In March, the Centers for Disease Control and Prevention (CDC) announced that it would prioritize all patients with diabetes for COVID-19 vaccinations—a decision that was applauded by the American Diabetes Association which sought to reverse a previous guidance that didn’t prioritize all diabetes patients.

“The updated recommendation is a welcome change for the nearly 1.6 million Americans who have type 1 diabetes, many of whom were left behind—even if inadvertently—by the CDC’s previous guidance,” said Tracey D. Brown, the chief executive officer for the American Diabetes Association (ADA). “We know people with diabetes account for nearly 40 percent of all COVID-19 related deaths. Having the CDC acknowledge the serious risk to all people with diabetes from COVID-19 will go a long way toward boosting increasing access to the vaccine for our community at a critical time. It is crucial that remaining states follow suit. The science and the CDC recommendation leave no doubt that all people with diabetes should be prioritized equally.”

As part of the CDC’s phase 1c COVID-19 vaccine rollout that began in March, the CDC recommends that all patients between 16 and 64 years old with underlying medical conditions receive a COVID-19 vaccine. In addition to patients with type 1 or type 2 diabetes, the list includes patients with cancer, chronic kidney disease, chronic lung diseases (including chronic obstructive pulmonary disease, asthma, interstitial lung disease, cystic fibrosis, and pulmonary hypertension), dementia or other neurological conditions, Down syndrome, cardiovascular conditions (such as heart failure, coronary artery disease, cardiomyopathies or hypertension), HIV infection, patients with immunodeficiency, liver disease, obesity, sickle cell disease or thalassemia, stroke or cerebrovascular disease, among other conditions.


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Clinicians should use their judgment and may recommend patients for vaccination even if their underlying medical condition is not included on the list. “Studies have shown that COVID-19 does not affect all population groups equally. The risk of severe COVID-19 increases as the number of underlying medical conditions increases in an individual. Some chronic medical conditions occur more frequently or at a younger age in racial or ethnic minority populations,” the CDC stated in a report published on its website.

According to a study published in JAMA Network Open by Ning Rosenthal, MD, MPH, PhD, of Premier Applied Sciences, North Carolina, 70.1% of inpatients and 25.1% of outpatients with COVID-19 had at least one comorbidity with the most common being hypertension (30,236 [46.7%]), hyperlipidemia (18,744 [28.9%]), diabetes (18,091 [27.9%]), and chronic pulmonary disease (10,434 [16.1%]). Old age of at least 80 years was found to be the risk factor most often associated with death which applied to 20.3% of inpatients in the Rosenthal et al. study.

Still, pre-existing comorbidities were associated with a higher risk of mortality for patients who were admitted to the hospital for COVID-19 treatment. Rosenthal et al. found that COVID-19 patients with a metastatic solid tumor had a 57% higher risk of inhospital mortality as compared to patients with a history of myocardial infarction (47% increase), patients with cerebrovascular disease (39% increase), congestive heart failure (37% increase), hemiplegia (34% increase), any malignant neoplasm (27% increase), dementia (20% increase), diabetes (20% increase), chronic pulmonary disease (16% increase), and hyperlipidemia (11% increase). The presence of multiple comorbidities was associated with a higher risk of in hospital mortality.

In a review of 235 studies on COVID-19 and its effect on patients with pre-existing comorbidities, the CDC concluded that based on the meta-analysis and systematic reviews included in the CDC review, only nine conditions were found to have a significant association with risk of severe COVID-19 illness. These include cancer, cerebrovascular disease, chronic kidney disease, COPD (chronic obstructive pulmonary disease), diabetes mellitus (type 1 and type 2), cardiovascular conditions (such as heart failure, coronary artery disease, or cardiomyopathies), obesity (BMI ≥30 kg/m2), pregnancy, and a history of smoking or current smokers. Studies that identified other comorbidities said to be a high risk for mortality or severe illness were mostly observational or as a result of case reports.

THE DIABETES PATIENT

Writing in Acta Diabetolgica in February, Qing Cheng of Huazhong University of Science and Technology in Wuhan, China, diabetes patients may be at higher risk of mortality and more severe COVID-19 prognosis possibly because insulin resistance ultimately stimulates the production of pro-inflammatory cytokines, oxidative stress, and adhesion molecules.

“Infection leads to destruction of pancreatic beta cells, decreased pancreatic insulin content, and changes in the host’s ability to respond normally to glucose tolerance tests,” Cheng et al. wrote in the study.

Drs. Rimesh Pal and Sanjay K. Bhadada—two endocrinologist from India—writing in Diabetes & Metabolic Syndrome:  Clinical Review & Reviews, described the physiological disease process between diabetes mellitus and COVID-19 as a “vicious cycle.”

“The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with diabetes mellitus take all necessary precautions and ensure good glycemic control amid the ongoing pandemic,” they wrote.

Pal and Bhadada theorized that “compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and the use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19. On the contrary, direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus.”

A panel of physicians writing in The Lancet in April 2020, issued a set of treatment recommendations for diabetes patients with COVID-19. For out-patient care, they recommend stressing to the patient the importance of achieving optimal metabolic control and they caution against prematurely stopping treatments diabetes patients are receiving.

For in-patient care, they recommend monitoring patients for new onset diabetes in patients who are infected with COVID-19.

For diabetes patients receiving in-patient care for COVID-19, routine monitoring should include plasma glucose monitoring, electrolytes, pH, blood ketones, or β-hydroxybutyrate, the panel wrote.

The ultimate goal for treatment should be:

·  Plasma glucose concentration: 4–8 mmol/L (72–144 mg/dL)

·  HbA1c:† less than 53 mmol/mol (7%)

·  CGM/FGM targets

·  TIR (3·9–10 mmol/L): more than 70% (>50% in frail and older people)

·  Hypoglycaemia (<3·9 mmol/L): less than 4% (<1% in frail and older people)

·  Plasma glucose concentration: 4–10 mmol/L (72–180 mg/dL)

For patients with type 2 diabetes and COVID-19, the panel warns against possible negative drug interactions. Patients taking metformin, for example, may experience dehydration and lactic acidosis so it may be necessary to temporarily stop taking the drug. These patients are at high risk of renal injury so renal function should be monitored.

Insulin therapy should not be stopped for patients with COVID-19 and diabetes. They should monitor blood-glucose every 2–4 hours or follow continuous glucose monitoring practices. Medicines should be adjusted, if appropriate, to reach therapeutic goals.

Patients taking sodium-glucose-co-transporter 2 inhibitors canagliflozin, dapagliflozin, and empagliflozin are at risk of dehydration and diabetic ketoacidosis, so they should temporarily stop taking these drugs should these symptoms occur.

Patients taking glucagon-like peptide-1 receptor agonists albiglutide, dulaglutide, exenatide-extended release, liraglutide, lixisenatide, and semaglutide are at risk of dehydration which can lead to a serious illness so they should adhere to strict fluid intake and a routine diet.

Dipeptidyl peptidase-4 inhibitors alogliptin, linagliptin, saxagliptin, and sitagliptin are generally well tolerated and can be continued.

“We do realize 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, and trial networks to provide evidence-based therapies are arising. Investigating subgroups with diabetes and how these relate to COVID-19 outcomes will be important, in particular investigating if some of the various management approaches would be particularly effective in managing diabetes in a COVID-19 context,” Bornstein et al. wrote.

For more information from the American Diabetes Association on COVID-19, visit the ADA’s COVID-19 hub (https://www.diabetes.org/coronavirus-covid-19) for vaccine plans by state.

Disclosures:

n/a

References

1. “American Diabetes Association Applauds CDC Decision to Prioritize All People with Diabetes for the COVID-19 Vaccine,” American Diabetes Association statement issued March 30, 2021 | Arlington, Virginia.

2. “COVID-19, People with Certain Medical Conditions,” Centers for Disease Control and Prevention, March 29, 2021.

3. “Underlying Medical Conditions Associated with High Risk for Severe COVID-19: Information for Healthcare Providers,” Centers for Disease Control and Prevention. Updated March 29, 2021. 

4. Ning Rosentha, MD, MPH, PhD; Zhun Cao, PhD; Jake Gundrum, MS; Jim Sianis, PharmD, MBA; Stella Safo, MD, MPH. “Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19,” JAMA Open Network. Dec. 10, 2020.  doi:10.1001/jamanetworkopen.2020.29058

5. “Science Brief: Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19,” Centers for Disease Control and Prevention. March 29, 2021.

6. Zeng-hong Wu, Yun Tang, and Qing Cheng. “Diabetes increases the mortality of patients with COVID-19: a meta-analysis,” Acta Diabetolgica, a publication of Springer Nature. Received: 23 April 2020 / Accepted: 6 May 2020. Published Feb. 2021. https://doi.org/10.1007/s00592-020-01546-0  

7. Rimesh Pal, Sanjay K Bhadada. “COVID-19 and diabetes mellitus: An unholy interaction of two pandemics,” Diabetes & Metabolic Syndrome:  Clinical Review & Reviews. May 6, 2020. DOI: 10.1016/j.dsx.2020.04.049

8. Stefan R Bornstein, Francesco Rubino, Kamlesh Khunti, et al. “Practical recommendations for the management of diabetes in patients with COVID-19,” The Lancet. Published in print June 2020. Published online April 23, 2020. https://doi.org/10.1016/S2213-8587(20)30152-2