Environmental and Genetic Factors Investigated
Although type 1 diabetes (T1D) affects more than 8 million people worldwide, with large expected increases in coming years, the underlying trigger of the complex metabolic disorder remains undefined. Researchers of a new study are exploring the various factors, as well as their interactions, potentially at play in T1D susceptibility.
Outside of genetics, which has a well-documented link to the risk of T1D, the group detailed available research spanning a variety of factors, including viral infections, pesticide exposure, and the gut microbiome.
Environmental factors that include viral infections, such as enteroviruses, have been shown to infiltrate pancreatic beta cells and induce autoimmunity against them. Data have shown presence of enterovirus proteins in the pancreas at the onset of T1D. Publishing their insights in Frontiers in Endocrinology, the researchers noted that enteroviruses, along with others, have similar structural components as pancreatic beta cell antigens, leading the immune system to unintentionally attack insulin-producing beta cells when activated to fight off the virus.
Other environmental factors highlighted by the researchers include pesticide exposure, vitamin D deficiency, and lifestyle and dietary factors. Further research digging into the exact mechanisms by which these factors, including viruses, influence T1D are needed. Further research into pesticide exposure, for example, can help inform public health recommendations and preventive strategies, particularly for those exposed to pesticides at work or those living in agricultural areas.
The researchers also highlighted the potential relationship between the gene-environment dynamic and how it influences the development of T1D.
“Despite the individual roles of genetic susceptibility and environmental risk factors, it is still unknown what triggers pancreatic β cell destruction and development of T1D in some patients,” described the researchers, noting that not all patients harboring genetic variants associated with T1D develop the condition. “There is an emerging hypothesis that the interaction of environmental factors with genetic predisposition plays a crucial role in the pathophysiology of T1D. Environmental factors may exaggerate the effect of gene variants inducing autoimmunity and leading to the clinical manifestations of T1D.”
Research has pointed to epigenetic modulators, together with environmental factors, as being critical in regulating gene expression and cellular phenotype. Areas of research have focused on mechanisms like DNA methylation alterations, highlighting ties between anomalous patterns in genes and immune function, as well as insulin regulation, in the condition.
The gut microbiome and its role in T1D has also been explored. Changes in the microbiome of the gut have been shown to affect mucosal integrity and immune tolerance, subsequently increasing the risk of T1D. Compared with healthy patients, those with T1D have been found to have an increase of Bacteroides and Bifidobacterium spp and a decrease of Lactococcus spp.
“Although some progress has been made in understanding the role of the gut microbiome in T1D, there are still many unanswered questions,” wrote the researchers. “Understanding these mechanisms is crucial for developing potential therapeutic interventions. Furthermore, there is a need to perform more longitudinal studies to understand how early-life exposures and changes in the gut microbiome contribute to the development of T1D, especially using emerging techniques such as omics technology. The information derived from these studies would provide insights into the temporal dynamics of microbiome changes and their association with T1D onset.”
Reference
Mittal R, Camick N, Lemos J, Hirani K. Gene-environment interaction in the pathophysiology of type 1 diabetes. Front Endocrinol (Lausanne). 2024:15:1335435. doi:10.3389/fendo.2024.1335435
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