Yiying Wang, Jennifer L Sargent, Chantal Mathieu, Elsa Vazquez-Arreola, Leigh Perreault, Ruth J F Loos, Lee-Ling Lim, Leontine Sandforth, Robert L Hanson, Stephanie Kullmann, Julia Sbierski-Kind, Sara Y Brucker, Martin Hrabé de Angelis, Fabian Theiss, Andrea Icks, Damon Mohebbi, Norbert Stefan, Viswanathan Mohan, Tiange Wang, Hubert Preissl, Michael Bergman, Jaakko Tuomilehto, Marie-France Hivert, Paul W Franks, Andreas L Birkenfeld
Type 2 diabetes (T2D) prevention efforts have largely focused on intervening when dysglycemia is already established. We propose that T2D prevention be reframed around prediabetes remission, with preservation and restoration of normoglycemia as the optimal clinical goal. The transition from normoglycemia through increasing dysglycemia to T2D is progressive and cumulatively shaped by biological, behavioral and environmental exposures across the life course. Prediabetes (intermediate hyperglycemia) remission is an achievable, pragmatic and measurable prevention target. Here we provide a life-course risk architecture for T2D integrating developmental, transitional and contextual determinants, defining critical windows of amplified metabolic vulnerability and potential restoration of normoglycemia. Precision prevention should target mechanistic heterogeneity, with aligned interventions that remain scalable, affordable and adaptable across socioeconomic settings. Our framework identifies ten priorities in T2D prevention, moving beyond traditional approaches toward context-specific, actionable interventions capable of altering the natural history of disease early in the life course and restoring metabolic health.