How HLA Genes Shape Type 1 Diabetes Risk—and When Other Autoimmune Diseases Appear Together

Type 1 diabetes is an autoimmune disease, meaning the immune system mistakenly attacks the insulin-producing cells in the pancreas. Unlike Type 2 diabetes, which is primarily linked to lifestyle factors, Type 1 has a strong genetic component. A major piece of this genetic puzzle involves genes called HLA class II genes, which help the immune system recognize what belongs in the body and what doesn't.

Researchers have long known that certain HLA gene variants are more common in people with Type 1 diabetes than in the general population. A new study from Eastern Croatia provides fresh evidence about which specific HLA variants and combinations matter most.

Researchers examined 149 patients with Type 1 diabetes and compared their HLA genes to a control group of 111 unrelated blood donors from the same region. They focused on three HLA loci: HLA-DRB1, HLA-DQA1, and HLA-DQB1.

Two genetic patterns showed particularly strong associations with Type 1 diabetes. The HLA-DRB1*03 allele and the three-gene combination HLA-DQA1*05-DQB1*02-DRB1*03 (called the DR3-DQ2 haplotype) were both significantly more common in people with Type 1 diabetes than in the control group. Similarly, the HLA-DRB1*04 variant and the DR4-DQ8 haplotype also showed strong associations with Type 1 diabetes.

One striking finding was that more than one-third of the Type 1 diabetes patients in the study—about 37%—had developed at least one additional autoimmune disease. The most common was thyroid disease, affecting nearly a quarter of all patients. Other conditions included gastrointestinal problems like celiac disease (7.4%) and skin conditions (6.0%).

This clustering of autoimmune diseases is not random. The researchers found that certain HLA patterns were associated with specific combinations of diseases, suggesting that the same genetic factors that increase Type 1 diabetes risk can also influence the likelihood of other autoimmune conditions developing alongside it. Understanding these connections may eventually help doctors identify which patients are at higher risk for developing multiple autoimmune diseases.

This study adds to a growing body of evidence showing that HLA genes are a crucial part of Type 1 diabetes development. However, it's important to understand what this research does and does not tell us. While certain HLA variants significantly increase the risk of Type 1 diabetes, they are not destiny. Many people carry these genetic markers without ever developing the disease, and genetic factors alone cannot predict who will get Type 1 diabetes.

For patients and families already living with Type 1 diabetes, this research underscores the importance of screening for other autoimmune conditions. If you have Type 1 diabetes, talking with your healthcare provider about whether screening for thyroid disease or celiac disease makes sense for you or your children is a practical next step.

Source: Frontiers in endocrinology. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.