From survival to freedom: redefining success in type 1 diabetes.

Abstract

Type 1 diabetes has shifted from a condition once associated with early mortality to a chronic disease owing to the development of intensive insulin therapy, continuous glucose monitoring, and hybrid closed-loop systems. Despite near-normoglycaemia becoming an attainable target, residual excess mortality and cardiovascular risk persist. These outcomes are thought to reflect the long-term biological legacy of earlier dysglycaemia, including metabolic and epigenetic memory associated with inflammatory and vascular vulnerability. As survival for people with type 1 diabetes lengthens, morbidity increasingly shifts towards cognitive decline, depression, infections, and cancer, whereas the lived burden of daily disease management remains high. As evidence suggests that further reductions in HbA_1c do not translate into proportional improvements in outcomes at the population level, the next therapeutic frontier becomes physiological resilience: interventions that restore endogenous regulation, reduce glycaemic variability, and dampen inflammatory stress, thereby approximating a more physiological metabolic state. β-cell replacement-via pancreas or islet transplantation and emerging stem cell-derived implants-should be judged less by mean HbA_1c and more by durability, safety, C-peptide preservation, time in (tight) range, and validated patient-reported outcomes. Regulatory and economic frameworks must consequently embrace multidimensional benefits. Within this evolving framework, success is measured not only by longer survival, but also by improved physiological control achieved with minimal toxicity and reduced cognitive burden. This Personal View argues for reframing therapeutic success in type 1 diabetes by shifting the focus from glycaemic metrics alone to the restoration of endogenous regulation and physiological resilience-outcomes operationalised as sustained metabolic stability, protection from severe hypoglycaemia, and a substantial reduction in cognitive and therapeutic burden.