In addition, severe insulin resistance, defined by a fasting insulin level of 50 μIU/mL or greater,26 was significantly more prevalent in individuals with obesity classes 4 to 5 (40.63%; 95% CI, 25.52%-57.74%) than in those with obesity classes 1 to 3 (7.82%; 95% CI, 6.17%-9.87%) or no obesity (0.70%; 95% CI, 0.45%-1.08%) and was also significantly higher compared with class 3 separately (Figure 3E and eFigure 5 in Supplement 1). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.