More Guidance on 'Vulnerable Subgroup' With Diabetes and COVID-19

Miriam E. Tucker

April 28, 2020

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

An international panel of diabetes experts has published practical recommendations for managing diabetes in patients with COVID-19 both in and out of the hospital setting.

The aim, they say, is to emphasize "the multiple challenges" healthcare professionals "from practitioners to intensive care staff might face in the management of...this vulnerable subgroup...of patients with diabetes...at risk of, or with, COVID-19."

The recommendations were published online April 23 as a "personal view" in Lancet Diabetes & Endocrinology by a 19-member panel led by Stefan R. Bornstein, MD, of the Helmholtz Center Munich and Technical University of Dresden, Germany.

Other panelists include individuals from Europe, the United States, Asia, Australia, and South America.

Diabetes is generally a major risk factor for the development of severe pneumonia and sepsis due to virus infections, and data from several sources suggest the risk for death from COVID-19 is up to 50% higher in people with diabetes than those without, they say.

Evidence also suggests risks associated with COVID-19 are greater with suboptimal glycemic control, and that the virus appears to be associated with an increased risk for diabetic ketoacidosis and new-onset diabetes.

Based on these findings — and initial advice from the American Diabetes Association, among others — as well as a literature search for a combination of appropriate terms on PubMed between April 29, 2009, and April 5, 2020, the panel made the following consensus recommendations.

Outpatient and Inpatient Care

1. Infection prevention and outpatient care:

  • Sensitization of patients with diabetes to the importance of optimal metabolic control. This is particularly important in individuals with type 1 diabetes, who should be reminded of home ketone monitoring and sick-day rules.

  • Optimization of current therapy, if appropriate.

  • Caution with premature discontinuation of established therapy.

  • Use of telemedicine and connected health models, if possible, to maintain maximal self-containment.

2. Monitor for new-onset diabetes in all patients hospitalized with COVID-19.

3. Management of infected patients with diabetes (intensive care unit):

  • Plasma glucose monitoring, electrolytes, pH, blood ketones, or β-hydroxybutyrate.

  • Liberal indication for early intravenous insulin therapy in severe disease courses (acute respiratory distress syndrome, hyperinflammation) for exact titration, avoiding variable subcutaneous resorption, and management of commonly seen very high insulin consumption.

4. Therapeutic aims:

  • Plasma glucose concentration: 4-8 mmol/L (72-144 mg/dL) for outpatients or 4-10 mmol/L (72-180 mg/dL) for inpatients/intensive care, with possible upward adjustment of the lower value for frail patients to 5 mmol/L (90 mg/dL).

  • A1c < 53 mmol/mol (7%).

  • Continuous glucose monitoring/flash glucose monitoring targets: Time-in-range (3.9-10 mmol/L) > 70% of time (or > 50% in frail and older people).

  • Hypoglycemia < 3.9 mmol/L (< 70 mg/dL): < 4% (< 1% in frail and older people).

Medications: Stop Some, Caveats for Using Others

Regarding medications, the panel advises that both metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors be stopped in patients with COVID-19 and type 2 diabetes to reduce the risk of acute metabolic decompensation.

For both drug classes, concerns include increased risks for dehydration, acute kidney injury, and chronic kidney disease, so close monitoring of renal function is recommended.

Metformin also increases the risk for lactic acidosis, and SGLT2 inhibitors increase the risk for diabetic ketoacidosis.

Metformin and SGLT2 inhibitors should not be discontinued prophylactically in outpatients who don't have evidence of COVID-19.

Both glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors can be continued, with the latter generally being well tolerated. However, patients taking GLP-1 agonists should be carefully monitored for dehydration, and adequate fluid intake and regular meals encouraged.  

Insulin therapy should never be stopped and may need to be started in new-onset patients or those with hyperglycemia after being taken off other agents.

Blood glucose monitoring should be encouraged every 2 to 4 hours or using continuous glucose monitoring. Insulin dose should be adjusted based on need, which can be quite elevated in people with COVID-19. Intravenous insulin infusion may be necessary.

Use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be continued; evidence to date is reassuring on this issue, and all major cardiology societies recommend patients remain on these agents.

Statin use should also be maintained, "because of the long-term benefits and the potential for tipping the balance towards a 'cytokine storm' by rebound rises in interleukin(IL)-6 and IL-1β if they were to be discontinued," Bornstein and colleagues write.

Lastly, the experts say, "Considerable care is required in fluid balance as there is a risk that excess fluid can exacerbate pulmonary edema in the severely inflamed lung."

Furthermore, potassium balance needs to be considered carefully in the context of insulin treatment, "as hypokalemia is a common feature in COVID-19 (possibly associated with hyperaldosteronism induced by high concentrations of angiotensin II) and could be exacerbated following initiation of insulin."

Other Clinical Considerations: Screen for Hyperinflammation

Because patients with type 2 diabetes and fatty liver disease may be at increased risk for cytokine storm and severe COVID-19 disease, screening for hyperinflammation is recommended.

Screening includes looking for laboratory trends (eg, increasing ferritin, decreasing platelet counts, high-sensitivity C-reactive protein, or erythrocyte sedimentation rate), which are important and could also help identify subgroups of patients for whom immunosuppression (steroids, immunoglobulins, selective cytokine blockade) could improve outcomes.

Despite its advantages in patients with type 2 diabetes and obesity, elective metabolic surgery should be postponed during the COVID-19 outbreak.

Because SARS-CoV-2 can induce long-term metabolic alterations in patients who have been infected, careful cardiometabolic monitoring of patients who have had COVID-19 is advised.

In conclusion, the panel stress that "all our recommendations and reflections are based on our expert opinion, awaiting the outcome of randomized clinical trials."

"Executing clinical trials under challenging circumstances has been proven feasible during the COVID-19 pandemic...Investigating if some of the various management approaches would be particularly effective in managing diabetes in a COVID-19 context...will be important."

Bornstein has reported no relevant financial relationships. An author has reported serving on advisory boards for Novo Nordisk, Abbott, and Medtronic. The other authors have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published April 23, 2020. Full text

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