Weight Regain Reverses Caloric Restriction–Induced Benefits on the Insulin–IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial

Substantial weight loss followed by weight regain can attenuate or reverse CR-induced benefits on key regulators of the insulin-IGF-1 nutrient-sensing pathway and markers of biological aging. Sustained, moderate weight loss more effectively improves insulin resistance and maintains favorable hormonal profiles linked to type 2 diabetes risk and aging biology.