Revisiting the role of the insulin gene in type 1 diabetes: implications for pathogenesis, complications, therapy and a cure

Abstract

Type 1 diabetes (T1D) is an autoimmune disease where the immune system attacks insulin-producing beta-cells, leading to insulin insufficiency and uncontrolled blood glucose levels. With no cure available, patients rely on intensive and burdensome insulin therapy, which often fails to maintain blood glucose levels within target ranges. This increases the risk of complications like hypoglycemia, diabetic ketoacidosis, and chronic diabetic conditions. My research shows that beta-cells actively contribute to T1D development, indicating immunotherapy alone cannot cure this disease. Beta-cells must also be treated to reduce their stress levels, improve their function, and make them less likely to trigger immune responses, thereby promoting their survival. Genetic modification might achieve this. We discovered that a natural insulin gene variant improves beta-cell function, reduces stress, and lowers immunogenicity. Patients who develop T1D despite this protective gene variant rarely develop complications. Due to such differences among patients, not everyone will benefit from the same treatment. Patients with similar disease characteristics can be grouped into endotypes, allowing for targeted therapeutic interventions. The goals and endpoints of therapies should be revised and expanded to be meaningful for patients. This would enable therapies to reach patients more quickly and frequently, with more realistic expectations.