Diabetologia

, Volume 36, Issue 12, pp 1303–1308 | Cite as

Decline of mumps antibodies in Type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of Type 1 diabetes after introduction of the mumps-measles-rubella vaccine in Finland

  • H. Hyöty
  • M. Hiltunen
  • A. Reunanen
  • P. Leinikki
  • T. Vesikari
  • R. Lounamaa
  • J. Tuomilehto
  • H. K. Åkerblom
  • the Childhoood Diabetes in Finland Study Group
  • L. Toivanen
  • E. A. Kaprio
  • A. Fagerlund
  • M. Flittner
  • B. Gustafsson
  • C. Häggqvist
  • A. Hakulinen
  • L. Herva
  • P. Hiltunen
  • T. Huhtamäki
  • N. -P. Huttunen
  • T. Huupponen
  • M. Hyttinen
  • T. Joki
  • R. Jokisalo
  • M. -L. Käär
  • S. Kallio
  • U. Kaski
  • M. Knip
  • L. Laine
  • J. Lappalainen
  • J. Mäenpää
  • A. -L. Mäkelä
  • K. Niemi
  • A. Niiranen
  • A. Nuuja
  • P. Ojajärvi
  • T. Otonkoski
  • K. Pihlajamäki
  • S. Pöntynen
  • J. Rajantie
  • J. Sankala
  • J. Schumacher
  • M. Sillanpää
  • M. -R. Ståhlberg
  • C. -H. Stråhlmann
  • T. Uotila
  • M. Väre
  • P. Varimo
  • G. Wettenstrand
Originals

Summary

A nationwide mumps-measles-rubella vaccination was introduced in 1982 in Finland to children aged 1.5 to 6 years and since then mumps has virtually disappeared in the country. We investigated whether this rapid epidemiological change had any impact on antibody activity against mumps virus in Type 1 (insulin-dependent) diabetic children or on the incidence of Type 1 diabetes in Finland. Two case-control series were collected before (series I and II) and three series after (series III–V) the introduction of the vaccination. IgA class mumps antibody levels were significantly higher in Type 1 diabetic children than in matched control children in the first two but not in the three later series. IgG class antibody levels were similar in patients and control subjects in the first two series but significantly lower in patients than in control subjects in the three later series. The overall incidence of Type 1 diabetes in 0–14-year-old children increased until 1987 but remained about the same during 1988–1990. In 5–9-year-old children no further increase in Type 1 diabetes was seen since 1985, whereas in 0–4-year-old children the incidence continued to rise until 1990. The results suggest that the elimination of natural mumps by mumps-measles-rubella vaccination may have decreased the risk for Type 1 diabetes in Finland; a possible causal relationship is substantiated by the observed concomitant decrease in mumps antibody levels in diabetic children. However, further studies are required to determine if the vaccine virus, like natural mumps, could trigger the clinical onset of Type 1 diabetes in young children.

Key words

Mumps mumps antibodies mumps-measlesrubella vaccination Type 1 (insulin-dependent) diabetes mellitus 

References

  1. 1.
    Gundersen E (1924) Is diabetes of infectious origin? J Infect Dis 41: 197–202Google Scholar
  2. 2.
    Melin K, Ursing B (1958) Diabetes mellitus as complication of parotitis epidemica (in Swedish). Nord Med 27: 1715–1717Google Scholar
  3. 3.
    Sultz HA, Hart BA, Zielezny M, Schlesinger ER (1975) Is mumps virus an etiologic factor in juvenile diabetes mellitus. J Pediatr 86: 654–656Google Scholar
  4. 4.
    Hyöty H, Leinikki P, Reunanen A et al. (1988) Mumps infections in the etiology of type 1 (insulin-dependent) diabetes. Diabetes Res 9: 111–116Google Scholar
  5. 5.
    Gamble DR (1980) Relation of antecedent illness to development of diabetes in children. BMJ 281: 99–101Google Scholar
  6. 6.
    Prince GA, Jenson AB, Billup L, Notkins AL (1978) Infection of human pancreatic beta cell cultures with mumps virus. Nature 271: 158–161Google Scholar
  7. 7.
    Parkkonen P, Hyöty H, Koskinen L, Leinikki P (1992) Mumps virus infects beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules. Diabetologia 35: 63–69Google Scholar
  8. 8.
    Ratzmann KP, Strese J, Witt S, Berling H, Keilacker H, Michaelis D (1984) Mumps infection and insulin-dependent diabetes mellitus. Diabetes Care 7: 170–173Google Scholar
  9. 9.
    Ratzmann KP, Strese J, Rjasanowski I et al. (1985) Metabolic, hormonal and immunological alterations in subjects with antecedent mumps infection. Exp Clin Endocrinol 86: 323–334Google Scholar
  10. 10.
    Helmke K, Otten A, Willems W (1980) Islet cell antibodies in children with mumps infection. Lancet II: 211–212Google Scholar
  11. 11.
    Helmke K, Otten A, Willems WR et al. (1986) Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination. Diabetologia 29: 30–33Google Scholar
  12. 12.
    Hyöty H, Huupponen T, Leinikki P (1985) Humoral immunity against viral antigens in insulin-dependent diabetes mellitus (IDDM) altered IgA class immune response against mumps virus. Clin Exp Immunol 60: 139–144Google Scholar
  13. 13.
    Toniolo A, Conaldi PG, Garzelli C et al. (1985) Role of antecedent mumps and reovirus infections on the development on type 1 (insulin-dependent) diabetes. Eur J Epidemiol 1: 172–179Google Scholar
  14. 14.
    Peltola H, Karanko V, Kurki T et al. (1986) Rapid effect on endemic measles, mumps, and rubella of nationwide vaccination programme in Finland. Lancet I: 137–139Google Scholar
  15. 15.
    Paunio M (1988) Compliance and vaccination coverage. Health Services Research by the National Board of Health in Finland, Helsinki, No. 47Google Scholar
  16. 16.
    Hyöty H, Räsänen L, Hiltunen M, Lehtinen M, Huupponen T, Leinikki P (1991) Decreased antibody reactivity to Epstein-Barr virus capsid antigen in type 1 (insulin-dependent) diabetes mellitus. APMIS 99: 359–363Google Scholar
  17. 17.
    Tuomilehto J, Lounamaa R, Tuomilehto-Wolf E et al. (1992) Epidemiology of childhood diabetes mellitus in Finland — background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35: 70–76Google Scholar
  18. 18.
    Julkunen I, Hautanen A, Keski-Oja J (1983) Interaction of viral envelope glycoproteins with fibronectin. Infect Immun 40: 876–881Google Scholar
  19. 19.
    Hyöty H, Huupponen T, Kotola L, Leinikki P (1986) Humoral immunity against viral antigens in type 1 diabetes: altered IgA class immune response against coxsackie B4 virus. Acta Path Microbiol Immunol Scand C 94: 83–88Google Scholar
  20. 20.
    Åkerblom HK, Reunanen A (1985) The epidemiology of insulin-dependent diabetes mellitus (IDDM) in Finland and in northern Europe. Diabetes Care 8 [Suppl 1]: 10–16Google Scholar
  21. 21.
    Reunanen A, Åkerblom HK, Tuomilehto J (1988) High incidence of insulin-dependent diabetes mellitus (IDDM) in children in Finland. Arctic Med Res 47 [Suppl 1]: 535–539Google Scholar
  22. 22.
    Hyöty H, Leinikki P, Hiltunen M, Huupponen T, and the Study Group of Childhood Diabetes in Finland (1990) Virus antibodies in type 1 diabetes in Finland. Diabetologia 33 [Suppl]: A67 (Abstract)Google Scholar
  23. 23.
    Bruserud Ø, Jervell J, Thorsby E (1985) HLA-DR3 and -DR4 control T-lymphocyte responses to mumps and coxsackie B4 virus: studies on patients with type 1 (insulin-dependent) diabetes and healthy subjects. Diabetologia 28: 420–426Google Scholar
  24. 24.
    Palmer JP, Cooney MK, Ward RH et al. (1982) Reduced coxsackie antibody titres in type 1 (insulin-dependent) diabetic patients presenting during an outbreak of coxsackie B3 and B4 infection. Diabetologia 22: 426–429Google Scholar
  25. 25.
    Diepersloot RJA, Bouter KP, Beyer WEP, Hoekstra JBL, Masurel N (1987) Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus. Diabetologia 30: 397–401Google Scholar
  26. 26.
    Panelius M, Salmi A, Halonen PE, Kivalo E, Rinne UK, Penttinen K (1973) Virus antibodies in serum specimens from patients with multiple sclerosis from siblings and matched controls. Acta Neurol Scand 49: 85–107Google Scholar
  27. 27.
    Fescharek R, Quast U, Maass G, Merkle W, Schwarz S (1990) Measles-mumps vaccination in the FRG: an empirical analysis after 14 years of use. II. Tolerability and analysis of spontaneously reported side-effects. Vaccine 8: 446–456Google Scholar
  28. 28.
    Miller E, Goldacre M, Pugh S et al. (1993) Risk of aseptic meningitis after measles, mumps and rubella vaccine in UK children. Lancet 341: 979–982Google Scholar
  29. 29.
    Koskiniemi M, Rautonen J, Lehtokoski-Lehtiniemi E, Vaheri A (1991) Epidemiology of encephalitis in children: a 20-year survey. Ann Neurology 29: 492–497Google Scholar
  30. 30.
    Rayfield EJ (1990) Effects of rubella virus infection on islet function. Cur Top Microbiol Immunol 156: 63–74Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • H. Hyöty
    • 1
  • M. Hiltunen
    • 1
  • A. Reunanen
    • 2
  • P. Leinikki
    • 3
  • T. Vesikari
    • 1
  • R. Lounamaa
    • 4
  • J. Tuomilehto
    • 4
  • H. K. Åkerblom
    • 5
  • the Childhoood Diabetes in Finland Study Group
  • L. Toivanen
  • E. A. Kaprio
  • A. Fagerlund
  • M. Flittner
  • B. Gustafsson
  • C. Häggqvist
  • A. Hakulinen
  • L. Herva
  • P. Hiltunen
  • T. Huhtamäki
  • N. -P. Huttunen
  • T. Huupponen
  • M. Hyttinen
  • T. Joki
  • R. Jokisalo
  • M. -L. Käär
  • S. Kallio
  • U. Kaski
  • M. Knip
  • L. Laine
  • J. Lappalainen
  • J. Mäenpää
  • A. -L. Mäkelä
  • K. Niemi
  • A. Niiranen
  • A. Nuuja
  • P. Ojajärvi
  • T. Otonkoski
  • K. Pihlajamäki
  • S. Pöntynen
  • J. Rajantie
  • J. Sankala
  • J. Schumacher
  • M. Sillanpää
  • M. -R. Ståhlberg
  • C. -H. Stråhlmann
  • T. Uotila
  • M. Väre
  • P. Varimo
  • G. Wettenstrand
  1. 1.Department of Biomedical SciencesUniversity of TampereTampereFinland
  2. 2.Research and Development Unit at the Social Insurance InstitutionHelsinkiFinland
  3. 3.HIV-departmentNational Public Health InstituteHelsinkiFinland
  4. 4.Department of EpidemiologyNational Public Health InstituteHelsinkiFinland
  5. 5.The Children's Hospital, Second Department of PaediatricsUniversity of HelsinkiHelsinkiFinland

Personalised recommendations