However, subgroup analysis by metabolic status demonstrated a significant and positive correlation between circulating irisin and insulin levels in studies that included patients with metabolic disorders (including three studies that enrolled PCOS patients, 1 study that enrolled NAFLD patients, one study that included individuals with mild hypercholesterolemia and one study that included people with BF% > 30). This evidence concerns the gene FNDC5 and familial hypercholesterolemia.