Treatment Tips as COVID-19 Complicates CVD Management in Diabetes

Miriam E. Tucker

May 22, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape' Coronavirus Resource Center.

A new article outlines the many ways in which the COVID-19 pandemic necessitates new considerations beyond traditional cardiovascular risk management in people with diabetes and offers suggestions for an optimal approach for those hospitalized with the infection.

"COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes," say Antonio Ceriello, MD, head of the diabetes department at IRCCS MultiMedica, Milan, Italy, and colleagues. All authors are members of the Diabetes and Cardiovascular Disease Study Group of the European Association for the Study of Diabetes (EASD).

And although it doesn't appear that people with diabetes are more prone to SARS-CoV-2 infection, "there is no doubt that when infected, they are more prone to have serious complications or to die," they note.

Indeed, new data from the UK have this week confirmed that finding.

"More than diabetes itself, the problem might be related to the level of the metabolic control and the presence of comorbidities, particularly cardiovascular disease (CVD)," Ceriello and colleagues say.

"Therefore, it is easy to understand why the prevention/management of CVD in COVID-19 is considered a key issue today," they note in their article, part of a special issue on COVID-19 in diabetes published in Diabetes Care.

Initial Evaluation: What Was There Before? What Did the Virus Cause?

The article provides a suggested flowchart for patients hospitalized with COVID-19, beginning with evaluation of risk factors including diabetes, hypertension, obesity, and smoking.

If the patient has any of those, the advice is to evaluate the individual for lung disease, coronary artery disease, heart failure, arrhythmias, transient ischemic attack/stroke, peripheral arterial disease, and chronic kidney disease.

Many of those conditions are commonly associated with diabetes, but severe SARS-CoV-2 infection can also precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias, as well as acute respiratory distress syndrome. Thus, the authors point out, "If any organ damage is found, this may be pre-existing and aggravated," or alternatively it could have been "induced by COVID-19."

Similarly complicated is the recommended assessment of biomarkers of organ damage, given that increased levels of D-dimer, brain natriuretic peptide (BNP)/N-terminal prohormone BNP, troponin, and inflammatory cytokines can be present in diabetes, even without concomitant infection.

"This may imply that the use of these biomarkers to follow the evolution of COVID-19 in people with diabetes needs a careful evaluation," Ceriello and colleagues write.

In addition to the aforementioned biomarkers, the panel also recommends assessment of blood gas, hyperglycemia, A1c, and creatinine/estimated glomerular filtration rate.

Pharmacologic Treatment: How Are the Drugs Interacting With the Virus?

The article addresses the numerous unknowns about the safety — and possible benefits — of antihypertensive and glucose-lowering medications in patients with COVID-19.

For now, the recommendation is to continue angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, despite the theoretical concern that the drugs increase the expression of ACE2 receptors, which SARS-CoV-2 binds to in order to enter host cells.  

And, Ceriello and colleagues point out, there is some animal evidence that glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, pioglitazone, and metformin might all also promote ACE2 activity. At the same time, both SGLT2 inhibitors and GLP-1 receptor agonists have anti-inflammatory activities, which might be beneficial for patients with COVID-19.

Still several expert groups in diabetes have previously advised that SGLT2 inhibitors and metformin be stopped in all patients hospitalized with COVID-19.

Similarly confounding, dipeptidyl peptidase 4 (DPP-4) inhibitors have been linked to an increased risk for certain infections, but at the same time also have anti-inflammatory properties.

In general, for patients not in the intensive care unit, the panel recommends DPP-4 inhibitors, GLP-1 agonists, or subcutaneous insulin as preferred glucose-lowering options over the other medications.

They also advise abstaining from steroids, appropriate anticoagulation, and use of continuous glucose monitoring if available.

In the ICU: Intravenous Insulin and Other Considerations

For patients in the ICU, the recommendation is to stop all oral glucose-lowering agents and subcutaneous insulin, and switch to intravenous insulin for glucose control, using exact dosing with a perfusion device aiming at a blood glucose target of 140-180 mg/dL (7.8-10.0 mmol/L).

Noting that high glycemic variability itself is predictive of high ICU mortality, the authors state, "it has already been suggested that the management of glucose variability has to be part of the more comprehensive approach to the management of hyperglycemia today: it seems that this must be urgently applied in ICUs."

"Even though we understand that in such a critical situation this request is not easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act."

The document advises blood pressure targets of 125-140 mmHg systolic and < 85 mmHg diastolic, and statin use informed by monitoring plasma creatine kinase. 

The authors also recommend consideration of thrombotic risk and acute heart failure.

They conclude, "Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic similar to influenza because of genetic mutation. Therefore, we should be ready for the re-emergence of COVID-19."

"Considering that CVD represents the leading epidemic in diabetes, it is mandatory to set long-term strategies not only aiming to avoid the infection but also to have people with diabetes in the best CV condition if infected."

The authors have reported no relevant financial relationships.

Diabetes Care. Published online May 14, 2020. Full text

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