INS and neoplasm: This is illustrated by the results of a study on a cohort of patients with a GIST, showing that the patients with a relatively high tumor load (i.e., total diameter >12 cm) exhibited significantly higher pretreatment plasma levels of IGF‐IIE [68–87] than subjects with a lower tumor load.59 Presumably, when a certain threshold level of big IGF‐II in the circulation is exceeded, the low affinity signaling via the IR‐B becomes increasingly important, which in particular causes insulin‐like metabolic changes.