On the other hand, the chronic elevation of insulin, such as that observed in genetic syndromes of severe insulin resistance (Type A syndrome with Acanthosis Nigricans, Alstrom syndrome, or Congenital Generalized Lipodystrophy), may positively affect bone through “spillover” mechanisms involving the insulin-like growth factor-1 (IGF-1) receptor Reviewed in Ref. Here, IGF1 is linked to acanthosis nigricans.