INS and obesity due to melanocortin 4 receptor deficiency: Interestingly, METRNL has been proposed to have positive effects on glucose homeostasis [60,76], and METRNL levels have been positively associated with insulin sensitivity [61] and negatively correlated with HbA1c [77], and several studies have reported lower circulating levels in people with obesity, overweight, prediabetes, and T2DM, in comparison with controls [70,72,77,78,79,80].