The main aim of the proposed research is to obtain new information about the etiology of insulin-dependent diabetes mellitus (IDDM) in Finland, where the incidence of IDDM is highest in the world and still increasing. It is assumed that understanding why Finland has the highest incidence rate of IDDM in the world and why the incidence rate is still increasing among Finnish children will lead to the determination of the etiology of IDDM. Since genetic susceptibility to IDDM has been measured by complete HLA genotyping and putative environmental determinants have also been measured, there exists an unique opportunity to estimate the interaction between genetic and environmental factors. The investigators' DiMe study represents the largest family study of IDDM with detailed data on epidemiology, HLA genetics and putative environmental risk factors. During the next three years of support requested, the primary goals will be the analysis of the data collected during the previous years of the study. Data on new cases of childhood IDDM registered in Finland nationwide will be used to determine long-term temporal trends, seasonality, spatial variation, and space-time clustering of IDDM. Also, international comparative analyses will be continued. The genetic family data on HLA-A, C, B, DR, DQ markers and entire HLA haplotypes will be analyzed in detail. Attention will be particularly paid to the haplotype versus single allele effects, and to haplotypes transmitted from a parent with IDDM to the child with IDDM. The role of class I antigens for the risk of IDDM will be evaluated in detail. The case-control studies will be analyzed by addressing the role of various dietary factors, viral infections, and vaccinations in the development of IDDM. In utero effects will be investigated in three ways: comparing the birth weight and length in IDDM cases and controls, comparing the reported diet between mothers of cases and controls, and comparing virus antibody levels in sera between the cases and controls collected during pregnancy. New information will be obtained about the role of genetic and environmental factors in the development of IDDM in 9,463 offspring of 5,261 IDDM patients in a population-based prospective study to determine the reasons for sex-associated effects for the transmission of genetic susceptibility to IDDM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037957-09
Application #
2458750
Study Section
Special Emphasis Panel (ZRG4-EDC-1 (02))
Program Officer
Akolkar, Beena
Project Start
1987-05-01
Project End
1998-07-31
Budget Start
1997-08-15
Budget End
1998-07-31
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Public Health Institute
Department
Type
DUNS #
City
Helsinki
State
Country
Finland
Zip Code
00300
Juusola, Matilda; Parkkola, Anna; Härkönen, Taina et al. (2016) Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced ?-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes. Diabetes Care 39:118-21
Uusitalo, Liisa; Knip, Mikael; Kenward, Michael G et al. (2005) Serum alpha-tocopherol concentrations and risk of type 1 diabetes mellitus: a cohort study in siblings of affected children. J Pediatr Endocrinol Metab 18:1409-16
Pitkaniemi, Janne; Onkamo, Paivi; Tuomilehto, Jaakko et al. (2004) Increasing incidence of Type 1 diabetes--role for genes? BMC Genet 5:5
Pitkaniemi, Janne; Hakulinen, Timo; Nasanen, Jurkka et al. (2004) Class I and II HLA genes are associated with susceptibility and age at onset in Finnish families with type 1 diabetes. Hum Hered 57:69-79
Hoppu, S; Ronkainen, M S; Kulmala, P et al. (2004) GAD65 antibody isotypes and epitope recognition during the prediabetic process in siblings of children with type I diabetes. Clin Exp Immunol 136:120-8
Rytkonen, M; Moltchanova, E; Ranta, J et al. (2003) The incidence of type 1 diabetes among children in Finland--rural-urban difference. Health Place 9:315-25
Toivonen, A M; Kulmala, P; Savola, K et al. (2003) Soluble adhesion molecules in pre-clinical Type 1 diabetes: a prospective study. Diabetologia 46:492-5
Mrena, S; Savola, K; Kulmala, P et al. (2003) Natural course of preclinical type 1 diabetes in siblings of affected children. Acta Paediatr 92:1403-10
Mrena, S; Savola, K; Kulmala, P et al. (2003) Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children. J Clin Endocrinol Metab 88:2682-9
Knip, Mikael; Kukko, Marika; Kulmala, Petri et al. (2002) Humoral beta-cell autoimmunity in relation to HLA-defined disease susceptibility in preclinical and clinical type 1 diabetes. Am J Med Genet 115:48-54

Showing the most recent 10 out of 84 publications