A study with 100 Caucasian non-diabetic, overweight volunteers with first-degree type 2 diabetic relatives undergoing 9 months of lifestyle intervention demonstrates that circulating POA is a strong and independent determinant of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp tests, implying its critical role in the pathophysiology of insulin resistance in humans (46). The gene discussed is INS; the disease is Insulin resistance.