COVID-19 and Diabetes: Is There a Connection?

Diabetes, a chronic metabolic disease and an international health threat characterized by elevated blood glucose, is thought to be a risk factor for coronavirus disease 2019 (COVID-19).¹

The number of cases of diabetes has increased in the past 20 years and sparked higher costs for drugs and treatments.^1,2

In 2018, it was estimated that 34.2 million individuals of all ages in the United States, or about 10% of the population, had diabetes.³

The latest global estimate of individuals with diabetes was about 463 million in 2019, according to the International Diabetes Federation.¹

It is estimated that number will escalate to about 700 million by 2045.¹ Diabetes is triggered by a lack of insulin in type 1 diabetes and insulin resistance in type 2 diabetes.¹ Chronic hyperglycemia is the leading cause of metabolic imbalance in diabetes. It increases the risk of complications associated with diabetic ketoacidosis and hyperglycemic hyperosmolar states, for which remarkably high doses of insulin are warranted.¹

As of December 13, 2020, there have been more than 72 million cases of COVID-19 and more than 1.6 million deaths from the disease worldwide, according to Johns Hopkins University & Medicine.⁴

The magnitude of the threat of the coronavirus on the human body is still unknown. There is a lack of concrete evidence of the impact of the virus’ full invasion of the human body, and symptoms vary and present in different forms, including gastrointestinal and upper-respiratory symptoms.⁵ In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the proteins of the virus bind to receptors called angiotensinconverting enzyme 2, which are seen in key metabolic organs and tissues, including adipose tissue, the kidneys, pancreatic β cells, and the small intestine.⁶ Hence, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism, which could obscure the pathophysiology of preexisting diabetes.⁶ Numerous studies propose that substantial coagulation activation with severe COVID-19 infection is likely associated with inflammatory response secondary to cytokines release induced by viral invasion.⁷ The role of inflammation in diabetes is made based on the identification of inflammatory markers, such as adiponectin, C-reactive proteins, interleukin 6, leptin, plasminogen activator inhibitor-1, and tumor necrosis factor α.¹

Both COVID-19 and diabetes are associated with acute and chronic inflammation. In a research study conducted by Shang et al, laboratory data were analyzed and showed that individuals with diabetes had higher levels of C-reactive protein, neutrophils, and procalcitonin but a lower level of lymphocytes compared with individuals who didn’t have diabetes.⁸ The study’s radiologic data also showed a significantly higher incidence of bilateral pneumonia in patients with diabetes compared with individuals who did not have diabetes. These results showed that patients with COVID-19 and diabetes had more severe inflammatory responses and lung infiltration, which might contribute to the worse prognosis of SARS-CoV-2 infection.⁸ The relationship between diabetes and infection has been a pivotal concern.

In addition, numerous studies have indicated that diabetes is a risk factor in the morbidity and mortality of multiple viral infections, including influenza A (H1N1), Middle East respiratory syndrome, and SARS-CoV.⁸

A meta-analysis of 6 studies inclusive of 1527 patients with COVID-19 reported the prevalence of diabetes to be 9.7%.⁹ Among 1122 patients with COVID-19 who were admitted to the 88 US hospitals, the mortality rate was 4 times higher in those with known diabetes than those without known diabetes disease.¹⁰

The Figure¹⁰ shows that counterregulatory hormonal responses, the impairment of β-cell function with the inflammatory cytokine storm, and SARS-CoV-2 can precipitate further acute metabolic complications. Acute metabolic deterioration, hyperglycemia at admission, and new-onset diabetes, in turn, can worsen COVID-19 outcomes.¹⁰

Conclusion

It is well documented that diabetes causes an increased risk in the mortality and severity of COVID-19. However, the mechanism is not entirely clear. Understanding the relationship between COVID-19 and diabetes could advance therapeutic measures, but there is a scarcity of data on the matter.

Some studies have suggested that impaired immune systems make individuals with diabetes more susceptible to severe infections. High blood concentrations of inflammatory markers seen in patients with poorly controlled diabetes are linked to COVID-19 death and severity. Further randomized clinical trials are warranted to elucidate the clear mechanism between COVID-19 infection and diabetes.

GINA DUBE, PHARMD, RPH, CACP, is an advanced practice clinical pharmacist at Brigham and Women’s Hospital in Boston, Massachusetts.

REFERENCES

• Abdi A, Jalilian M, Sarbarzeh PA, Vlaisavljevic Z. Diabetes and COVID-19: a systemic review on the current evidences. Diabetes Res Clin Pract. 2020;166:108347. doi:10.1016/j.diabres.2020.108347
• Diabetes. World Health Organization. Accessed December 13, 2020. https://www.who.int/health-topics/diabetes#tab=tab_1
• National diabetes statistics report 2020. Centers for Disease Control and Prevention. Accessed December 5, 2020. https://www.cdc.gov/diabetes/ pdfs/data/statistics/national-diabetes-statistics-report.pdf
• COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins University & Medicine. Accessed December 13, 2020. https://coronavirus.jhu.edu/map.html
• COVID-19 protocols. Brigham and Women’s Hospital. Accessed December 6, 2020. https://covidprotocols.org/protocols/ clinical-course-and-epidemiology/#clinical-course
• Rubino F, Amiel SA, Zimmet P, et al. New-onset diabetes in COVID-19. N Engl J Med. 2020;383(8):789-790. doi:10.1056/NEJMc2018688
• Al-Ani F, Chehade S, Lazo-Langner A. Thrombosis risk associated with COVID-19 infection. a scoping review. Thromb Res. 2020;192:152-160. doi:10.1016/j.thromres.2020.05.039
• Shang J, Wang Q, Zhang H, et al. The relationship between diabetes mellitus and COVID-19 prognosis: a retrospective cohort study in Wuhan, China. Am J Med. 2021;134(1):e6-e14. doi:10.1016/j.amjmed.2020.05.033
• Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031
• Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8(9):782-792. doi:10.1016/S2213-8587(20)30238-2