Sex differences in type 2 diabetes: an opportunity for personalized medicine

Over the past several decades, substantial ground has been gained in understanding the biology of sex differences. With new mandates to include sex as a biological variable in NIH-funded research, greater knowledge is forthcoming on how sex chromosomes, sex hormones, and social and societal differences between sexes can affect the pathophysiology of health and disease. A detailed picture of how biological sex impacts disease pathophysiology will directly inform clinicians in their treatment approaches and challenge canonical therapeutic strategies. Thus, a profound opportunity to explore sex as a variable in personalized medicine now presents itself. While many sex differences are apparent in humans and have been described at length, we are only beginning to see how such differences impact disease progression, treatment efficacy, and outcomes in obesity, type 2 diabetes, and cardiovascular disease. Here, we briefly present the most salient and convincing evidence of sex differences in type 2 diabetes detection, diagnostics, disease course, and therapeutics. We then offer commentary on how this evidence can inform clinicians on how to approach the clinical workup and management of different patients with diabetes. Finally, we discuss some gaps that remain in the literature and propose several research questions to guide basic and translational researchers as they continue in this growing area of scientific exploration.