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The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study.
J Clin Endocrinol Metab 2001; 86(10):4782-8JC

Abstract

Little is known about the timing of the etiological events and the preclinical process of type 1 diabetes during the first years of life in the general population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of beta-cell autoimmunity and the development of type 1 diabetes were monitored from birth. Of 25,983 newborn infants, 2,448 genetically susceptible children were monitored for islet cell antibodies (ICA) at 3- to 6-month intervals. If an infant seroconverted to ICA positivity, all his/her samples were also analyzed for insulin autoantibodies (IAA), antibodies to the 65-kDa isoform of glutamic acid decarboxylase, and antibodies to the protein tyrosine phosphatase-related IA-2 molecule. Fifteen children of those who carried the high-risk genotype (2.7%) and 23 of those who carried the moderate-risk genotype (1.2%; P = 0.019) tested positive for ICA at least once. Among those who showed positivity for at least 2 antibodies during the observation period (25 of 38), IAA appeared as the first or among the first antibodies in 22 children (88%) and emerged earlier than the other antibodies (P < 0.019 or less). The first autoantibodies appeared in the majority of the children in the fall and winter (30 of 38 vs. 8 of 38 in the spring and summer, P < 0.001). These observations suggest that young children in the general population with a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diabetes show signs of beta-cell autoimmunity proportionally more often than those with a moderate genetic risk. IAA emerge as the first detectable antibody more commonly than any other antibody specificity, implying that insulin may be the primary antigen in most cases of human type 1 diabetes associated with the DR4-DQB1*0302 haplotype. The seasonal variation in the emergence of the first signs of beta-cell autoimmunity suggests that infectious agents may play a role in the induction of such autoimmunity.

Authors+Show Affiliations

The Juvenile Diabetes Research Foundation Center for Type 1 Diabetes Prevention in Finland, Department of Pediatrics, Medical School, University of Tampere, FIN-33014 Tampere, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11600541

Citation

Kimpimäki, T, et al. "The First Signs of Beta-cell Autoimmunity Appear in Infancy in Genetically Susceptible Children From the General Population: the Finnish Type 1 Diabetes Prediction and Prevention Study." The Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, 2001, pp. 4782-8.
Kimpimäki T, Kupila A, Hämäläinen AM, et al. The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab. 2001;86(10):4782-8.
Kimpimäki, T., Kupila, A., Hämäläinen, A. M., Kukko, M., Kulmala, P., Savola, K., ... Knip, M. (2001). The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. The Journal of Clinical Endocrinology and Metabolism, 86(10), pp. 4782-8.
Kimpimäki T, et al. The First Signs of Beta-cell Autoimmunity Appear in Infancy in Genetically Susceptible Children From the General Population: the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab. 2001;86(10):4782-8. PubMed PMID: 11600541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. AU - Kimpimäki,T, AU - Kupila,A, AU - Hämäläinen,A M, AU - Kukko,M, AU - Kulmala,P, AU - Savola,K, AU - Simell,T, AU - Keskinen,P, AU - Ilonen,J, AU - Simell,O, AU - Knip,M, PY - 2001/10/16/pubmed PY - 2001/11/3/medline PY - 2001/10/16/entrez SP - 4782 EP - 8 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 86 IS - 10 N2 - Little is known about the timing of the etiological events and the preclinical process of type 1 diabetes during the first years of life in the general population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of beta-cell autoimmunity and the development of type 1 diabetes were monitored from birth. Of 25,983 newborn infants, 2,448 genetically susceptible children were monitored for islet cell antibodies (ICA) at 3- to 6-month intervals. If an infant seroconverted to ICA positivity, all his/her samples were also analyzed for insulin autoantibodies (IAA), antibodies to the 65-kDa isoform of glutamic acid decarboxylase, and antibodies to the protein tyrosine phosphatase-related IA-2 molecule. Fifteen children of those who carried the high-risk genotype (2.7%) and 23 of those who carried the moderate-risk genotype (1.2%; P = 0.019) tested positive for ICA at least once. Among those who showed positivity for at least 2 antibodies during the observation period (25 of 38), IAA appeared as the first or among the first antibodies in 22 children (88%) and emerged earlier than the other antibodies (P < 0.019 or less). The first autoantibodies appeared in the majority of the children in the fall and winter (30 of 38 vs. 8 of 38 in the spring and summer, P < 0.001). These observations suggest that young children in the general population with a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diabetes show signs of beta-cell autoimmunity proportionally more often than those with a moderate genetic risk. IAA emerge as the first detectable antibody more commonly than any other antibody specificity, implying that insulin may be the primary antigen in most cases of human type 1 diabetes associated with the DR4-DQB1*0302 haplotype. The seasonal variation in the emergence of the first signs of beta-cell autoimmunity suggests that infectious agents may play a role in the induction of such autoimmunity. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/11600541/The_first_signs_of_beta_cell_autoimmunity_appear_in_infancy_in_genetically_susceptible_children_from_the_general_population:_the_Finnish_Type_1_Diabetes_Prediction_and_Prevention_Study_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.86.10.7907 DB - PRIME DP - Unbound Medicine ER -