about ACE2 hypotheses and the research that’s being done to help uncover the full story.
Two slides outlined two mechanisms that might play a role in COVID-19. Firstly, the SARS-CoV-2 virus is hijacking an endocrine pathway that plays a crucial role in blood pressure regulation, metabolism and inflammation to gain entry into its target cells. ACE2 has been identified as the receptor for the coronavirus spike protein – ACE2 has protective effects against inflammation, but COVID-19 reduces its expression, thereby inducing cellular damage, hyperinflammation and respiratory failure.
Secondly, acute hyperglycaemia has been shown to upregulate ACE2 expression, which might facilitate viral cell entry. However, chronic hyperglycaemia downregulates ACE2 expression, making the cells vulnerable to the damaging inflammatory effects of the virus. This is a vicious cycle that could lead to more severe disease. In addition, there is clear evidence that SARS-CoV-2 directly affects pancreatic cells, including beta cells. While being at pains to point out that these findings have not been proven in humans, he touched on the fact that COVID-19 could lead to new-onset diabetes.
He acknowledged that there may also be a non-ACE2 mechanism for the virus to enter the cells. Another potential is the DPP-4 enzyme, which is often targeted with medication in type 2 diabetes.
The ‘good news’ part of his presentation is that well-controlled blood glucose is key to improving the outcome of patients infected with SARS-CoV-2 and this is a way that clinicians can help their patients both in outpatient clinics before they may become infected with COVID-19 to give them the best chance of a positive outcome if they do, or afterwards in a home or hospital setting.
We also know the characteristics of diabetes patients who may do better and those who may have worse outcomes, such as having higher BMI and being elderly. He presented useful treatment guidelines that were published in The Lancet Diabetes & Endocrinology for both preventative outpatient care (for example, promoting the importance of good metabolic control) and in-patient/ICU care including close glucose monitoring and the use of early insulin therapy. The full version of this is well worth listening to or reading in the journal if you work in this area.
The final talk in the session covered Obesity and Metabolic Surgery During and Beyond COVID-19, which we’ll discuss in our next blog.
New EASD e-Learning courses on recent literature around diabetes and COVID-19 are currently in development and will be launching in 2021.
The opinions expressed in this blog are those of the author, Dr Eleanor D Kennedy.