Le May et al. (2006) reported that E2 acting through ER-α prevented pancreatic β cell apoptosis and diabetes in an insulin-deficient diabetic mouse model. Hormone replacement therapy has also been found to improve hyperglycemic control and to decrease the incidence of type 2 diabetes in postmenopausal women (Khoo and Perera 2005). In contrast, Lai et al. (1994) reported that women had a higher prevalence of diabetes mellitus than men after 40 years of age, especially in the postmenopausal phase (age > 50 years). Here, ESR1 is linked to type 2 diabetes mellitus.