Insulin is produced in the beta-cells in pancreatic islets of Langerhans. The insulin is needed for glucose to enter all cells and be used as a source of energy. An individual with diabetes suffers from insulin deficiency and hence an increased blood glucose.
Type 1 diabetes (T1D) is a chronic disease caused by destruction of the insulin producing beta-cells in the pancreas. The incidence of T1D has increased rapidly, especially in the Western world and among young children. The pathogenesis of T1D is not fully understood, but the beta-cells are believed to be destroyed by an autoimmune process initiated years before the onset of T1D. During this pre-clinical period, autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the tyrosine phosphatase-like protein IA-2 (IA-2A) can be detected and are used to identify individuals at risk of T1D. The major genetic determinant for T1D is the HLA class II genes, but also polymorphism in the insulin gene and CTLA-4 gene are associated with T1D. The risk genes cannot explain the rapid increase in incidence of T1D, therefore a role for different environmental factors has been suggested. The aim was to study the prevalence of beta-cell autoantibodies in children from the general population in relation to known genetic and environmental risk factors, and in young patients with T1D in high and low incidence areas.Short duration of breast-feeding was associated with an increased risk of developing beta-cell autoantibodies in children from the general population at 5-6 years of age…
Contents
REVIEW OF THE LITERATURE
HISTORY OF TYPE 1 DIABETES
DEFINITION AND DIAGNOSIS OF DIABETES
EPIDEMIOLOGY OF TYPE 1 DIABETES
SOME ASPECTS OF THE IMMUNE SYSTEM
PATHOGENESIS OF TYPE 1 DIABETES
Islet cell antibodies (ICA)
Autoantibodies to glutamic acid decarboxylase (GADA)
Autoantibodies to tyrosine phosphatase-like protein IA-2 (IA-2A )
Insulin as an autoantigen
Autoantibodies to insulin (IAA)
Analyses of beta-cell autoantibodies – methodological issues
GENETIC RISK OF TYPE 1 DIABETES
Hereditary risk of T1D
The human leukocyte antigen complex (HLA)
The insulin gene (INS)
The cytotoxic T lymphocyte associated antigen -4 gene (CTLA-4)
The immunological effects of the genetic risk factors
PREDICTION OF TYPE 1 DIABETES
Prediction and prevention studies
ENVIRONMENTAL FACTORS
MECHANISMS OF ALLERGY AND ATOPY
CELIAC DISEASE
HYPOTHESES & AIMS OF THE THESIS
SUBJECTS & METHODS
STUDY POPULATIONS
Paper I: Diabetes-related autoantibodies in non-diabetic children
Paper II: Swedish and Lithuanian children with type 1 diabetes
Paper III: Breast-feeding & autoantibodies in children from the general population
Paper IV: Risk genes & autoantibodies in children from the general population
METHODS
Paper I: Diabetes-related autoantibodies in non-diabetic children
Paper II: Swedish and Lithuanian children with type 1 diabetes
Paper III: Breast-feeding & autoantibodies in children from the general population
Paper IV: Risk genes & autoantibodies in children from the general population
STATISTICAL METHODS
ETHICAL CONSIDERATIONS
Paper I: Diabetes-related autoantibodies in non-diabetic children
Paper II: Swedish and Lithuanian children with type 1 diabetes
Paper III: Breast-feeding & autoantibodies in children from the general population
Paper IV: Risk genes & autoantibodies in children from the general population
RESULTS & DISCUSSION
PAPER I: DIABETES-RELATED AUTOANTIBODIES IN NON-DIABETIC CHILDREN
Prevalence & fluctuation of beta-cell autoantibodies
Dietary factors & beta-cell autoantibodies
Ear infection or atopy & beta-cell autoantibodies
Discussion
PAPER II: SWEDISH AND LITHUANIAN CHILDREN WITH TYPE 1 DIABETES
Beta-cell autoantibodies in patients and family members
Patient age and gender & beta-cell autoantibodies
Parent’s age and autoimmunity & beta-cell autoantibodies in the patients
Beta-cell autoantibodies & clinical characteristics
Beta-cell autoantibodies & genetic risk of type 1 diabetes
Discussion
PAPER III: BREAST-FEEDING & AUTOANTIBODIES IN CHILDREN FROM THE GENERAL POPULATION
Descriptives
Duration of total breast-feeding & beta-cell autoantibodies
Duration of exclusive breast-feeding & beta-cell autoantibodies
Introduction of cow milk proteins & beta-cell autoantibodies
External factors & beta-cell autoantibodies
Discussion
PAPER IV: RISK GENES & AUTOANTIBODIES IN CHILDREN FROM THE GENERAL POPULATION
Frequencies of HLA haplotypes and INS-23 genotypes
Beta-cell autoantibodies in relation to HLA haplotypes or genotypes
Beta-cell autoantibodies in relation to polymorphism in the insulin gene70
Discussion
SUMMARY & CONCLUSIONS
ACKNOWLEDGEMENTS
REFERENCES
Author: Holmberg, Hanna
Source: Linköping University
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