Type 1 Diabetes May Actually Be Two Different Diseases, Massive International Study Finds

ScienceAlert reports on a genome-wide association study suggesting that type 1 diabetes may include at least two biologically distinct subtypes, rather than being one uniform disease pathway. Researchers in the United States and United Kingdom analyzed genetic data from 9,091 people with type 1 diabetes and 14,157 controls, separating patients according to two known high-risk HLA genetic backgrounds: HLA-DR3 and HLA-DR4. The study was published in *Diabetologia*.

The key finding is that the two HLA backgrounds were associated with different genetic signals and immune mechanisms. In HLA-DR3-associated type 1 diabetes, the genetic results pointed more strongly toward mast cells, immune cells linked with inflammation and allergic responses. In HLA-DR4-associated disease, T cells appeared more central; these are the immune cells already known to attack pancreatic beta cells in type 1 diabetes. The researchers argue that the genetic distinction between DR3 and DR4 type 1 diabetes is large enough to suggest different sub-forms of the disease.

This matters because type 1 diabetes prevention and treatment trials may need to account for a person’s genetic background. If the disease can arise through different immune routes, a therapy that works for one subgroup may not work as well for another. The article notes that future studies could separate clinical-trial results by HLA-DR3 and HLA-DR4 status, improve risk prediction models, and follow patients over time to understand how genetics, autoantibodies, and environmental exposures interact before clinical diabetes develops.