In support of our hypothesis that a trend-free ΔG0 would allow for an uncompromised evaluation of beta cell function, this trend-free ΔG0 was, nevertheless, associated with a substantial rate of increase in AIRg in the obese, indicating that, rather than IVGTT overloading, the elevated AIRg in the obese must be due to adaptation to the insulin resistance of obesity, either by increased sensitivity of the beta cells to glucose or by reduced insulin elimination, as previously reported15,16. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.