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Effects of diabetes mellitus regulation on antibody response to inactivated virus vaccine: a systematic review

  • Dewi Prasetyaningtyas ,
  • Gatot Soegiarto ,
  • Laksmi Wulandari ,


Background: Diabetes mellitus (DM) could hamper the immune responses, including that induced by the vaccine. The aim of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19-19) inactivated vaccines in patients with DM either controlled or uncontrolled through a systematic review approach.

Methods: Without regard to time constraints, searches were conducted in ProQuest, Embase, and PubMed  to assess the available data on the impact of DM regulation on the immunogenicity of post-vaccinated DM patients. The PRISMA guideline and the PICO criteria were used. The quality of studies was assessed using the National Institutes of Health (NIH) quality assessment tool. There is not enough Available data comparing the immunogenicity of the vaccine in controlled and uncontrolled DM patients is limited.

Results: Out of 20,657 articles, five studies were included, of which three had good quality and two had fair quality. Our data suggested that DM patients vaccinated with CoronaVac/SinoVac had lower seroconversion rates significantly lower compared to non-DM patients. The immunogenicity of BBV-152 vaccine in DM patients was also significantly lower than in patients without DM. Studies comparing the immunogenicity of the vaccine between controlled and uncontrolled DM patients are limited.

Conclusion: Patients with DM have lower antibody levels than non-DM patients who received inactivated COVID-19 patients. Glycemic management has emerged as critical to maximizing the immunogenicity induced by inactivated vaccines in a small number of patients; however, to support this conclusion, studies with adequate number of patients are critical.


  1. Soegiarto G, Purnomosari D, Wulandari L, Mahdi BA, Fahmita KD, Hadmoko ST, et al. Incidence of SARS-CoV-2 infection in hospital workers before and after vaccination programme in East Java, Indonesia-A retrospective cohort study. Lancet Reg Heal Southeast Asia. 2022/12/12. 2023;10:100130. Available from:
  2. Mutiawati E, Kusuma HI, Fathima R, Syahrul S, Musadir N. A comparison study of headache characteristics and headache-associated quality-of-life of COVID-19 and non-COVID-19 patients. Narra J. 2022;2(3):e93. Available from:
  3. Nadzifah YN, Hidajah AC. The Relationship of Diabetes Mellitus And Hypertension With Mortality In Covid-19 Patients. J Berk Epidemiol. 2022;10(2):219–26. Available from:
  4. Ernawati T, Nugroho N, Novita BD, Tahalele PL, Suwasanti N, Darmadi ET, et al. Covid-19 Patients’ Characteristic In Covid-19 Referral Hospital, Surabaya, Indonesia. J Berk Epidemiol. 2022;10(1):48. Available from:
  5. Lim S, Bae JH, Kwon H-S, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2020/11/13. 2021;17(1):11–30. Available from:
  6. Sharun K, Tiwari R, Yatoo MI, Natesan S, Megawati D, Singh KP, et al. A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19. Narra J. 2022;2(3):e92. Available from:
  7. Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021/02/03. 2021;21(6):803–12. Available from:
  8. Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomized, phase 1 trial. Lancet Infect Dis. 2021/01/21. 2021;21(5):637–46. Available from:
  9. Clemens SC, Folegatti P, Emary K, Weckx L, Ratcliff J, Bibi S, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil; an exploratory analysis of a randomized controlled trial [Internet]. Research Square Platform LLC; 2021. Available from:
  10. Jones I, Roy P. Sputnik V COVID-19 vaccine candidate appears safe and effective. Lancet (London, England). 2021/02/02. 2021;397(10275):642–3. Available from:
  11. Logunov DY, Dolzhikova I V, Shcheblyakov D V, Tukhvatulin AI, Zubkova O V, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet (London, England). 2021/02/02. 2021;397(10275):671–81. Available from:
  12. Bruxvoort KJ, Sy LS, Qian L, Ackerson BK, Luo Y, Lee GS, et al. Real-world effectiveness of the mRNA-1273 vaccine against COVID-19: Interim results from a prospective observational cohort study. Lancet Reg Heal Am. 2021/11/25. 2022;6:100134. Available from:
  13. Boroumand AB, Forouhi M, Karimi F, Moghadam AS, Naeini LG, Kokabian P, et al. Immunogenicity of COVID-19 vaccines in patients with diabetes mellitus: A systematic review. Front Immunol. 2022;13:940357. Available from:
  14. American Diabetes Association. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2020. Diabetes Care. 2019;43(Supplement_1):S14–31. Available from:
  15. Guzmán-Martínez O, Guardado K, de Guevara EL, Navarro S, Hernández C, Zenteno-Cuevas R, et al. IgG Antibodies Generation and Side Effects Caused by Ad5-nCoV Vaccine (CanSino Biologics) and BNT162b2 Vaccine (Pfizer/BioNTech) among Mexican Population. Vaccines. 2021;9(9):999. Available from:
  16. Alqassieh R, Suleiman A, Abu-Halaweh S, Santarisi A, Shatnawi O, Shdaifat L, et al. Pfizer-BioNTech and Sinopharm: A Comparative Study on Post-Vaccination Antibody Titers. Vaccines. 2021;9(11):1223. Available from:
  17. Güzel EÇ, Çelikkol A, Erdal B, Sedef N. Immunogenicity after CoronaVac vaccination. Rev Assoc Med Bras. 2021;67(10):1403–8. Available from:
  18. Sauré D, O’Ryan M, Torres JP, Zuniga M, Santelices E, Basso LJ. Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study. Lancet Infect Dis. 2021/09/09. 2022;22(1):56–63. Available from:
  19. Singh AK, Phatak SR, Singh R, Bhattacharjee K, Singh NK, Gupta A, et al. Antibody response after first and second-dose of ChAdOx1-nCOV (Covishield(TM)®) and BBV-152 (Covaxin(TM)®) among health care workers in India: The final results of cross-sectional coronavirus vaccine-induced antibody titre (COVAT) study. Vaccine. 2021/09/24. 2021;39(44):6492–509. Available from:
  20. Karamese M, Tutuncu EE. The effectiveness of inactivated SARS-CoV-2 vaccine (CoronaVac) on antibody response in participants aged 65 years and older. J Med Virol. 2021/08/31. 2022;94(1):173–7. Available from:
  21. Yuan P, Ai P, Liu Y, Ai Z, Wang Y, Cao W, et al. Safety, Tolerability, and Immunogenicity of COVID-19 Vaccines: A Systematic Review and Meta-Analysis. medRxiv Prepr Serv Heal Sci. 2020;2020.11.03.20224998. Available from:
  22. Lumley SF, O’Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med. 2020/12/23. 2021;384(6):533–40. Available from:
  23. Wan EYF, Wang Y, Chui CSL, Mok AHY, Xu W, Yan VKC, et al. Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series. lancet Heal Longev. 2022/07/04. 2022;3(7):e491–500. Available from:
  24. Grenfell RFQ, Almeida NBF, Filgueiras PS, Corsini CA, Gomes SVC, de Miranda DAP, et al. Immunogenicity, Effectiveness, and Safety of Inactivated Virus (CoronaVac) Vaccine in a Two-Dose Primary Protocol and BNT162b2 Heterologous Booster in Brazil (Immunita-001): A One Year Period Follow Up Phase 4 Study. Front Immunol. 2022;13:918896. Available from:
  25. Teijaro JR, Farber DL. COVID-19 vaccines: modes of immune activation and future challenges. Nat Rev Immunol. 2021;21(4):195–7. Available from:
  26. Fendler A, de Vries EGE, GeurtsvanKessel CH, Haanen JB, Wörmann B, Turajlic S, et al. COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety. Nat Rev Clin Oncol. 2022/03/11. 2022;19(6):385–401. Available from:
  27. Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020/06/18. 2020;584(7821):437–42. Available from:
  28. Bintoro SUY, Dwijayanti NMI, Pramudya D, Amrita PN, Romadhon PZ, Asmarawati TP, et al. Hematologic and coagulopathy parameter as a survival predictor among moderate to severe COVID-19 patients in non- ICU ward: a single-center study at the main referral hospital in Surabaya, East Java, Indonesia. F1000Research. 2021;10:791. Available from:
  29. Dal Lin C, Tona F, Osto E. The crosstalk between the cardiovascular and the immune system. Vasc Biol (Bristol, England). 2019;1(1):H83–8. Available from:
  30. Yu Y, Esposito D, Kang Z, Lu J, Remaley AT, De Giorgi V, et al. mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 and its high affinity variants. Sci Rep. 2022;12(1):2628. Available from:
  31. Marfella R, D’Onofrio N, Sardu C, Scisciola L, Maggi P, Coppola N, et al. Does poor glycaemic control affect the immunogenicity of the COVID-19 vaccination in patients with type 2 diabetes: The CAVEAT study. Diabetes Obes Metab. 2021/10/01. 2022;24(1):160–5. Available from:
  32. Sourij C, Tripolt NJ, Aziz F, Aberer F, Forstner P, Obermayer AM, et al. Humoral immune response to COVID-19 vaccination in diabetes is age-dependent but independent of type of diabetes and glycaemic control: The prospective COVAC-DM cohort study. Diabetes Obes Metab. 2022/01/24. 2022;24(5):849–58. Available from:
  33. Wafa IA, Pratama NR, Sofia NF, Anastasia ES, Konstantin T, Wijaya MA, et al. Impact of COVID-19 Lockdown on the Metabolic Control Parameters in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis. Diabetes Metab J. 2022/03/08. 2022;46(2):260–72. Available from:
  34. Mudatsir M, Fajar JK, Wulandari L, Soegiarto G, Ilmawan M, Purnamasari Y, et al. Predictors of COVID-19 severity: a systematic review and meta-analysis. F1000Research. 2020;9:1107. Available from:
  35. Wardhani SO, Fajar JK, Nurarifah N, Hermanto DH, Fatonah S, Djajalaksana S, et al. The predictors of high titer of anti-SARS-CoV-2 antibody of convalescent plasma donors. Clin Epidemiol Glob Heal. 2021/05/10. 2021;11:100763. Available from:
  36. Pozzilli P, Gale EA, Visalli N, Baroni M, Crovari P, Frighi V, Cavallo MG, Andreani D. The immune response to influenza vaccination in diabetic patients. Diabetologia. 1986;29(12):850-4. Available from: doi: 10.1007/BF00870139.
  37. Artha IMJR, Bhargah A, Dharmawan NK, Pande UW, Triyana KA, Mahariski PA, Yuwono J, Bhargah V, Prabawa IPY, Manuaba IBAP, Rina IK. High level of individual lipid profile and lipid ratio as a predictive marker of poor glycemic control in type-2 diabetes mellitus. Vasc Health Risk Manag. 2019 Jun 5;15:149-157. Available from: doi: 10.2147/VHRM.S209830.
  38. Kshanti IA, Aji G, Epriliawati M, Mokoagow MI, Nasarudin J, Magfira N, Sari AP, Manurung A, Djojo AY, Wardoyo EY, Iskandar M, Darnindro N, Mardiyah R. Clinical presentation and outcome of COVID-19 infection in Type 2 Diabetes Mellitus: a preliminary data from a tertiary hospital in Jakarta during the early days of the pandemic. Bali Med J. 2020;9(3):787-93. Available from:

How to Cite

Prasetyaningtyas, D., Soegiarto, G. ., & Wulandari, L. . (2023). Effects of diabetes mellitus regulation on antibody response to inactivated virus vaccine: a systematic review. Bali Medical Journal, 12(2), 1478–1483.




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Dewi Prasetyaningtyas
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Gatot Soegiarto
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Laksmi Wulandari
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