1225-P: Biomarkers in Prediabetes Reflecting Sex Varying Pathways of Cardiovascular Risk

Abstract

Background: Women with diabetes (DM) had higher cardiovascular risk than men, partly due to women’s higher cardiometabolic risk factors before DM. We compared sex differences in biomarkers that reflect distinct pathophysiological pathways in prediabetes (PreDM). Method: We conducted a cross-sectional analysis of similarly designed Atherosclerosis Risk in Communities Study and the Jackson Heart Study. We used multivariable linear regressions for the associations between sex and biomarkers (log(x)) representative of inflammation, cardiac injury/stress, lipoprotein, adipokine, kidney function, and glycemia adjusted for age, race, BMI, blood pressure, total cholesterol, smoking, hypertensive meds, and statins in CVD-free individuals with PreDM. We evaluated the effect modification of menopause and validated results in those who progressed into DM in follow-up. False discovery rate adjusted multiple comparisons. Results: In 5765 people with PreDM at baseline, the mean age was 54 y, 47% women, and 35% non-Hispanic Blacks. Inflammatory c-reactive protein (β coefficient 0.3 P=5×10-51), fibrinogen (β 0.2 P=3×10-12), and lymphocyte count (β 0.2 P=7×10-8), and cardiac NT-proBNT (β 0.6 P=1×10-104) were higher in women than men with PreDM. Lipoprotein(a) (β 0.2 P=1×10-10) and apolipoproteins A1 (Apo A1) (β 0.6 P=5 x 10-115), and adipokines, leptin (β 1.1 P=3×10-112) and adiponectin (β 0.6 P=6×10-16) were higher in women. Men with PreDM had higher random urinary creatinine (β -0.6 P=2×10-61) and reduced eGFR (β 0.3 P=5×10-29). They also had higher inflammatory homocysteine (β -0.5 P=2×10-12), triglycerides (β -0.2 P<.0001), and Apo B (β -0.1 P<.0001). Fructosamine, glycated albumin, and HbA1c did not differ by sex in PreDM. Menopause modifies sex differences in LDL-c, Apo B, and fibrinogen. Results were generally unchanged in people who later became DM. Conclusion: Overall, in PreDM, women had higher vascular inflammatory markers and adipokines, while men had higher kidney dysfunction markers. Disclosure Y.Yoshida: None. Z.Chen: None. C.Li: None. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. F.Mauvais-jarvis: None. Funding National Institutes of Health (K12HD043451)