Abstract P162: Sex Differences in Cardiometabolic Biomarkers During Pre-Diabetes

Abstract

Background: Diabetes (DM) diminishes female protection against cardiovascular disease (CVD). Women with DM face excess CVD risk than men partly due to women’s greater deterioration in risk factors before DM. In this study, we compared sex differences in biomarkers that reflect distinct pathophysiological pathways during the pre-diabetes (pre-DM) stage. Method: A cross-sectional analysis was performed based on pooled data from Atherosclerosis Risk in Communities Study and the Jackson Heart Study. We used multivariable linear regressions to examine the associations between sex and biomarkers (log-transformed) representative of inflammation, lipoprotein, adipokine, kidney function, cardiac injury/stress, and thrombosis, adjusted for age, race, and BMI, among CVD-free individuals with pre-DM. We validated the results in a sensitivity analysis, including those that eventually progressed into DM during the follow-up. We used the false discovery rate method to adjust multiple comparisons. Results: Among 5975 individuals with pre-DM, the mean age was 54.2 years, 2853 (48%) were women, and 2022 (34%) were non-Hispanic blacks. In the adjusted models, inflammatory biomarkers, including high-sensitivity c-reactive proteins (β coefficient 0.2, P=2.9 x 10 -9 ), fibrinogen (β 0.19, P=2.8E-12), and absolute lymphocyte (β 0.25, P=2.54 x 10 -7 ), and cardiac injury/stress biomarker, NT-proBNT (β 0.14, P=0.0002) were higher in women than men with pre-DM. Additionally, lipoprotein(a) (β 0.19, P=4.96 x 10 -13 ) and apolipoproteins A1 (β 0.61, P=2.81x 10 -120 ), and adipokines including leptin (β 1.1, P=2.62 x 10 -123 ) and adiponectin (β 0.56, P=1.94 x 10 -12 ) were all higher in women with pre-DM. In contrast, kidney function markers, albumin (β -0.24, P=2.79 x 10 -9 ) and creatinine (β -1.1, P=1x 10 -100 ), and thrombosis biomarker, homocysteine (β -0.5, P=9.09 x 10 -19 ) were higher in men with pre-DM than in their women counterparts. These sex differences remained generally unchanged among 2320 individuals that progressed into DM. Conclusion: Biomarkers differ significantly between sexes during the pre-DM state. The inflammatory, lipoprotein, adipokine, and cardiac stress biomarkers were higher in women with pre-DM, while kidney function and thrombosis biomarkers were higher in men with pre-DM. Future mechanistic studies are warranted to delineate pathophysiological pathways characterized by these biomarkers contributing to sex disparities of CVD risk in DM.