SHBG and Hyperinsulinemia: Moreover, the sex steroid hormone-binding globulin (SHBG) - T2DM relationship is an independent factor in deciding the sex hormones levels in both men and women [47], Metabolic dysfunction with hyperglycemia, insulin resistance, and associated hyperinsulinemia in the early stages of T2DM [48] suppress the SHBG level [47], which will eventually increase the sex hormones level, could be the reason for the more prominent estrogen-mediated vagotonic responses observed in the diabetic population compared to the control female in their proliferative phase.