COVID-19: Considerations of Diabetes and Cardiovascular Disease Management

We have learned in this “Corona Virus Disease 2019 (COVID-19)” pandemic that, as usual, people with diabetes pay a very high prize due to their disease.

Evidence clearly shows that people with diabetes are prone to be infected by the “Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2)” if not in good glycemic control,¹ as well as are more susceptible to the development and a severe course of COVID-19.¹ Moreover, another aspect to underline is that by having several comorbidities, particularly cardiovascular complications and nephropathy, people with diabetes are also more likely to die from COVID-19.²

It is clear today, even more than in the past, that it is mandatory to maintain people with diabetes in good glycemic control as well as their cardiovascular system and their kidneys in good condition: this way, they are in best possible condition for COVID-19, if affected. In this regard, there are some issues on the horizon which must be elucidated as soon as possible. Angiotensin-converting enzyme-2 (ACE2) has been proposed as receptor for SARS-CoV-2.³ It has recently been hypothesized that sodium/glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), pioglitazone, and even insulin might induce an overexpression of ACE2,⁴ thus increasing the risk for more serious consequences in people with diabetes, if infected. On the other hand, the benefit of both GLP-1RAs and SGLT-2i in the prevention of cardiovascular and kidney disease is well known.⁵ At the same time, it is also worth to mention that pioglitazone, dipeptidyl peptidase-4 inhibitors, SGLT-2is, GLP-1RAs, and also insulin have shown anti-inflammatory activity, which could be very helpful in the course of COVID-19.⁶ In our opinion, this issue must be addressed as soon as possible, as already done for ACE inhibitors and angiotensin receptor blockers.⁷

Another important aspect is the treatment of people with diabetes during a possible stay in intensive care unit (ICU). Evidence largely shows that tight glucose control, particularly avoiding hypoglycemia and glycemic swings, improves the prognosis predominantly by reducing the risk of cardiovascular complications.⁸ The fact that large glycemic variability per se is predictive of high ICU mortality also deserves attention.⁸ Experience shows that the management of glycemia is insufficient during this pandemic and that there is an urgent need to improve the awareness on this issue.^9,10 It is highly surprising that very recent guidelines, specifically developed for the management of COVID-19 in the ICU, do not consider neither the presence of diabetes as comorbidity nor the proper management of hyperglycemia.¹¹

We predict that in future it is likely, unfortunately, that humanity will have to face recurrent phases of SARS-CoV-2 infections. Considering that cardiovascular disease represents the leading epidemic in diabetes, it is mandatory to develop long-term strategies, which not only aim at the prevention of the infection but also to have people with diabetes in best cardiovascular conditions, if infected. Implementing the current guidelines on the prevention of cardiovascular disease in diabetes therefore is a very urgent action, now more than ever. The role of telemedicine for online advice for drug dosage adaptation needs, or any other remotely manageable medical emergencies, also seems essential today.

We also have to keep in mind that diabetes management is not easy to handle in acutely ill people. Thus, when having to face high glucose levels, as expected from the impact of an infection per se when on any unstable metabolic control, it can happen that patients are suddenly switched to insulin—although evidence suggests that insulin treatment might be not safely managed in such situations,^12,13 leading to high glucose variability.

Glucose variability during hospitalization worsens the prognosis.⁸ This means that, despite trying to do their best for infected people, COVID-19 units may unintentionally make the disease even more serious due to high glycemic variability. It has already been suggested that the management of glucose variability has to be part of a more comprehensive approach to the management of hyperglycemia today—it looks like this has to be urgently applied in ICUs.^8,14 Even though we understand that in such a critical situation this request may be very hard to implement, we also believe that the best possible action to prevent worse outcomes is essential in any medical act.

For this reason, despite being fully aware that support of vital functions represents the primary goal for physicians taking care of COVID-19 patients, we suggest continuous subcutaneous glucose monitoring to be made available in as many settings as possible.

In conclusion, the world has changed and we will probably need to change our habits. Accordingly, also diabetes management has to change to face the new challenges raised with the appearance of SARS-CoV-19.