440-P: Influence of Sex on the Association between Vascular Endothelial Dysfunction and Plasma Leptin Levels in People with Type 2 Diabetes

Evidence from basic studies indicates that leptin, a key hormone in the regulation of food intake and energy expenditure, induces endothelium-dependent vasorelaxation. It is well known that plasma leptin levels of women are higher than those of men, however, the influence of sex on the relationship between vascular function and leptin remains unclear. In this study, we investigated the influence of sex on the relationship between plasma leptin levels and vascular endothelial dysfunction in people with type 2 diabetes (T2D). We included 337 Japanese people (195 men and 142 women) with T2D in this study. We measured flow-mediated dilatation (FMD) of the brachial artery to evaluate vascular endothelial function. Compared to women, men had lower leptin levels (the medians 2.6 vs. 7.6 ng/mL, p < 0.001) and lower FMD (the medians 5.6 vs. 6.4%, p = 0.044). Multivariate analysis revealed that plasma leptin levels in men were positively associated with FMD (β = 0.184, p = 0.034) independently of classical cardiovascular risk factors, such as age, BMI, HbA1c, eGFR, and serum phosphate levels. On the other hand, no association was found between serum leptin levels and FMD in women (β = 0.046, p = 0.662). Higher BMI and higher systolic blood pressure also showed an independent association with lower FMD in men, while only older age did in women. These data showed that there are sex differences in factors associated with FMD in people with T2D, and plasma leptin level is one of them. Considering the vasodilatory effect of leptin itself, this study suggests a functional relationship between low plasma leptin levels and vascular endothelial dysfunction in men with T2D.