Conclusion
Vaccines currently routinely recommended to the general population in the U.S.* do not cause diabetes.
Epidemiological Evidence
The 2012 report by the Institute of Medicine (IOM) 1, now called the National Academy of Medicine (NAM), described a number of studies with sufficient validity and precision that all reported a lack of an association between MMR, DTaP or Tdap vaccines and type 1 diabetes 2-7. Studies published since this report also reported a null, or in some cases even protective, association between vaccination and type 1 diabetes 8-14. This includes a meta-analysis of 23 observational studies investigating 16 different vaccines 15.
Studies examining inactivated seasonal influenza and Tdap vaccinations in pregnancy reported either no association with, or even a possible protective effect against, gestational diabetes 16-21. Retrospective cohort studies using the Vaccine Safety Datalink (VSD) published in 2018 and 2019 found no association between hepatitis A or B vaccination during pregnancy and gestational diabetes 22,23. National Health and Nutrition Examination Survey (NHANES) data from 2005-2010 suggested a possible protective effect of adult hepatitis B vaccination against diabetes 24,25. A 2016 retrospective observational study of California infants found no cases of type 1 diabetes during the 30-day risk interval after 46,486 doses of DTaP-IPV/Hib vaccine administered 26. A 2019 retrospective cohort study of northern California adolescents and young adults did not find an increased risk of type 1 diabetes following HPV vaccination 27. A 2017 South Korean nationwide cohort study found no associations between HPV vaccination and 33 predefined serious adverse events (including type 1 diabetes) 28. A 2020 systematic review and meta-analysis found no association between HPV vaccines and many autoimmune or other rare diseases (including type 1 diabetes) 29. Studies examining rotavirus vaccination reported either no association with, or even a possible protective effect against, diabetes 30-34. A 2021 VSD retrospective cohort study found no association between following the childhood vaccination schedule and type 1 diabetes 35. A 2021 Cochrane review determined that no evidence supports an association between MMR vaccination and type 1 diabetes 36.
Persons with chronic illnesses such as type 1 or type 2 diabetes have high morbidity and mortality associated with common infectious diseases such as influenza, hepatitis b, and pneumococcal disease. Thus, routine vaccination per current ACIP recommendations is also strongly recommended for all persons with diabetes by the American Diabetes Association 37,38. In addition, the ACIP recommends the administration of hepatitis b vaccine to all unvaccinated adults with diabetes mellitus aged 19 through 59 39.
Proposed Biological Mechanism
Mechanisms that may induce type 1 diabetes include activation of the complement system, in which a cascade of proteolysis and successive release of cytokines functions to amplify the immune response but can damage host cells if not properly regulated, as well as molecular mimicry, which refers to the possibility that similar epitopes shared between self-peptides and foreign peptides (introduced via infection or immunization) inadvertently cause the activation of autoreactive T or B cells, leading to autoimmunity. However, the IOM concluded that there was no mechanistic evidence for an association between vaccination and type 1 diabetes, as the publications reviewed provided no evidence beyond a temporal association 1.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
References
1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
2. DeStefano F, Mullooly JP, Okoro CA, Chen RT, Marcy SM, Ward JI, Vadheim CM, Black SB, Shinefield HR, Davis RL, Bohlke K. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics 2001; 108(6): E112.
3. Klein NP, Hansen J, Lewis E, Lyon L, Nguyen B, Black S, Weston WM, Wu S, Li P, Howe B, Friedland LR. Post-marketing safety evaluation of a tetanus toxoid, reduced diphtheria toxoid and 3-component acellular pertussis vaccine administered to a cohort of adolescents in a United States health maintenance organization. The Pediatric infectious disease journal 2010; 29(7): 613-7.
4. Altobelli E, Petrocelli R, Verrotti A, Valenti M. Infections and risk of type I diabetes in childhood: a population-based case-control study. Eur J Epidemiol 2003; 18(5): 425-30.
5. Blom L, Nystrom L, Dahlquist G. The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood. Diabetologia 1991; 34(3): 176-81.
6. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Childhood vaccination and type 1 diabetes. The New England journal of medicine 2004; 350(14): 1398-404.
7. Patterson CC. Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. EURODIAB Substudy 2 Study Group. Diabetologia 2000; 43(1): 47-53.
8. Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw KL, Jacobsen SJ. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271(2): 193-203.
9. Duderstadt SK, Rose CE, Jr., Real TM, Sabatier JF, Stewart B, Ma G, Yerubandi UD, Eick AA, Tokars JI, McNeil MM. Vaccination and risk of type 1 diabetes mellitus in active component U.S. Military, 2002-2008. Vaccine 2012; 30(4): 813-9.
10. Hummel M, Fuchtenbusch M, Schenker M, Ziegler AG. No major association of breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB Study. Diabetes Care 2000; 23(7): 969-74.
11. Black SB, Lewis E, Shinefield HR, Fireman B, Ray P, DeStefano F, Chen R. Lack of association between receipt of conjugate haemophilus influenzae type B vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort. The Pediatric infectious disease journal 2002; 21(6): 568-9.
12. Karvonen M, Cepaitis Z, Tuomilehto J. Association between type 1 diabetes and Haemophilus influenzae type b vaccination: birth cohort study. BMJ 1999; 318(7192): 1169-72.
13. Elding Larsson H, Lynch KF, Lonnrot M, Haller MJ, Lernmark A, Hagopian WA, She JX, Simell O, Toppari J, Ziegler AG, Akolkar B, Krischer JP, Rewers MJ, Hyoty H. Pandemrix(R) vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children. Diabetologia 2018; 61(1): 193-202.
14. Vaarala O, Jokinen J, Lahdenkari M, Leino T. Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life. The Pediatric infectious disease journal 2017; 36(7): 674-5.
15. Morgan E, Halliday SR, Campbell GR, Cardwell CR, Patterson CC. Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia 2016; 59(2): 237-43.
16. Kharbanda EO, Vazquez-Benitez G, Lipkind H, Naleway A, Lee G, Nordin JD. Inactivated influenza vaccine during pregnancy and risks for adverse obstetric events. Obstet Gynecol 2013; 122(3): 659-67.
17. Naleway AL, Irving SA, Henninger ML, Li DK, Shifflett P, Ball S, Williams JL, Cragan J, Gee J, Thompson MG. Safety of influenza vaccination during pregnancy: a review of subsequent maternal obstetric events and findings from two recent cohort studies. Vaccine 2014; 32(26): 3122-7.
18. Fabiani M, Bella A, Rota MC, Clagnan E, Gallo T, D’Amato M, Pezzotti P, Ferrara L, Demicheli V, Martinelli D, Prato R, Rizzo C. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy. Vaccine 2015; 33(19): 2240-7.
19. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway AL, Lee GM, Hambidge S, Jackson ML, Omer SB, McCarthy N, Nordin JD. Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007-2013. Vaccine 2016; 34(7): 968-73.
20. Sancovski M, Mesaros N, Feng Y, Ceregido MA, Luyts D, De Barros E. Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study. Human vaccines & immunotherapeutics 2019; 15(12): 2873-81.
21. Griffin JB, Yu L, Watson D, Turner N, Walls T, Howe AS, Jiang Y, Petousis-Harris H. Pertussis Immunisation in Pregnancy Safety (PIPS) Study: A retrospective cohort study of safety outcomes in pregnant women vaccinated with Tdap vaccine. Vaccine 2018; 36(34): 5173-9.
22. Groom HC, Irving SA, Koppolu P, Smith N, Vazquez-Benitez G, Kharbanda EO, Daley MF, Donahue JG, Getahun D, Jackson LA, Tse Kawai A, Klein NP, McCarthy NL, Nordin JD, Sukumaran L, Naleway AL. Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety Datalink study. Vaccine 2018; 36(41): 6111-6.
23. Groom HC, Smith N, Irving SA, Koppolu P, Vazquez-Benitez G, Kharbanda EO, Daley MF, Donahue JG, Getahun D, Jackson LA, Klein NP, McCarthy NL, Nordin JD, Panagiotakopoulos L, Naleway AL. Uptake and safety of hepatitis A vaccination during pregnancy: A Vaccine Safety Datalink study. Vaccine 2019; 37(44): 6648-55.
24. Karnchanasorn R, Ou HY, Lin J, Chuang LM, Chiu KC. Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination. Current diabetes reports 2016; 16(10): 101.
25. Huang J, Ou HY, Lin J, Karnchanasorn R, Feng W, Samoa R, Chuang LM, Chiu KC. The Impact of Hepatitis B Vaccination Status on the Risk of Diabetes, Implicating Diabetes Risk Reduction by Successful Vaccination. PloS one 2015; 10(10): e0139730.
26. Hansen J, Timbol J, Lewis N, Pool V, Decker MD, Greenberg DP, Klein NP. Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers. Vaccine 2016; 34(35): 4172-9.
27. Klein NP, Goddard K, Lewis E, Ross P, Gee J, DeStefano F, Baxter R. Long term risk of developing type 1 diabetes after HPV vaccination in males and females. Vaccine 2019; 37(14): 1938-44.
28. Yoon D, Lee JH, Lee H, Shin JY. Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study. BMJ (Clinical research ed) 2021; 372: m4931.
29. Willame C, Gadroen K, Bramer W, Weibel D, Sturkenboom M. Systematic Review and Meta-analysis of Postlicensure Observational Studies on Human Papillomavirus Vaccination and Autoimmune and Other Rare Adverse Events. The Pediatric infectious disease journal 2020; 39(4): 287-93.
30. Hemming-Harlo M, Lähdeaho ML, Mäki M, Vesikari T. Rotavirus Vaccination Does Not Increase Type 1 Diabetes and May Decrease Celiac Disease in Children and Adolescents. The Pediatric infectious disease journal 2019; 38(5): 539-41.
31. Rogers MAM, Basu T, Kim C. Lower Incidence Rate of Type 1 Diabetes after Receipt of the Rotavirus Vaccine in the United States, 2001-2017. Scientific reports 2019; 9(1): 7727.
32. Burke RM, Tate JE, Dahl RM, Saydah S, Imperatore G, Gregg EW, Parashar UD. Rotavirus Vaccination and Type 1 Diabetes Risk Among US Children With Commercial Insurance. JAMA pediatrics 2020; 174(4): 383-5.
33. Glanz JM, Clarke CL, Xu S, Daley MF, Shoup JA, Schroeder EB, Lewin BJ, McClure DL, Kharbanda E, Klein NP, DeStefano F. Association Between Rotavirus Vaccination and Type 1 Diabetes in Children. JAMA pediatrics 2020; 174(5): 455-62.
34. Inns T, Fleming KM, Iturriza-Gomara M, Hungerford D. Paediatric rotavirus vaccination, coeliac disease and type 1 diabetes in children: a population-based cohort study. BMC medicine 2021; 19(1): 147.
35. Glanz JM, Clarke CL, Daley MF, Shoup JA, Hambidge SJ, Williams JTB, Groom HC, Kharbanda EO, Klein NP, Jackson LA, Lewin BJ, McClure DL, Xu S, DeStefano F. The Childhood Vaccination Schedule and the Lack of Association With Type 1 Diabetes. Pediatrics 2021; 148(6).
36. Di Pietrantonj C, Rivetti A, Marchione P, Debalini MG, Demicheli V. Vaccines for measles, mumps, rubella, and varicella in children. The Cochrane database of systematic reviews 2021; 11(11): Cd004407.
37. Vaccination Practices for Hepatitis B, Influenza, and Pneumococcal Disease for People With Diabetes. The Diabetes Educator 2014; 40(1): 122-4.
38. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clinical diabetes : a publication of the American Diabetes Association 2016; 34(1): 3-21.
39. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbidity and mortality weekly report 2011; 60(50): 1709-11.
