Impaired glucose metabolism: Time for sex-based medicine?

Abstract

In the new era of precision medicine, the investigation of disparities is mandatory to tailor preventive strategies. Mounting evidence supports the existence of substantial sex differences in the microvascular and macrovascular complications of diabetes. Biological differences between men and women can contribute to sex differences in the occurrence and prognosis of diabetes. In general, women tend to have a higher percentage of body fat and often develop peripheral adiposity, whereas men tend to accumulate visceral adipose tissue. Women also have less muscle mass than men and therefore have less muscle available for the uptake of glucose. Sex hormones represent another factor that may differentially regulate glycaemic control in men and women. Lower circulating androgen concentrations have been associated with a higher cardiometabolic risk in men, while higher levels of total estradiol have been associated with increased risk of diabetes in women. Differing diets and physical activities, and genetic and epigenetic factors, can also explain the sex differences in the development of diabetes. The risk of cardiometabolic disorders may differ not only for men and women with diabetes, but also for prediabetic men and women. Prediabetes, which is characterized by impaired glucose metabolism, precedes the development of type 2 diabetes (DM2) and is a risk factor for cardiometabolic disorders. However, the effect of sex differences on the prognosis of prediabetes is controversial and needs to be addressed in order to improve personalized care. Previous studies have evaluated the risk of cardiometabolic disorders in prediabetic men and women and results have been inconsistent. The discrepancy may be due to differences across populations and study designs, the use of different diagnostic criteria for prediabetes and heterogeneous definitions of clinical endpoints. Some studies analysed sex as a covariate without providing sex-specific associations, and did not simultaneously test for multiple outcomes. In this context, a comprehensive and simultaneous investigation of cardiometabolic disorders in prediabetic men and women within the same population, according to various diagnostic criteria, could be crucial to improving the management and prognosis of prediabetic patients. In this issue of the European Journal of Preventive Cardiology, Parizadeh et al. have found meaningful sex differences in the association between prediabetes and some cardiometabolic outcomes across the diagnostic categories of impaired fasting glucose (IFG ADA, IFG WHO) and impaired glucose tolerance (IGT) among 8498 Iranian participants in the Teheran Lipid and Glucose Study. When using the IFG ADA definition, prediabetic women had an increased risk of hypertension, whereas prediabetic men had an increased risk of chronic kidney disease (CKD). Women with IGT had an increased risk of coronary heart disease (CHD) and men classified by IFG WHO had an increased risk of stroke compared with normoglycaemic participants. Strikingly, the risk of stroke in prediabetic men was as strong as the risk of stroke in diabetic men, and CHD risk in prediabetic women was as strong as CHD risk in diabetic women. These associations did not differ after adjusting for potential confounders that included age, education level, smoking, medications, body mass index, lipid profile and family history of disease. The study confirms previous evidence suggesting an increased risk of CHD in women and an increased risk of stroke in men. If the results of Parizadeh et al. are replicated, IFG ADA could be useful to identify men at risk for CKD and women at risk for hypertension. IFG WHO could help to identify men at risk for stroke, and IGT could improve early identification of women at risk for CHD.