Diabetes & COVID-19: Some Lessons Learned

COVID-19 vaccination is safe, effective, and especially important in people with diabetes due to the risk of more severe outcomes. While a session at ENDO 2022 emphasized the vaccine’s safety in this population, more research is needed as to whether the virus is a causal factor to an increase in new-onset type 1 diabetes cases. 

Get vaccinated and keep your blood sugar in tight control. That’s the best advice to give patients with diabetes to avoid the worst consequences of COVID-19 infection.

From the start of the pandemic, it was clear that people with diabetes and associated comorbidities need to be particularly vigilant about prevention because they are at increased risk of worse outcomes from COVID-19, including increased mortality. In the intervening time, researchers and clinicians have learned a great deal about the interplay between diabetes and COVID-19, and this new knowledge was the subject of a session at ENDO 2022 that took place both virtually and in-person in Atlanta in June.

Endocrine News interviewed two of the speakers to get the highlights: Ernesto Maddaloni, MD, PhD, is assistant professor of endocrinology and diabetes at Sapienza University in Rome, Italy. Francesco Vendrame, MD, PhD, is assistant professor of medicine in the division of endocrinology at the University of Miami in Florida.

Vaccination Safety

“There were a lot of questions about vaccination in people with diabetes,” Maddaloni says. “But we can say now that it is as safe as in people without diabetes. There is no increased risk of side effects and no [other additional] risk in people with diabetes. Vaccination is strongly suggested in people at high risk of complications, such as people with diabetes.”

Maddaloni says that several studies have suggested that diabetes patients can get the best results from vaccination by having their blood glucose levels under good control before and immediately after vaccination. “Having good metabolic control could help in having vaccination work better,” he says.

“Many studies have found that there was no general disruption in glucose control during the lockdown, including in measures such as hemoglobin A1c, time in range, and episodes of hypoglycemia.”

Vaccine side effects are similar in people with and without diabetes, with no evidence of a temporary worsening of glycemic control. Although a few cases of hyperglycemic emergencies have been reported, these are isolated, individual cases, and there is no proven cause-and-effect relationship between these episodes and vaccination. “The benefits are really much higher than the risks,” Maddaloni says.

A Fight for Control  

As in every aspect of diabetes, good glucose control is beneficial, and can even contribute to better outcomes when infected. COVID-19 infection is associated with hyperglycemia and increased insulin resistance even in patients without diabetes prior to infection.

There are several potential pathways by which the SARS-CoV-2 virus could disrupt glucose metabolism and downregulate the insulin-signaling pathway, according to Vendrame.

Early on, analysis of its molecular structure revealed that the SARS-CoV-2 virus has a spike protein on its surface that can bind to receptors on enzymes, such as angiotensin-converting enzyme 2 (ACE2), dipeptidyl peptidase-4 (DPP-4), and others, to gain entry into the beta cells of the pancreas. For example, ACE2 is an important enzyme for degrading angiotensin II. In downregulating ACE2, SARS-CoV-2 leads to more unopposed actions of angiotensin II, including more inflammatory activity.

The cytokine storm COVID-19 can induce can also downregulate the insulin-signaling pathway and immune cells activated by the virus can downregulate insulin receptors in skeletal muscle cells. Hospitalized patients are often treated with corticosteroids to quell the cytokine storm, and this treatment itself can contribute to hyperglycemia.

All these factors can lead to greater insulin resistance and hyperglycemia even in patients without diabetes prior to COVID-19 infection.

Viruses and Autoimmune Diseases

Researchers have raised concerns about COVID-19 being associated with an increase in new onset type 1 diabetes, Vendrame says. Viruses can trigger an autoimmune response, and there are several other autoimmune conditions that have been related to COVID-19 infection, including autoimmune thyroid disorders, Guillain-Barre syndrome, immune thrombocytopenic purpura, autoimmune hemolytic anemia, and Kawasaki disease.

Vendrame notes that a viral infection might trigger an autoimmune response through several possible mechanisms:

• In molecular mimicry, some viral antigens have a structure similar to self-antigens that cause a cross-reactive response, in which the immune system targets not only the virus, but also the patient’s own body.
• Bystander activation is a nonspecific, over-reactive immune response to a viral infection, in which self-antigens released from damaged tissue can stimulate autoreactive T cells in the vicinity, triggering autoimmunity.
• Epitope spreading is a related mechanism in a persistent viral infection, in which continued tissue damage triggers the release of more self-antigens and activation of additional autoreactive T cells.

Despite these various possible mechanisms of inducing autoimmunity, the question of whether COVID-19 has led to an increased number of cases of type 1 diabetes is unsettled. A meta-analysis published in the Journal of Medical Virology in July said that “the COVID‐19 pandemic has significantly increased the risk of global pediatric new‐onset type 1 diabetes” and that these cases seem to present with greater severity, including more diabetic ketoacidosis.

“There were a lot of questions about vaccination in people with diabetes. But we can say now that it is as safe as in people without diabetes. There is no increased risk of side effects and no [other additional] risk in people with diabetes. Vaccination is strongly suggested in people at high risk of complications, such as people with diabetes.”

Ernesto Maddaloni, MD, PhD, assistant professor, endocrinology and diabetes, Sapienza University in Rome, Italy

However, a study in Diabetes Care in September of the worldwide SWEET registry looked at new-onset type 1 diabetes in the context of the general worldwide increase in cases in recent years. It found that “the numbers of children with newly diagnosed type 1 diabetes increased significantly in the participating centers around the world in all age-groups over the past four years with an unchanged slope” during the COVID-19 pandemic. COVID-19 “gave the appearance of more cases by pushing up the regular seasonality of increased cases. The typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months.” 

“Longer follow-up studies are needed to address the change in type 1 diabetes incidence,” Vendrame says.

Success of Telemedicine

One of the big lessons from the pandemic came from the sudden tremendous increase in the use of telemedicine in response to the lockdowns, Vendrame says. This shift has been shown to be successful in terms of glucose control. Many studies have found that there was no general disruption in glucose control during the lockdown, including in measures such as hemoglobin A1c, time in range, and episodes of hypoglycemia.

Another important finding was that the use of technology such as glucose monitors and insulin pumps was associated with fewer adverse outcomes, including a lower incidence of patients presenting with diabetic ketoacidosis, Vendrame says.

Although at times it feels as if the COVID-19 pandemic has been happening for a long time, in terms of learning about a new virus, it has still been a short time frame. “This is an evolving area and new studies are published continuously,” Vendrame says.

Seaborg is a freelance writer based in Charlottesville, Va. His interview with Transatlantic Alliance Award recipient, Shlomo Melmed, MD, appeared in the September issue.