Abstract
Type 1 Diabetes (T1D) results from autoimmune destruction of insulin producing pancreatic ß-cells. This disease, with a peak incidence in childhood, causes the lifelong need for insulin injections and necessitates careful monitoring of blood glucose levels. However, despite the current insulin therapies, it still shortens life expectancy due to complications affecting multiple organs. Recently, the incidence of T1D in childhood has increased by 3–5% per year in most developed Western countries. The heterogeneity of the disease process is supported by the findings of follow-up studies started early in infancy. The development of T1D is usually preceded by the appearance of autoantibodies targeted against antigens expressed in the pancreatic islets. The risk of T1D increases significantly with an increasing number of positive autoantibodies. The order of autoantibody appearance affects the disease risk. Genetic susceptibility, mainly defined by the human leukocyte antigen (HLA) class II gene region and environmental factors, is important in the development of islet autoimmunity and T1D. Environmental factors, mainly those linked to the changes in the gut microbiome as well as several pathogens, especially viruses, and diet are key modulators of T1D. The aim of this paper is to expand the understanding of the aetiology and pathogenesis of T1D in childhood by detailed description and comparison of factors affecting the progression from the islet autoimmunity to T1D in children.
Highlights
Type 1 diabetes (T1D) is a chronic endocrine disease that results from autoimmune destruction of insulin-producing β-cells in the pancreas after the asymptomatic period of various duration [1,2,3].The development of T1D is a heterogeneous process, usually proceeded by the appearance of islet-specific autoantibodies against β-cells structures
Among the autoantibodies which are construed as a sign of ongoing β-cells destruction, islet cell cytoplasmic autoantibodies (ICA), and biochemical autoantibodies targeted to insulin (IAA), islet antigen-2 protein (IA-2A), glutamic acid decarboxylase (GADA) and zinc transporter 8 (ZnT8A) are the best characterised [4]
This review describes the genetic, immunological and environmental risk factors affecting the progression of islet autoimmunity and progression to clinical T1D in children
Summary
Type 1 diabetes (T1D) is a chronic endocrine disease that results from autoimmune destruction of insulin-producing β-cells in the pancreas after the asymptomatic period of various duration [1,2,3]. The two most common autoantibodies present at seroconversion in childhood are IAA and GADA, whereas IA-2A and ZnT8A autoantibodies appear as the first ones in a relatively small proportion They are all common at the diagnosis of the disease [5,6]. The observed risk of T1D is time-constant for high IA-2A levels but decrease over time for IAA and GADA [14] Detailed analysis of this complex relationship, including ZnT8 autoantibody, is still lacking. This review describes the genetic, immunological and environmental risk factors affecting the progression of islet autoimmunity and progression to clinical T1D in children. The primary etiologic classification was suggested for the first time already in 1951, in a study in which the discrimination between insulin-dependent and non-insulin-dependent diabetes mellitus was stated for the first time [38]
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