Beyond HbA1c: insulin resistance as a modifier of early vascular injury in adolescents with type 1 diabetes

Type 1 diabetes (T1D), which commonly presents in childhood or adolescence, is an autoimmune disease in which immune-mediated destruction of pancreatic β-cells leads to absolute or near-absolute insulin deficiency and lifelong dependence on insulin administration. During adolescence, pubertal changes and increased insulin requirements can worsen glycemic instability and raise the risk of vascular complications, such as cardiovascular disease. Although hyperglycemia promotes vascular injury, different early vascular phenotypes in adolescents with similar hemoglobin A 1 c (HbA 1 c) levels suggest that additional mechanisms may influence vascular risk. Insulin resistance (IR) may be an important contributor because insulin sensitivity declines during puberty, and this decline is associated with oxidative stress, altered endothelial signaling, inflammation, and adiposity. However, establishing a causal relationship between IR and early vascular injury in T1D remains challenging. This review examines the link between IR and early vascular injury in adolescents with T1D and emphasizes endothelial dysfunction, arterial stiffness, and biomarkers that may connect metabolic stress to vascular damage. Evidence from metabolic, endothelial, inflammatory, omics-based, and imaging studies supports an association between IR, inflammatory pathways, endothelial injury, and impaired vascular repair. Overall, IR, inflammatory, endothelial, and vascular imaging measures may complement HbA 1 c when studying vascular risk in adolescents with T1D. Whether they provide additional diagnostic or prognostic value beyond HbA 1 c is still unknown.