Conversely, during prolonged intra-portal hypoinsulinemia (e.g., malnutrition, anorexia nervosa, and T1D), IGFBP-1 levels increase several-fold (7), leading to the increased complex formation between IGF-I and IGFBP-1 and clear reductions in free IGF-I (“brake” effect) (Figure 2). Here, IGF1 is linked to nutritional deficiency disease.