Parallel pandemics: COVID-19 and diabetes
One of the most powerful sessions at this year’s EASD Annual Meeting concerned COVID-19. First up was Professor Juliana Chan, whose Hong Kong registry has proved such a vital resource for understanding the relationship between COVID-19 and diabetes. Here was a masterful survey of the available evidence in this sadly burgeoning field. Professor Chan began by pointing out some of the similarities between COVID-19 and diabetes: both global pandemics of course; both silent killers; both attributable to changes in ecosystem and human behaviour; both capable of overwhelming healthcare systems. To tackle each requires governmental, intersectoral and individual action.
Both are also potentially preventable and treatable, a point which has particular significance when you consider the effect of hyperglycaemia on how well people with diabetes who become infected fare – put starkly, people with well-controlled diabetes are 80% more likely to survive infection than people with poor blood glucose control. Obesity, ethnicity and low socio-economic status, with its attendant difficulties of health literacy and poor access to care, also play their part in the disparity of outcomes – forming a synergistic interaction which Professor Chan termed ‘syndemic’.
But what about diabetes type? Professor Chan cited a UK study in the Lancet (Barren, et al.), which showed that of in-hospital deaths from COVID-19 in the UK, only 1.5% had type 1 diabetes; as many as 31.4% had type 2. However, after adjustment for CVD and heart failure, infected people with type 1 were at higher risk of in-hospital death (odds ratio 3.51, as compared to 2.03 for people with type 2). Looking at links between COVID-19 outcomes and diabetic comorbidities, cardiovascular health was important but kidney disease more strikingly so – for type 1 and type 2 patients alike.
Treatment for kidney disease, specifically use of ACE2 inhibitors, has attracted a lot of attention in relation to COVID-19 because of the crucial role of ACE2 receptors in the SARS-CoV-2 infection pathway, with some suggesting that use of ACE2 inhibitors might facilitate infection. Professor Chan insisted that since March, when the Lancet paper first triggered that debate, more evidence has emerged to show neutral or even beneficial effects of ACE inhibitors. (She recommended their continued use in high-risk individuals.)
This point was reiterated by the next speaker, Professor Daniel Drucker, whose presentation asked whether shared pathways in COVID-19 and type 2 diabetes had therapeutic implications. His fascinating talk underlined the apparently contradictory impulses that have characterised reporting on this topic, by which diabetes-related treatments and receptors with inflammation-regulating characteristics – which might therefore be seen as potential allies against the effects of COVID-19 – are also suspected as possible targets of the virus. DPP4s are a case in point, although Professor Drucker was quick to point out that although DPP4 receptors are implicated in MERS-CoV infection, there is no proof that they act as receptors for SARS-CoV-2. Evidence from flu and HIV studies suggests they may have anti-inflammatory benefit, but the data is inconclusive. So, while DDP4s are safe to use (there is no evidence they increase inflammation in infected patients), Professor Drucker cautioned against presuming any special benefit in people with COVID-19. Metformin is likely to have stronger anti-inflammatory benefit than DPP4, although it is cautioned against in certain COVID-19 patients owing to the dangers of DKA and lactic acidosis during illness. Insulin also: another treatment with potential anti-inflammatory properties, yet some studies have suggested higher morbidity among insulin-treated COVID-19 patients. Professor Drucker warned that the meaning of these data is far from clear: the fact patients are on insulin may reflect greater severity of diabetes. One thing is certain, however: the importance of optimal glycaemic control. Put simply, people with better glycaemic control probably have better immune responses to the virus. Treating glucose is an immediate and modifiable risk factor that can be addressed quickly in response to the pandemic – if people have excellent diabetes control, they are probably not at such a high risk.
This point was taken up by the final speaker, Professor Catarina Limbert. Focusing on type 1 diabetes, Professor Limbert echoed the first speaker with regards to the tighter association between COVID-19 mortality and type 1, as compared with type 2 diabetes. But she refined the point. Only those with HbA1c greater than 10% had significant mortality risk. Longer diabetes duration and more frequent comorbidities among the type 1 patients were also significant, along with age (patients over 50 were at greater risk of worse outcomes from COVID-19).
Professor Limbert’s specialism is with children and young people with diabetes, an age group notoriously less vulnerable to SARS-CoV-2 infection. Data from the USA shows that only 1.7% of lab-confirmed COVID-19 cases are among children under 18. Exactly why remains a matter of speculation, but Professor Limbert pointed to ACE2 gene expression, which is lower in younger age groups, specifically in the nasal epithelium – the first binding point for SARS-CoV-2 in the body. But this does not mean that children with type 2 have come through the pandemic unscathed. A number of national reports show steep increases in DKA and severe DKA among young people with type 1 diabetes during this period (by as much as 84% in Germany) – probably brought about, Professor Limbert suggests, by delayed diagnosis due to fear of COVID-19, reduced services and difficulties accessing routine clinical care (Italy alone has seen around an 80% decrease in paediatric emergency visits).
Another concern in this field is that COVID-19 infection might trigger type 1 diabetes, whether via diabetogenic aspects of the virus itself or the cytokine storm it can generate. For those caring for children this may not be concerning, given their low infection rate or propensity to mild or asymptomatic manifestation. The psychological stresses associated with the pandemic, against which youth offers no such protection, might also have a triggering effect. On the whole, however, Professor Limbert considered the scenario of a COVID-19-linked spike in type 1 unlikely.
She concluded her presentation on a positive note, celebrating the better autonomy and reduced burden of routine care brought in the wake of a necessary switch to telemedicine. But even silver linings can come with caveats: although studies suggest improvements in glycaemic control for many patients during lockdown, we should be wary of ‘bubbles’. Given disparities in access, skills, etc., such improvements are unlikely to occur evenly across the type 1 population. We need to take action to mitigate these disparities. Funding is required to improve telemedicine. And now, more than ever, IT specialists are needed as members of the diabetes team.
For more on diabetes and COVID-19, see our series of COVID-19 tutorials.
The opinions expressed in this blog are those of the author, Dr Eleanor D Kennedy.
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Sessions at the EASD 56th Annual Meeting 2020
COVID-19 and diabetes
Juliana Chan. COVID-19 and diabetes: what is the evidence?
Daniel Drucker. COVID-19 and type 2 diabetes: do shared pathways have therapeutic implications?
Catarina Limbert. What have we learned from COVID-19 in persons with type 1 diabetes?