To learn on the mechanisms of insulin resistance in obesity-driven type 2 diabetes three groups were investigated: 1) lean subjects with normal glycaemia (Lean); 2) obese subjects who are hyperinsulinemic and insulin resistant but that maintain a good glycaemic control (Obese-IR); and obese subjects with recently diagnosed type 2 diabetes (Obese-T2D). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.