On the biological side, premenopausal women have greater insulin sensitivity than men do, likely due to the protective effect of estrogen; however, obesity can weaken this effect, and men show worse insulin secretion dysfunction at the same obesity level, so a WHtR increase is associated with greater metabolic risk for men (Gado et al., 2024). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.