The Dual Burden of Type 1 Diabetes and COVID-19
Authors: Justin M. Gregory, Daniel J. Moore
Journal: Annals of Internal Medicine (2021)

Ideas and Opinions26 January 2021The Dual Burden of Type 1 Diabetes and COVID-19FREEJustin M. Gregory, MD and Daniel J. Moore, MD, PhDJustin M. Gregory, MDVanderbilt University School of Medicine, Nashville, Tennessee (J.M.G., D.J.M.).Search for more papers by this author and Daniel J. Moore, MD, PhDVanderbilt University School of Medicine, Nashville, Tennessee (J.M.G., D.J.M.).Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0367 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the year after the first case of coronavirus disease 2019 (COVID-19) was identified in the United States on 21 January 2020, the nation's death toll from the virus has passed 400 000, a number on par with U.S. fatalities in World War II (405 399) (1). From as early as February 2020, data from China indicated that the COVID-19 case-fatality rate was 3 times higher in patients with diabetes than in those without it (2). As the pandemic spread beyond China, mounting evidence showed that, although individuals with diabetes were no more prone to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the overall population, they made up a disproportionately higher percentage of severe COVID-19 cases (3). These early analyses largely did not distinguish between types of diabetes. Yet, because of its higher worldwide prevalence, these data likely largely reflected the experience of patients with type 2 diabetes mellitus (T2DM). This early lack of data on patients with type 1 diabetes mellitus (T1DM) may have influenced the Centers for Disease Control and Prevention's (CDC) current guidance, which states that adult patients with T2DM “are at increased risk” for severe illness from COVID-19, whereas those with T1DM “might be at an increased risk” for severe illness (4). How should physicians extrapolate what we know about SARS-CoV-2 and T2DM to patients with T1DM?Fortunately, by the second half of 2020, data emerged quantifying COVID-19–related morbidity and mortality in patients with T1DM (5–8). These analyses showed that patients with T1DM experienced markedly higher adjusted odds of hospitalization (6), severity of illness (6, 8), and death (5, 8) than patients who did not have T1DM (Table). In conflict with present CDC guidance, these data further demonstrate that, when compared with individuals without diabetes, people with T1DM have similar to slightly higher adjusted risk for adverse COVID-19 outcomes than people with T2DM. Notably, we have found that patients with COVID-19 and well-controlled T1DM have 3-fold higher unadjusted odds for hospitalization than those who do not have diabetes. This evidence indicates that COVID-19 presents an elevated threat to those living with T1DM.Table. Adjusted Odds Ratios for Adverse COVID-19 Outcomes in Patients With T1DM and T2DMIn addition to quantifying the excess risk for poor COVID-19 outcomes in T1DM, recent studies shed light on patient subgroups that are particularly vulnerable. For example, a population-wide analysis of 264 390 patients with T1DM found that the adjusted hazard ratio for COVID-19–related death for Black versus White patients was 1.77 (95% CI, 1.25 to 2.49) (7). When patients in the most deprived quintile of the deprivation index were compared with those in the least deprived quintile, the adjusted hazard ratio was 1.93 (CI, 1.36 to 2.72). By comparison, when the investigators analyzed the association of mortality and glycemic control, the only statistically significant association was among patients with hemoglobin A1c levels greater than 10.0% compared with those with levels of 6.5% to 7% (adjusted hazard ratio, 2.23 [CI, 1.50 to 3.30]). Collectively, available evidence suggests that even if patients with T1DM could continually optimize glycemia and societal health inequities could be rectified, these individuals would remain at increased risk for poor outcomes from COVID-19 compared with people without diabetes.In December 2020, Pfizer-BioNTech (9) and Moderna (10) reported safety and efficacy data from placebo-controlled randomized clinical trials of their COVID-19 vaccines to the U.S. Food and Drug Administration. The effectiveness of the vaccines in preventing confirmed COVID-19 were 95.0% (CI, 90.3% to 97.6%) and 94.5% (CI, 86.5% to 97.8%), respectively. Moreover, severe COVID-19 occurred only once among vaccinated participants. Of importance, efficacy findings were consistent across nearly every subgroup analyzed, including racial and ethnic minorities, participants older than 65 years, and participants with a high-risk condition. People with diabetes comprised 8.4% and 9.4% of each trial's participants (although neither report identified types of diabetes) and derived 94.7% (CI, 66.8% to 99.9%) and 100% efficacy from each vaccine, respectively. Thus, the vaccines were not only profoundly protective against COVID-19, they were equally effective in preventing the virus in participants with and without diabetes.In 1848, Horace Mann, the first great American advocate for public education, famously wrote, “Education then, beyond all other devices of human origin, is a great equalizer of the conditions of men—the balance wheel of the social machinery.” At this critical moment in our history, we believe a new great equalizer has come to the fore: the COVID-19 vaccine. The existing evidence clearly shows that the vaccine presents a golden opportunity to rectify health inequities experienced by people with T1DM. Although these individuals have a markedly higher risk for severe COVID-19—and higher still for those who are also socially disadvantaged—we now possess an effective tool to mitigate this risk. Presently, individual states are on the threshold of vaccinating persons with high-risk medical conditions, and many do not include T1DM in this category. This shortcoming needs prompt remediation to prevent further excessive morbidity and mortality in the T1DM population.By prioritizing patients with T1DM, states will maximize the vaccine's benefit by decreasing the excess individual burden of severe illness and reducing hospitalizations that strain health care systems. Further, this prioritization will mitigate health inequities that are demonstrably present among disadvantaged subgroups of patients with T1DM. In light of these considerations, we urge the Advisory Committee on Immunization Practices to identify the more than 1.6 million Americans who live with T1DM as individuals at increased risk for poor COVID-19 outcomes.References1. U.S. Department of Veterans Affairs. Fact Sheet: America's Wars. November 2020. Accessed at www.va.gov/opa/publications/factsheets/fs_americas_wars.pdf on 19 January 2021. Google Scholar2. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239-1242. [PMID: 32091533] doi:10.1001/jama.2020.2648 CrossrefMedlineGoogle Scholar3. Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8:782-792. [PMID: 32687793] doi:10.1016/S2213-8587(20)30238-2 CrossrefMedlineGoogle Scholar4. Centers for Disease Control and Prevention. COVID-19: People with Certain Medical Conditions. Updated 29 December 2020. Accessed at www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html on 19 January 2021. Google Scholar5. Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8:813-822. [PMID: 32798472] doi:10.1016/S2213-8587(20)30272-2 CrossrefMedlineGoogle Scholar6. Gregory JM, Slaughter JC, Duffus SH, et al. COVID-19 severity is tripled in the diabetes community: a prospective analysis of the pandemic's impact in type 1 and type 2 diabetes. Diabetes Care. 2021;44:526-532. [PMID: 33268335] doi:10.2337/dc20-2260 CrossrefMedlineGoogle Scholar7. Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2020;8:823-833. [PMID: 32798471] doi:10.1016/S2213-8587(20)30271-0 CrossrefMedlineGoogle Scholar8. McGurnaghan SJ, Weir A, Bishop J, et al; Public Health Scotland COVID-19 Health Protection Study Group. Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland. Lancet Diabetes Endocrinol. 2021;9:82-93. [PMID: 33357491] doi:10.1016/S2213-8587(20)30405-8 CrossrefMedlineGoogle Scholar9. Vaccines and Related Biological Products Advisory Committee Meeting, FDA Briefing Document: Pfizer-BioNTech COVID-19 Vaccine. U.S. Food and Drug Administration; 10 December 2020. Accessed at www.fda.gov/media/144245/download on 8 January 2021. Google Scholar10. Vaccines and Related Biological Products Advisory Committee Meeting, FDA Briefing Document: Moderna COVID-19 Vaccine. U.S. Food and Drug Administration; 17 December 2020. Accessed at www.fda.gov/media/144434/download on 8 January 2021. Google Scholar Comments 0 Comments Sign In to Submit A Comment Shanika Nanayakkara, Kouji H. HaradaThe University of Sydney, Kyoto University29 January 2021 Can we wait for consistent evidence? We agree with the opinion by Gregory and Moore (1). Evidence from several recent studies demonstrate that patients with type 1 diabetes (T1DM) do have the same risk for COVID-19 as patients with type 2 diabetes mellitus (T2DM). This observation and the potential effectiveness of COVID-19 vaccine justify equal prioritization for T1DM to phase 1c. The advisory committee on immunization practices ranked patients with type 2 diabetes as "at high risk" for more serious illnesses in COVID-19 based on the body of evidence available at the time of recommendation. It was reported that T1DM patients might be at risk of serious illness, but the data were judged to be "limited evidence" (2). Why were T1DM prioritized differently? One explanation is that the recent evidence demonstrating serious illness from COVID-19 in T1DM was not available for consideration when developing the recommendations. Undoubtedly, there is a substantial difference in the volume of evidence on clinical outcomes of COVID-19 available for T1DM and T2DM populations which may be due to the differences in prevalence of the two conditions. But, is it ethical to wait until sufficient evidence is available to develop recommendations? Or is it ethical to develop recommendations ignoring the fact that the volume of evidence is not consistent across different disease populations? We strongly believe that the decision on COVID-19 vaccine prioritization need to be made with consideration of the inequalities in evidence base to prevent minor patient populations from being disadvantaged. In addition, pathophysiological knowledge may complement the gap between these two types of diabetes (3). Introducing additional phases between phase 1c and phase 2 can also be considered to cover potentially at high risk patient populations with “limited evidence”. (1) Justin M. Gregory, Daniel J. Moore. The Dual Burden of Type 1 Diabetes and COVID-19. Ann Intern Med. [Epub ahead of print 26 January 2021]. doi:10.7326/M21-0367 (2) CDC, Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19. Updated Nov. 2, 2020 https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/evidence-table.html (3) Lim S, Bae JH, Kwon HS et al. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol 17, 11–30, 2021. Author, Article, and Disclosure InformationAuthors: Justin M. Gregory, MD; Daniel J. Moore, MD, PhDAffiliations: Vanderbilt University School of Medicine, Nashville, Tennessee (J.M.G., D.J.M.).Financial Support: Drs. Gregory and Moore are supported by the Department of Pediatrics of Vanderbilt University Medical Center. Dr. Gregory acknowledges support from career development awards from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (K23DK123392) and JDRF (5-ECR-2020-950-A-N). The content is solely the responsibility of the authors and does not necessarily represent the official views of Vanderbilt University Medical Center, the National Institutes of Health, or the JDRF.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-0367.Corresponding Author: Justin M. Gregory, MD, Division of Pediatric Endocrinology, 1500 21st Avenue, Suite 1514, Nashville, TN 37232; e-mail, justin.m.gregory.1@vumc.org.Current Author Addresses: Drs. Gregory and Moore: Division of Pediatric Endocrinology, 1500 21st Avenue, Suite 1514, Nashville, TN 37232.Author Contributions: Conception and design: J.M. Gregory, D.J. Moore.Analysis and interpretation of the data: J.M. Gregory, D.J. Moore.Drafting of the article: J.M. Gregory, D.J. Moore.Critical revision for important intellectual content: J.M. Gregory, D.J. Moore.Final approval of the article: J.M. Gregory, D.J. Moore.Provision of study materials or patients: J.M. Gregory.Statistical expertise: J.M. Gregory.Collection and assembly of data: J.M. Gregory.This article was published at Annals.org on 26 January 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffect of COVID-19 vaccine on blood glucose metrics in Arabic people with type 1 diabetesSevere COVID-19 Infection in Type 1 and Type 2 Diabetes During the First Three Waves in SwedenExternal Validation of Mortality Scores among High-Risk COVID-19 Patients: A Romanian Retrospective Study in the First Pandemic YearCOVID-19 Exacerbates Insulin Resistance During Diabetic Ketoacidosis in Pediatric Patients With Type 1 DiabetesBNT162b2 mRNA COVID-19 Vaccine Does Not Impact the Honeymoon Phase in Type 1 Diabetes: A Case ReportClinical Significance of COVID-19 and Diabetes: In the Pandemic Situation of SARS-CoV-2 Variants Including Omicron (B.1.1.529)COVID-19 and Diabetes: Understanding the Interrelationship and Risks for a Severe Course May 2021Volume 174, Issue 5 Page: 703-704 Keywords COVID-19 Endocrinology Hazard ratio Hospitalizations Morbidity Mortality Pediatrics Type 1 diabetes Type 2 diabetes Vaccines ePublished: 26 January 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. 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