Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children

S. M. Virtanen; E. Hyppönen; E. Läärä; P. Vähäsalo; P. Kulmala; K. Savola; L. Räsänen; A. Aro; M. Knip; H. K. Åkerblom; J. Tuomilehto; R. Lounamaa; L. Toivanen; J. Pitkäniemi; E. Virtala; 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; E. A. Kaprio; U. Kaski; L. Laine; J. Lappalainen; J. Mäenpää; A. L. Mäkelä; K. Niemi; A. Niiranen; 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; C. Wetterstrand; M. Hiltunen; H. Hurme; H. Hyöty; J. Ilonen; J. Karjalainen; P. Leinikki; A. Miettinen; T. Petäys; H. Reijonen; A. Reunanen; T. Saukkonen; E. Savilahti; E. Tuomilehto-Wolf

doi:10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children

S. M. Virtanen, E. Hyppönen, E. Läärä, P. Vähäsalo, P. Kulmala, K. Savola, L. Räsänen, A. Aro, M. Knip, H. K. Åkerblom, J. Tuomilehto, R. Lounamaa, L. Toivanen, J. Pitkäniemi, E. Virtala, A. Fagerlund, M. Flittner, B. Gustafsson, C. Häggqvist, A. HakulinenL. Herva, P. Hiltunen, T. Huhtamäki, N. P. Huttunen, T. Huupponen, M. Hyttinen, T. Joki, R. Jokisalo, M. L. Käär, S. Kallio, E. A. Kaprio, U. Kaski, L. Laine, J. Lappalainen, J. Mäenpää, A. L. Mäkelä, K. Niemi, A. Niiranen, 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, C. Wetterstrand, M. Hiltunen, H. Hurme, H. Hyöty, J. Ilonen, J. Karjalainen, P. Leinikki, A. Miettinen, T. Petäys, H. Reijonen, A. Reunanen, T. Saukkonen, E. Savilahti, E. Tuomilehto-Wolf

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82 % of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6 % (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5 % (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6 % (33/725) developed Type 1 DM during the total follow- up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (≤3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95 % confidence interval 1.3-11.7, p= 0.01). There was a non- significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95 % confidence interval 0.9- 8.4, p=0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.

Original language	English
Pages (from-to)	730-738
Number of pages	9
Journal	Diabetic Medicine
Volume	15
Issue number	9
DOIs	https://doi.org/10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C
Publication status	Published or Issued - 1998

Keywords

Autoantibodies
Children
Cow's milk
Diet
Infant feeding

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Endocrinology

Access to Document

10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

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Cite this

Virtanen, S. M., Hyppönen, E., Läärä, E., Vähäsalo, P., Kulmala, P., Savola, K., Räsänen, L., Aro, A., Knip, M., Åkerblom, H. K., Tuomilehto, J., Lounamaa, R., Toivanen, L., Pitkäniemi, J., Virtala, E., Fagerlund, A., Flittner, M., Gustafsson, B., Häggqvist, C., ... Tuomilehto-Wolf, E. (1998). Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children. Diabetic Medicine, 15(9), 730-738. https://doi.org/10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

Virtanen, S. M. ; Hyppönen, E. ; Läärä, E. ; Vähäsalo, P. ; Kulmala, P. ; Savola, K. ; Räsänen, L. ; Aro, A. ; Knip, M. ; Åkerblom, H. K. ; Tuomilehto, J. ; Lounamaa, R. ; Toivanen, L. ; Pitkäniemi, J. ; Virtala, E. ; Fagerlund, A. ; Flittner, M. ; Gustafsson, B. ; Häggqvist, C. ; Hakulinen, A. ; Herva, L. ; Hiltunen, P. ; Huhtamäki, T. ; Huttunen, N. P. ; Huupponen, T. ; Hyttinen, M. ; Joki, T. ; Jokisalo, R. ; Käär, M. L. ; Kallio, S. ; Kaprio, E. A. ; Kaski, U. ; Laine, L. ; Lappalainen, J. ; Mäenpää, J. ; Mäkelä, A. L. ; Niemi, K. ; Niiranen, A. ; Ojajärvi, P. ; Otonkoski, T. ; Pihlajamäki, K. ; Pöntynen, S. ; Rajantie, J. ; Sankala, J. ; Schumacher, J. ; Sillanpää, M. ; Ståhlberg, M. R. ; Stråhlmann, C. H. ; Uotila, T. ; Väre, M. ; Varimo, P. ; Wetterstrand, C. ; Hiltunen, M. ; Hurme, H. ; Hyöty, H. ; Ilonen, J. ; Karjalainen, J. ; Leinikki, P. ; Miettinen, A. ; Petäys, T. ; Reijonen, H. ; Reunanen, A. ; Saukkonen, T. ; Savilahti, E. ; Tuomilehto-Wolf, E. / Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus : A follow-up study in siblings of diabetic children. In: Diabetic Medicine. 1998 ; Vol. 15, No. 9. pp. 730-738.

@article{ecd5ec07a071409e904c6f5ee5798f29,

title = "Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children",

abstract = "Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82 % of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6 % (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5 % (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6 % (33/725) developed Type 1 DM during the total follow- up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (≤3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95 % confidence interval 1.3-11.7, p= 0.01). There was a non- significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95 % confidence interval 0.9- 8.4, p=0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.",

keywords = "Autoantibodies, Children, Cow's milk, Diet, Infant feeding",

author = "Virtanen, {S. M.} and E. Hypp{\"o}nen and E. L{\"a}{\"a}r{\"a} and P. V{\"a}h{\"a}salo and P. Kulmala and K. Savola and L. R{\"a}s{\"a}nen and A. Aro and M. Knip and {\AA}kerblom, {H. K.} and J. Tuomilehto and R. Lounamaa and L. Toivanen and J. Pitk{\"a}niemi and E. Virtala and A. Fagerlund and M. Flittner and B. Gustafsson and C. H{\"a}ggqvist and A. Hakulinen and L. Herva and P. Hiltunen and T. Huhtam{\"a}ki and Huttunen, {N. P.} and T. Huupponen and M. Hyttinen and T. Joki and R. Jokisalo and K{\"a}{\"a}r, {M. L.} and S. Kallio and Kaprio, {E. A.} and U. Kaski and L. Laine and J. Lappalainen and J. M{\"a}enp{\"a}{\"a} and M{\"a}kel{\"a}, {A. L.} and K. Niemi and A. Niiranen and P. Ojaj{\"a}rvi and T. Otonkoski and K. Pihlajam{\"a}ki and S. P{\"o}ntynen and J. Rajantie and J. Sankala and J. Schumacher and M. Sillanp{\"a}{\"a} and St{\aa}hlberg, {M. R.} and Str{\aa}hlmann, {C. H.} and T. Uotila and M. V{\"a}re and P. Varimo and C. Wetterstrand and M. Hiltunen and H. Hurme and H. Hy{\"o}ty and J. Ilonen and J. Karjalainen and P. Leinikki and A. Miettinen and T. Pet{\"a}ys and H. Reijonen and A. Reunanen and T. Saukkonen and E. Savilahti and E. Tuomilehto-Wolf",

year = "1998",

doi = "10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C",

language = "English",

volume = "15",

pages = "730--738",

journal = "Diabetic Medicine",

issn = "0742-3071",

publisher = "Wiley-Blackwell",

number = "9",

}

Virtanen, SM, Hyppönen, E, Läärä, E, Vähäsalo, P, Kulmala, P, Savola, K, Räsänen, L, Aro, A, Knip, M, Åkerblom, HK, Tuomilehto, J, Lounamaa, R, Toivanen, L, Pitkäniemi, J, Virtala, E, Fagerlund, A, Flittner, M, Gustafsson, B, Häggqvist, C, Hakulinen, A, Herva, L, Hiltunen, P, Huhtamäki, T, Huttunen, NP, Huupponen, T, Hyttinen, M, Joki, T, Jokisalo, R, Käär, ML, Kallio, S, Kaprio, EA, Kaski, U, Laine, L, Lappalainen, J, Mäenpää, J, Mäkelä, AL, Niemi, K, Niiranen, A, Ojajärvi, P, Otonkoski, T, Pihlajamäki, K, Pöntynen, S, Rajantie, J, Sankala, J, Schumacher, J, Sillanpää, M, Ståhlberg, MR, Stråhlmann, CH, Uotila, T, Väre, M, Varimo, P, Wetterstrand, C, Hiltunen, M, Hurme, H, Hyöty, H, Ilonen, J, Karjalainen, J, Leinikki, P, Miettinen, A, Petäys, T, Reijonen, H, Reunanen, A, Saukkonen, T, Savilahti, E & Tuomilehto-Wolf, E 1998, 'Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children', Diabetic Medicine, vol. 15, no. 9, pp. 730-738. https://doi.org/10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus : A follow-up study in siblings of diabetic children. / Virtanen, S. M.; Hyppönen, E.; Läärä, E.; Vähäsalo, P.; Kulmala, P.; Savola, K.; Räsänen, L.; Aro, A.; Knip, M.; Åkerblom, H. K.; Tuomilehto, J.; Lounamaa, R.; Toivanen, L.; Pitkäniemi, J.; Virtala, E.; Fagerlund, A.; Flittner, M.; Gustafsson, B.; Häggqvist, C.; Hakulinen, A.; Herva, L.; Hiltunen, P.; Huhtamäki, T.; Huttunen, N. P.; Huupponen, T.; Hyttinen, M.; Joki, T.; Jokisalo, R.; Käär, M. L.; Kallio, S.; Kaprio, E. A.; Kaski, U.; Laine, L.; Lappalainen, J.; Mäenpää, J.; Mäkelä, A. L.; Niemi, K.; Niiranen, A.; Ojajärvi, P.; Otonkoski, T.; Pihlajamäki, K.; Pöntynen, S.; Rajantie, J.; Sankala, J.; Schumacher, J.; Sillanpää, M.; Ståhlberg, M. R.; Stråhlmann, C. H.; Uotila, T.; Väre, M.; Varimo, P.; Wetterstrand, C.; Hiltunen, M.; Hurme, H.; Hyöty, H.; Ilonen, J.; Karjalainen, J.; Leinikki, P.; Miettinen, A.; Petäys, T.; Reijonen, H.; Reunanen, A.; Saukkonen, T.; Savilahti, E.; Tuomilehto-Wolf, E.

In: Diabetic Medicine, Vol. 15, No. 9, 1998, p. 730-738.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cow's milk consumption, disease-associated autoantibodies and Type 1 diabetes mellitus

T2 - A follow-up study in siblings of diabetic children

AU - Virtanen, S. M.

AU - Hyppönen, E.

AU - Läärä, E.

AU - Vähäsalo, P.

AU - Kulmala, P.

AU - Savola, K.

AU - Räsänen, L.

AU - Aro, A.

AU - Knip, M.

AU - Åkerblom, H. K.

AU - Tuomilehto, J.

AU - Lounamaa, R.

AU - Toivanen, L.

AU - Pitkäniemi, J.

AU - Virtala, E.

AU - Fagerlund, A.

AU - Flittner, M.

AU - Gustafsson, B.

AU - Häggqvist, C.

AU - Hakulinen, A.

AU - Herva, L.

AU - Hiltunen, P.

AU - Huhtamäki, T.

AU - Huttunen, N. P.

AU - Huupponen, T.

AU - Hyttinen, M.

AU - Joki, T.

AU - Jokisalo, R.

AU - Käär, M. L.

AU - Kallio, S.

AU - Kaprio, E. A.

AU - Kaski, U.

AU - Laine, L.

AU - Lappalainen, J.

AU - Mäenpää, J.

AU - Mäkelä, A. L.

AU - Niemi, K.

AU - Niiranen, A.

AU - Ojajärvi, P.

AU - Otonkoski, T.

AU - Pihlajamäki, K.

AU - Pöntynen, S.

AU - Rajantie, J.

AU - Sankala, J.

AU - Schumacher, J.

AU - Sillanpää, M.

AU - Ståhlberg, M. R.

AU - Stråhlmann, C. H.

AU - Uotila, T.

AU - Väre, M.

AU - Varimo, P.

AU - Wetterstrand, C.

AU - Hiltunen, M.

AU - Hurme, H.

AU - Hyöty, H.

AU - Ilonen, J.

AU - Karjalainen, J.

AU - Leinikki, P.

AU - Miettinen, A.

AU - Petäys, T.

AU - Reijonen, H.

AU - Reunanen, A.

AU - Saukkonen, T.

AU - Savilahti, E.

AU - Tuomilehto-Wolf, E.

PY - 1998

Y1 - 1998

N2 - Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82 % of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6 % (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5 % (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6 % (33/725) developed Type 1 DM during the total follow- up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (≤3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95 % confidence interval 1.3-11.7, p= 0.01). There was a non- significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95 % confidence interval 0.9- 8.4, p=0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.

AB - Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82 % of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6 % (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5 % (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6 % (33/725) developed Type 1 DM during the total follow- up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (≤3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95 % confidence interval 1.3-11.7, p= 0.01). There was a non- significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95 % confidence interval 0.9- 8.4, p=0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.

KW - Autoantibodies

KW - Children

KW - Cow's milk

KW - Diet

KW - Infant feeding

UR - http://www.scopus.com/inward/record.url?scp=15644363605&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

DO - 10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C

M3 - Article

C2 - 9737801

AN - SCOPUS:15644363605

VL - 15

SP - 730

EP - 738

JO - Diabetic Medicine

JF - Diabetic Medicine

SN - 0742-3071

IS - 9

ER -