Diabetes diagnosed earlier in life confers a substantial lifetime risk of complications, premature cardiovascular disease, kidney failure and early mortality. While advances in glucose management have improved outcomes, significant residual risk remains, highlighting the need for therapies that target the underlying mechanisms driving disease initiation and progression. This presentation will discuss two emerging therapeutic strategies aimed at altering the trajectory of diabetes and its complications in young people.
The first focuses on the receptor for advanced glycation end products (RAGE), an innate immune receptor implicated in type 1 diabetes (T1D) pathogenesis. Preclinical studies have demonstrated that modulation of RAGE signalling using soluble RAGE-based biologics can prevent T1D onset, preserve pancreatic β-cell mass and improve endogenous insulin secretion. These findings support the development of novel RAGE-targeted therapies, including biologics delivered via next-generation intradermal microarray patch technologies and orally administered RAGE antagonists, with the goal of providing accessible and scalable approaches for T1D prevention.
The second focuses on diabetic kidney disease (DKD), the leading cause of premature death in people with diabetes. Recent studies from our group demonstrate that systemic mitochondrial dysfunction is evident in young people with diabetes before clinically overt kidney disease develops and is associated with markers of future renal decline. These observations suggest that mitochondrial dysfunction is an early and potentially modifiable therapeutic target. The presentation will highlight emerging clinical and translational studies evaluating mitochondrial biomarkers and the potential of mitochondria-targeted therapies such as KH176 to reduce residual kidney and cardiovascular risk.
Together, these programs illustrate how mechanistically targeted therapies may enable earlier intervention, disease interception and improved long-term outcomes for people living with diabetes.