Anaarthi Srinivas

Background: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease in which T-cells attack and destroy the insulin-producing cells of the pancreas¹. As of 2021, 304,000 children and adolescents (those younger than 20) in the US had diagnosed T1DM; additionally, 5.7% of all adults with diabetes had T1DM³. While correlations between viral triggers, genetic predispositions, and the onset of T1DM have been explored, the exact etiology of T1DM remains elusive. In this review, we explore the viral causes, genomic etiology, familial concordance, and immunological mechanism of action of Type 1 Diabetes Mellitus (T1DM).

Methods: An online search in the PubMed database was conducted from 2020-2025 using the following keywords/phrases in conjunction with the phrase “Type 1 Diabetes Mellitus”: “Viral Triggers”, “Familial Concordance ”, “Genetic Etiology”, “T-Regulatory cells”. Dates were expanded to include dates prior to 2020 to understand the evolution of T1DM etiology research.

Results: Viral triggers have long been associated with the onset of T1DM, including enteroviruses such as coxsackie b virus (CVB) and cytomegalovirus (CMV)⁵. Despite this, a causal relationship between coxsackie b viruses has not been established². Furthermore, CMV, in older literature, has been associated with the triggering of T1DM⁷. This contrasts with newer studies, which have seen a statistically significant negative correlation between the onset of T1DM in genetically predisposed children who have and have not had CMV infections in early childhood⁴. Additionally, T1DM has long been associated with the genetic risk factors of variations of the HLA class 2 DR-DQ loci⁸. Non-HLA genes have been identified to correlate with the onset of T1DM, including single nucleotide polymorphisms (SNPs)⁸. Finally, developing therapies include immunomodulation of beta-cell autoreactive T-cells via IFN-gamma primed megakaryocytes, which have been shown to increase T-regs and lead to pancreatic angiogenesis⁶.

Conclusions: The reviewed literature demonstrates that the etiology of T1DM is complex and multifactorial, with a variety of genetic and viral risk factors contributing to T1DM’s onset. Implications of the viral etiology suggest that viral vaccines would be a promising strategy for mitigating the development of T1DM. Similarly, further identification of genes correlated with T1DM could increase and standardize T1DM screening measures for infants/children through genetic analysis, and prevent T1DM associated comorbidities, such as diabetic ketoacidosis (DKA).

Works Cited

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2. Carré, A., Vecchio, F., Malin Flodström-Tullberg, You, S., & Mallone, R. (2023). Coxsackievirus and Type 1 Diabetes: Diabetogenic Mechanisms and Implications for Prevention. Endocrine Reviews, 44(4). https://doi.org/10.1210/endrev/bnad007
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