These observations suggest that NK activity abnormalities especially in long-standing T1D patients, seem to be a consequence of metabolic disorders after the process leading to beta-cell destruction [46], a consequence of immunomodulatory/immunosuppressing effects of insulin treatment [121,122,123,124,125,126] or a consequence of exhaustion of NK cells, which can be observed in the course of chronic infection [127]. Here, INS is linked to type 1 diabetes mellitus.