Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. This leads to little or no insulin production, a hormone needed to convert blood sugar into energy. While there is currently no cure, significant research explores methods for preventing its onset or slowing its progression. T1D’s development involves genetic predispositions, environmental factors, and immune system responses.
Understanding Who Is At Risk
Identifying individuals at high risk for T1D is an important step, as prevention strategies are targeted towards these groups. Two primary indicators help assess this risk: genetic predisposition and the presence of islet autoimmunity.
Genetic predisposition plays a substantial role, with genes in the Human Leukocyte Antigen (HLA) region accounting for a significant portion of T1D’s familial clustering. Specific HLA class II genes, such as variations in HLA-DRB1, HLA-DQA1, and HLA-DQB1, are strongly associated with increased susceptibility. Certain high-risk haplotypes exist, particularly the DR3/DR4 genotype. However, having these genes alone is not enough for T1D to develop; other factors are necessary.
Islet autoimmunity is another key indicator, identified by the presence of autoantibodies in the blood. These autoantibodies, such as those against insulin (IAA), glutamic acid decarboxylase (GAD65), insulinoma-associated antigen-2 (IA-2), and zinc transporter 8 (ZnT8), signal that the immune system has begun attacking pancreatic beta cells. Detecting two or more of these autoantibodies indicates a preclinical stage of T1D, even before symptoms appear or blood sugar levels become abnormal. Individuals with multiple autoantibodies, particularly those who develop them earlier in life, face a higher risk of progressing to symptomatic T1D.
Strategies to Prevent Autoimmunity
This section focuses on primary prevention, aiming to prevent the immune system from developing autoimmunity against beta cells in individuals without autoantibodies. Non-pharmaceutical approaches are currently being investigated.
Dietary strategies, such as vitamin D supplementation, have been explored for their potential to reduce autoimmune responses. Vitamin D helps modulate the immune system and has anti-inflammatory properties. Studies suggest that adequate vitamin D intake, particularly in early childhood, might reduce T1D risk. Omega-3 fatty acids, found in fish oil, are also known for their anti-inflammatory and immunomodulatory properties and are being studied for their potential to slow or halt T1D progression.
Probiotics, which introduce beneficial bacteria to the gut, are being investigated for their role in preventing T1D. Research suggests that an imbalance in gut bacteria, known as dysbiosis, may contribute to the autoimmune response. Probiotics may help restore healthy gut microbiota, improve gut barrier function, and modulate the immune system, potentially reducing inflammation and increasing beneficial metabolites. Some studies have observed that children who developed T1D had less bacterial diversity and more inflammation-triggering bacteria in their guts.
Breastfeeding has been suggested to have a protective effect against T1D, potentially due to its influence on the infant’s immune system development and gut microbiome. Human milk contains biologically active substances like antibodies, cytokines, and hormones that may help regulate the infant immune system and protect against infections. Pooled analyses suggest that exclusive breastfeeding may reduce diabetes risk by about 15%.
Rotavirus vaccination has been hypothesized as a potential factor in T1D prevention. Some research suggests a possible link between rotavirus infections and T1D development, due to similarities between viral sequences and T1D autoantigen sequences. While some studies report a decrease in T1D incidence rates in vaccinated children, others find no such association, making the overall effect of rotavirus vaccination on T1D risk unclear.
Other environmental factors, such as early exposure to certain foods like gluten or cow’s milk, and various viral infections including enteroviruses, rubella, and Epstein-Barr virus, are areas of ongoing research. The progressive increase in T1D incidence over the years points to the role of these environmental factors in triggering or accelerating the disease process in genetically susceptible individuals. However, for many of these factors, the evidence is still being gathered and can be controversial.
Strategies to Delay Disease Onset
This section focuses on secondary prevention, aiming to delay or prevent the clinical onset of T1D in individuals who have already developed islet autoimmunity but are not yet symptomatic. Advancements in this area have brought promising pharmaceutical interventions.
Teplizumab (Tzield) represents a significant breakthrough, being the first FDA-approved drug to delay the onset of clinical (Stage 3) T1D in individuals aged 8 years and older with Stage 2 T1D. This monoclonal antibody targets CD3 molecules on the surface of T cells, which are immune cells responsible for attacking the insulin-producing beta cells. By binding to CD3, teplizumab modulates T cell activity, reducing their attack on beta cells and helping to preserve insulin production. Clinical trials demonstrated that a single 14-day course of teplizumab infusion could delay T1D diagnosis by an average of two years, with some cases showing an even longer delay.
Oral insulin has been investigated as a way to “retrain” the immune system and induce tolerance to insulin. Repeated oral administration of insulin, an autoantigen, might introduce a protective immunity and stop the immune system’s attack. While a large-scale study indicated that oral insulin generally did not delay or prevent T1D in the overall study population, a subgroup analysis suggested a potential benefit for participants with higher levels of insulin autoantibodies. Further studies are exploring this potential in specific high-risk groups.
Other immunotherapies are under investigation to modulate the immune response and protect beta cells. These include various types of anti-CD3 antibodies, similar to teplizumab, and other approaches that aim to balance immune responses. Therapies targeting cytokines, signaling molecules involved in inflammation, are being explored. Some studies are also examining the use of granulocyte colony-stimulating factor (GCSF) and other antigen-specific therapies designed to induce immune tolerance.
The field of T1D prevention is dynamic, with numerous ongoing clinical trials exploring new pharmaceutical interventions. Researchers are continuously working to identify new drugs and combination therapies that can effectively delay or prevent T1D onset in at-risk individuals. These trials are crucial for understanding disease progression and developing future strategies to reduce the burden of T1D.