In the present analysis, we investigated the expression of two candidate miRNAs, hsa-miR-191-3p and hsa-miR-375, in relation to biochemical parameters associated with early impairments in insulin sensitivity in a subgroup of only OW/Ob European children/adolescents, since obesity has a pivotal influence on glucose homeostasis and primary metabolic damage—the term “diabesity” has been coined in recent times [30]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.