Role of Estrogen in Type 1 and Type 2 Diabetes Mellitus: A Review of Clinical and Preclinical Data

The incidence and prevalence of diabetes mellitus, and the cardiovascular complications associated with this disease, are rapidly increasing worldwide. Individuals with diabetes have a higher mortality rate due to cardiovascular diseases and a reduced life expectancy compared to those without diabetes. This poses a significant economic burden on health-care systems worldwide, making the diabetes epidemic a global health crisis. Sex differences in the presentation and outcome of diabetes do exist. Premenopausal women are protected from developing diabetes and its cardiovascular complications relative to males and postmenopausal women. However, women with diabetes tend to have a higher mortality as a result of cardiovascular complications than age-matched men. Despite this evidence, preclinical and clinical research looking at sex as a biologic variable in metabolic disorders and their cardiovascular complications is very limited. The aim of this review is to highlight the current knowledge of the potential protective role of estrogens in humans as well as rodent models of diabetes mellitus, and the possible pathways by which this protection is conferred. We stress the importance of increasing knowledge of sex-specific differences to facilitate the development of more targeted prevention strategies.