Diabetologia: Type 1 diabetes may not be a single disease but two distinct conditions

Scientists have found that type 1 diabetes may actually comprise not one disease but two genetically and biologically distinct conditions. Researchers from the United States and the United Kingdom reached this conclusion after conducting the first genome-wide analysis of patients with diabetes that took into account two HLA gene variants — DR3 and DR4. The findings were published in the journal Diabetologia.

The researchers compared genetic data from 9,091 people with type 1 diabetes and 14,157 healthy participants. The analysis revealed substantial differences between patients with the HLA-DR3 and HLA-DR4 variants, affecting not only genetic predisposition but also the possible mechanisms underlying the development of the disease.

With the HLA-DR3 variant, the researchers found an association with genes that influence the activity of mast cells — immune cells involved in inflammation and the body’s response to foreign substances.

“With HLA-DR4, by contrast, T cells appear to play a greater role. These cells are capable of directly attacking the body’s own cells. It is this autoimmune process that leads to the destruction of the insulin-producing beta cells in the pancreas,” the scientists explained.

Both genetic variants increase the likelihood of developing the same diagnosis, but the disease may be triggered by different biological mechanisms. According to the researchers, the differences between these groups are so pronounced that they could be considered separate subtypes of the disease.

“If the disease does indeed develop through several pathways, a single drug or prevention strategy may not work in the same way for different patients. In future clinical trials involving people with diabetes, we may take into account whether participants carry the HLA-DR3 or HLA-DR4 variants,” the researchers added.

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