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Published in: Diabetologia 7/2005

01-07-2005 | Article

Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation

Authors: H. Viskari, J. Ludvigsson, R. Uibo, L. Salur, D. Marciulionyte, R. Hermann, G. Soltesz, M. Füchtenbusch, A.-G. Ziegler, A. Kondrashova, A. Romanov, B. Kaplan, Z. Laron, P. Koskela, T. Vesikari, H. Huhtala, M. Knip, H. Hyöty

Published in: Diabetologia | Issue 7/2005

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Abstract

Aims/hypothesis

We have previously observed an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. The aim of this study was to analyse whether maternal enterovirus antibody status, which reflects both the frequency of enterovirus infections and the protection conferred by the mother on the offspring, also correlates with the incidence of type 1 diabetes.

Methods

Maternal enterovirus antibodies were analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden using enzyme immunoassay and neutralisation assays. Comparable samples were also taken between 1999 and 2001 in countries with a lower incidence of diabetes (Estonia, Germany, Hungary, Israel, Lithuania, Russia).

Results

A clear decrease was observed in maternal enterovirus antibody levels over the past 20 years (p<0.0001). The frequency of enterovirus antibodies was higher in countries with a low or intermediate incidence of type 1 diabetes compared with high-incidence countries (p<0.0001).

Conclusions/interpretation

These findings are in line with our previous observations supporting the hypothesis that a low frequency of enterovirus infection in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses.
Literature
1.
go back to reference Podar T, Solntsev A, Karvonen M et al (2001) Increasing incidence of childhood-onset type I diabetes in 3 Baltic countries and Finland 1983–1998. Diabetologia 44(Suppl 3):B17–B20PubMed Podar T, Solntsev A, Karvonen M et al (2001) Increasing incidence of childhood-onset type I diabetes in 3 Baltic countries and Finland 1983–1998. Diabetologia 44(Suppl 3):B17–B20PubMed
2.
go back to reference Gale EA (2002) The rise of childhood type 1 diabetes in the 20th century. Diabetes 51:3353–3361PubMed Gale EA (2002) The rise of childhood type 1 diabetes in the 20th century. Diabetes 51:3353–3361PubMed
3.
go back to reference Kondrashova A, Reunanen A, Romanov A et al (2005) A sixfold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 37:67–72CrossRef Kondrashova A, Reunanen A, Romanov A et al (2005) A sixfold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 37:67–72CrossRef
4.
go back to reference Virtanen SM, Aro A (1994) Dietary factors in the aetiology of diabetes. Ann Med 26:469–478PubMed Virtanen SM, Aro A (1994) Dietary factors in the aetiology of diabetes. Ann Med 26:469–478PubMed
5.
6.
go back to reference Viskari HR, Koskela P, Lönnrot M et al (2000) Can enterovirus infections explain the increasing incidence of type 1 diabetes? Diabetes Care 23:414–416PubMed Viskari HR, Koskela P, Lönnrot M et al (2000) Can enterovirus infections explain the increasing incidence of type 1 diabetes? Diabetes Care 23:414–416PubMed
7.
go back to reference Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed Viskari H, Ludvigsson J, Uibo R et al (2004) Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project. J Med Virol 72:610–617CrossRefPubMed
8.
go back to reference Lönnrot M, Knip M, Marciulionyte D et al (1999) Enterovirus antibodies in relation to islet cell antibodies in two populations with high and low incidence of type 1 diabetes. Diabetes Care 22:2086–2088PubMed Lönnrot M, Knip M, Marciulionyte D et al (1999) Enterovirus antibodies in relation to islet cell antibodies in two populations with high and low incidence of type 1 diabetes. Diabetes Care 22:2086–2088PubMed
9.
go back to reference Pallansch MA, Roos RP (2001) Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. In: Knipe DM, Howley PM (eds) Fields virology. Lippincott Williams &Wilkins, Philadelphia, pp 723–775 Pallansch MA, Roos RP (2001) Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. In: Knipe DM, Howley PM (eds) Fields virology. Lippincott Williams &Wilkins, Philadelphia, pp 723–775
10.
go back to reference Morens D, Pallansh M (1995) Epidemiology. In: Rotbart H (ed) Human enterovirus infections. ASM, Washington DC, pp 3–23 Morens D, Pallansh M (1995) Epidemiology. In: Rotbart H (ed) Human enterovirus infections. ASM, Washington DC, pp 3–23
11.
go back to reference Alexander LM, Heaven A, Tennant A, Morris R (1992) Symptomatology of children in contact with sea water contaminated with sewage. J Epidemiol Community Health 46:340–344PubMed Alexander LM, Heaven A, Tennant A, Morris R (1992) Symptomatology of children in contact with sea water contaminated with sewage. J Epidemiol Community Health 46:340–344PubMed
12.
go back to reference van Olphen M, Kapsenberg JG, van de Baan E, Kroon WA (1984) Removal of enteric viruses from surface water at eight waterworks in The Netherlands. Appl Environ Microbiol 47:927–932PubMed van Olphen M, Kapsenberg JG, van de Baan E, Kroon WA (1984) Removal of enteric viruses from surface water at eight waterworks in The Netherlands. Appl Environ Microbiol 47:927–932PubMed
13.
go back to reference Ozere RL, Faulkner R, Van Rooyen CE (1961) Enteroviruses in sewage and epidemic poliomyelitis in eastern Canada. Can Med Assoc J 85:1419–1424PubMed Ozere RL, Faulkner R, Van Rooyen CE (1961) Enteroviruses in sewage and epidemic poliomyelitis in eastern Canada. Can Med Assoc J 85:1419–1424PubMed
14.
go back to reference Hovi T, Stenvik M, Rosenlew M (1996) Relative abundance of enterovirus serotypes in sewage differs from that in patients: clinical and epidemiological implications. Epidemiol Infect 116:91–97PubMed Hovi T, Stenvik M, Rosenlew M (1996) Relative abundance of enterovirus serotypes in sewage differs from that in patients: clinical and epidemiological implications. Epidemiol Infect 116:91–97PubMed
15.
go back to reference Grew N, Gohd RS, Arguedas J, Kato JI (1970) Enteroviruses in rural families and their domestic animals. Am J Epidemiol 91:518–526PubMed Grew N, Gohd RS, Arguedas J, Kato JI (1970) Enteroviruses in rural families and their domestic animals. Am J Epidemiol 91:518–526PubMed
16.
go back to reference Kadoi K, Suzuki H, Nishio O (2001) Isolation of coxsackievirus B5 from pigs. New Microbiol 24:217–222PubMed Kadoi K, Suzuki H, Nishio O (2001) Isolation of coxsackievirus B5 from pigs. New Microbiol 24:217–222PubMed
17.
go back to reference Waldman EA, Moreira RC, Saez SG et al (1996) Human enterovirus infection in stray dogs. Some aspects of interest to public health. Rev Inst Med Trop Sao Paulo 38:157–161PubMed Waldman EA, Moreira RC, Saez SG et al (1996) Human enterovirus infection in stray dogs. Some aspects of interest to public health. Rev Inst Med Trop Sao Paulo 38:157–161PubMed
18.
go back to reference Zinkernagel RM (2001) Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med 345:1331–1335CrossRefPubMed Zinkernagel RM (2001) Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med 345:1331–1335CrossRefPubMed
19.
20.
go back to reference Roivainen M, Alfthan G, Jousilahti P, Kimpimäki M, Hovi T, Tuomilehto J (1998) Enterovirus infections as a possible risk factor for myocardial infarction. Circulation 98:2534–2537PubMed Roivainen M, Alfthan G, Jousilahti P, Kimpimäki M, Hovi T, Tuomilehto J (1998) Enterovirus infections as a possible risk factor for myocardial infarction. Circulation 98:2534–2537PubMed
21.
go back to reference Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA (1999) Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 37:1288–1293PubMed Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA (1999) Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 37:1288–1293PubMed
22.
go back to reference Sadeharju K, Lönnrot M, Kimpimäki T et al (2001) Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children. Diabetologia 44:818–823CrossRefPubMed Sadeharju K, Lönnrot M, Kimpimäki T et al (2001) Enterovirus antibody levels during the first two years of life in prediabetic autoantibody-positive children. Diabetologia 44:818–823CrossRefPubMed
23.
go back to reference Kurikka S, Olander RM, Eskola J, Käyhty H (1996) Passively acquired anti-tetanus and anti-Haemophilus antibodies and the response to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infancy. Pediatr Infect Dis J 15:530–535CrossRefPubMed Kurikka S, Olander RM, Eskola J, Käyhty H (1996) Passively acquired anti-tetanus and anti-Haemophilus antibodies and the response to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infancy. Pediatr Infect Dis J 15:530–535CrossRefPubMed
24.
go back to reference Roivainen M, Knip M, Hyöty H et al (1998) Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78CrossRefPubMed Roivainen M, Knip M, Hyöty H et al (1998) Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78CrossRefPubMed
25.
go back to reference Green A, Patterson CC (2001) Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia 44(Suppl 3):B3–B8CrossRefPubMed Green A, Patterson CC (2001) Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia 44(Suppl 3):B3–B8CrossRefPubMed
26.
go back to reference Altman DG (1991) Non-parametric test for ordered groups. In: Altman DG (ed) Practical statistics for medical research. Chapman and Hall, London, pp 215–217 Altman DG (1991) Non-parametric test for ordered groups. In: Altman DG (ed) Practical statistics for medical research. Chapman and Hall, London, pp 215–217
27.
go back to reference Altman D, Altman DG, Bryant T, Gardner M, Gardner MJ, Machin D (2000) Statistics with confidence, 2nd edn. BMJ Books, London Altman D, Altman DG, Bryant T, Gardner M, Gardner MJ, Machin D (2000) Statistics with confidence, 2nd edn. BMJ Books, London
28.
go back to reference Staines A, Bodansky HJ, McKinney PA et al (1997) Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density. Int J Epidemiol 26:1307–1313CrossRefPubMed Staines A, Bodansky HJ, McKinney PA et al (1997) Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density. Int J Epidemiol 26:1307–1313CrossRefPubMed
29.
go back to reference Parslow RC, McKinney PA, Law GR, Staines A, Williams R, Bodansky HJ (1997) Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis. Diabetologia 40:550–556CrossRefPubMed Parslow RC, McKinney PA, Law GR, Staines A, Williams R, Bodansky HJ (1997) Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis. Diabetologia 40:550–556CrossRefPubMed
30.
go back to reference Schober E, Rami B, Waldhoer T (2003) Small area variation in childhood diabetes mellitus in Austria: links to population density, 1989 to 1999. J Clin Epidemiol 56:269–273CrossRefPubMed Schober E, Rami B, Waldhoer T (2003) Small area variation in childhood diabetes mellitus in Austria: links to population density, 1989 to 1999. J Clin Epidemiol 56:269–273CrossRefPubMed
31.
go back to reference Patterson CC, Carson DJ, Hadden DR (1996) Epidemiology of childhood IDDM in Northern Ireland 1989–1994: low incidence in areas with highest population density and most household crowding. Northern Ireland Diabetes Study Group. Diabetologia 39:1063–1069PubMed Patterson CC, Carson DJ, Hadden DR (1996) Epidemiology of childhood IDDM in Northern Ireland 1989–1994: low incidence in areas with highest population density and most household crowding. Northern Ireland Diabetes Study Group. Diabetologia 39:1063–1069PubMed
32.
go back to reference Parslow RC, McKinney PA, Law GR, Bodansky HJ (2001) Population mixing and childhood diabetes. Int J Epidemiol 30:533–538; discussion 538–539CrossRefPubMed Parslow RC, McKinney PA, Law GR, Bodansky HJ (2001) Population mixing and childhood diabetes. Int J Epidemiol 30:533–538; discussion 538–539CrossRefPubMed
33.
go back to reference Karvonen M, Rusanen J, Sundberg M et al (1997) Regional differences in the incidence of insulin-dependent diabetes mellitus among children in Finland from 1987 to 1991. Childhood Diabetes in Finland (DiMe) Study Group. Ann Med 29:297–304PubMed Karvonen M, Rusanen J, Sundberg M et al (1997) Regional differences in the incidence of insulin-dependent diabetes mellitus among children in Finland from 1987 to 1991. Childhood Diabetes in Finland (DiMe) Study Group. Ann Med 29:297–304PubMed
34.
go back to reference Rytkönen M, Moltchanova E, Ranta J, Taskinen O, Tuomilehto J, Karvonen M (2003) The incidence of type 1 diabetes among children in Finland—rural–urban difference. Health Place 9:315–325CrossRefPubMed Rytkönen M, Moltchanova E, Ranta J, Taskinen O, Tuomilehto J, Karvonen M (2003) The incidence of type 1 diabetes among children in Finland—rural–urban difference. Health Place 9:315–325CrossRefPubMed
35.
go back to reference Kaila B, Taback SP (2001) The effect of day care exposure on the risk of developing type 1 diabetes: a meta-analysis of case-control studies. Diabetes Care 24:1353–1358PubMed Kaila B, Taback SP (2001) The effect of day care exposure on the risk of developing type 1 diabetes: a meta-analysis of case-control studies. Diabetes Care 24:1353–1358PubMed
36.
go back to reference Pundziute-Lyckå A, Urbonaite B, Dahlquist G (2000) Infections and risk of type I (insulin-dependent) diabetes mellitus in Lithuanian children. Diabetologia 43:1229–1234CrossRefPubMed Pundziute-Lyckå A, Urbonaite B, Dahlquist G (2000) Infections and risk of type I (insulin-dependent) diabetes mellitus in Lithuanian children. Diabetologia 43:1229–1234CrossRefPubMed
37.
go back to reference Blom L, Nystrom L, Dahlquist G (1991) The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood. Diabetologia 34:176–181CrossRefPubMed Blom L, Nystrom L, Dahlquist G (1991) The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood. Diabetologia 34:176–181CrossRefPubMed
38.
go back to reference Gibbon C, Smith T, Egger P, Betts P, Phillips D (1997) Early infection and subsequent insulin dependent diabetes. Arch Dis Child 77:384–385PubMed Gibbon C, Smith T, Egger P, Betts P, Phillips D (1997) Early infection and subsequent insulin dependent diabetes. Arch Dis Child 77:384–385PubMed
39.
go back to reference Dahlquist GG, Patterson C, Soltesz G (1999) Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. Diabetes Care 22:1698–1702PubMed Dahlquist GG, Patterson C, Soltesz G (1999) Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. Diabetes Care 22:1698–1702PubMed
40.
go back to reference EURODIAB Substudy 2 Study Group (2000) Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. Diabetologia 43:47–53 EURODIAB Substudy 2 Study Group (2000) Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. Diabetologia 43:47–53
41.
go back to reference Juhela S, Hyöty H, Roivainen M, Härkonen T, Putto-Laurila A, Simell O, Ilonen J (2000) T-cell responses to enterovirus antigens in children with type 1 diabetes. Diabetes 49:1308–1313PubMed Juhela S, Hyöty H, Roivainen M, Härkonen T, Putto-Laurila A, Simell O, Ilonen J (2000) T-cell responses to enterovirus antigens in children with type 1 diabetes. Diabetes 49:1308–1313PubMed
42.
go back to reference Bruserud O, 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 28:420–426CrossRefPubMed Bruserud O, 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 28:420–426CrossRefPubMed
43.
go back to reference D’Alessio DJ (1992) A case-control study of group B Coxsackievirus immunoglobulin M antibody prevalence and HLA-DR antigens in newly diagnosed cases of insulin-dependent diabetes mellitus. Am J Epidemiol 135:1331–1338PubMed D’Alessio DJ (1992) A case-control study of group B Coxsackievirus immunoglobulin M antibody prevalence and HLA-DR antigens in newly diagnosed cases of insulin-dependent diabetes mellitus. Am J Epidemiol 135:1331–1338PubMed
44.
go back to reference Sadeharju K, Knip M, Hiltunen M, Åkerblom HK, Hyöty H (2003) The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens. Diabetologia 46:1100–1105CrossRefPubMed Sadeharju K, Knip M, Hiltunen M, Åkerblom HK, Hyöty H (2003) The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens. Diabetologia 46:1100–1105CrossRefPubMed
45.
go back to reference Rønningen KS, Keiding N, Green A (2001) Correlations between the incidence of childhood-onset type I diabetes in Europe and HLA genotypes. Diabetologia 44(Suppl 3):B51–B59PubMed Rønningen KS, Keiding N, Green A (2001) Correlations between the incidence of childhood-onset type I diabetes in Europe and HLA genotypes. Diabetologia 44(Suppl 3):B51–B59PubMed
46.
go back to reference Dahlquist G, Mustonen L (2000) Analysis of 20 years of prospective registration of childhood onset diabetes time trends and birth cohort effects. Swedish Childhood Diabetes Study Group. Acta Paediatr 89:1231–1237CrossRefPubMed Dahlquist G, Mustonen L (2000) Analysis of 20 years of prospective registration of childhood onset diabetes time trends and birth cohort effects. Swedish Childhood Diabetes Study Group. Acta Paediatr 89:1231–1237CrossRefPubMed
Metadata
Title
Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation
Authors
H. Viskari
J. Ludvigsson
R. Uibo
L. Salur
D. Marciulionyte
R. Hermann
G. Soltesz
M. Füchtenbusch
A.-G. Ziegler
A. Kondrashova
A. Romanov
B. Kaplan
Z. Laron
P. Koskela
T. Vesikari
H. Huhtala
M. Knip
H. Hyöty
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1780-9

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