Early-life factors contributing to type 1 diabetes

Abstract

The incidence of type 1 diabetes has increased since the mid-twentieth century at a rate that is too rapid to be attributed to genetic predisposition alone. While the disease can occur at any age, mounting evidence from longitudinal cohort studies of at-risk children indicate that type 1 diabetes associated autoantibodies can be present from the first year of life, and that those who develop type 1 diabetes at a young age have a more aggressive form of the disease. This corroborates the hypothesis that environmental exposures in early life contribute to type 1 diabetes risk, whether related to maternal influences on the fetus during pregnancy, neonatal factors or later effects during infancy and early childhood. Studies to date show a range of environmental triggers acting at different time points, suggesting a multifactorial model of genetic and environmental factors in the pathogenesis of type 1 diabetes, which integrally involves a dialogue between the immune system and pancreatic beta cells. For example, breastfeeding may have a weak protective effect on type 1 diabetes risk, while use of an extensively hydrolysed formula does not. Additionally, exposure to being overweight pre-conception, both in utero and postnatally, is associated with increased risk of type 1 diabetes. Epidemiological, clinical and pathological studies in humans support a role for viral infections, particularly enteroviruses, in type 1 diabetes, but definitive proof is lacking. The role of the early microbiome and its perturbations in islet autoimmunity and type 1 diabetes is the subject of investigation in ongoing cohort studies. Understanding the interactions between environmental exposures and the human genome and metagenome, particularly across ethnically diverse populations, will be critical for the development of future strategies for primary prevention of type 1 diabetes.

Histone Deacetylase 3 Aggravates Type 1 Diabetes Mellitus by Inhibiting Lymphocyte Apoptosis Through the microRNA-296-5p/Bcl-xl Axis

“…Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by immune-mediated destruction of pancreatic islet β-cells (Vatanen et al, 2018). The incidence of T1DM has drastically increased since 1950 worldwide (Craig et al, 2019). Patients with T1DM possess a higher risk to suffer from epilepsy compared with healthy individuals (Dafoulas et al, 2017).…”

Endocrine Disrupting Chemicals and Type 1 Diabetes

“…Serological islet autoantibodies are directed against glutamic acid decarboxylase 65 (GAD), tyrosine phosphatase-like insulinoma antigen 2 (IA2), insulin (IAA), and β-cells-specific zinc transporter 8 (ZnT8) [14,15]. The autoimmune process against β-cells seems to be also determined by environmental triggers [16] whose potential role was supported by the low concordance of T1D incidence among monozygotic twins [17] and by the rise of T1D incidence in industrial countries. Moreover, it is nowadays known that in genetically susceptible subjects who migrate from low to high risk areas for T1D the disease incidence tends to increase; it seems acceptable that immigration is associated with exposure to new environmental factors contributing to the development of T1D [18,19].…”

Childhood type 1 diabetes: an environment-wide association study across England

“…Genetic predisposition plays a role in the development of type 1 diabetes. Although more than 40 risk loci are associated with type 1 diabetes [3], most individuals who possess type 1 diabetes risk genes do not, however, develop diabetes [3][4][5], suggesting additional factors are needed to trigger and drive the disease process.…”

“…Various environmental triggers of type 1 diabetes have been proposed [3][4][5]. Viral infections have long been associated with type 1 diabetes [6].…”