In T2DM hyperinsulinism (the stimulatory effects of insulin on bone formation) coupled with insulin resistance increases bone mass through effects on bone formation via IRS-1 and IRS-2 surface receptors on osteoblasts and by reducing the concentration of sex-hormone binding globulin (SHBG), which leads to increased concentrations of estradiol and testosterone [37]. This evidence concerns the gene SHBG and hyperinsulinism.