152-OR: Sex Differences in Metabolomics and Risk of Coronary Heart Disease in Type 2 Diabetes

Aim: We compared circulating metabolites and their associations with coronary heart disease (CHD) in men and women across glycemic status. Method: We used metabolomic data (amino acids, glycolysis, ketone bodies, inflammation, fluid balance, fatty acids, lipids, lipoproteins) for 95,108 CHD-free UK Biobank participants. We used linear regressions to examine the association of sex and metabolites (log) in newly diagnosed T2D (diagnosis2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia, accounting for age, race, Deprivation Index, income, smoking, obesity, medications for hypertension, hyperlipidemia .05), particularly in T2D (ptrend.05). Men had higher creatinine and albumin across glycemic levels (ptrend.05). In a 10-year follow-up, an SD higher GlycA (W HR 16.1, 95%CI 2.1-137.8 vs M 0.5, 0.1-1.7), SFA (W 4.5, 1.5-13.8 vs M 0.9, 0.5-2.8), triglycerides (TG)/phosphoglycerids ratio (W 3.0, 1.4-6.8 vs M 1.3, 0.7-2.3), and total TG (W 2.5, 1.3-4.9 vs M 1.1, 0.7-1.7) was associated with CHD risk in women with T2D, but not in men (p-interaction.1). Conclusions: With advancing glycemic status, women had higher levels of markers of inflammation, fatty acids, and atherogenic lipids, while men had higher levels of renal markers. Women with T2D are at a higher risk of CHD associated with GlycA, SFA, and TG than men with T2D. Disclosure Y. Yoshida: None. D. Li: None. X. Li: None. V. Fonseca: Consultant; Abbott, Bayer Inc. Stock/Shareholder; BRAVO4HEALTH, LLC. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Research Support; Fractyl Health, Inc. Consultant; Sun Pharmaceutical Industries Ltd. Stock/Shareholder; Amgen Inc. F. Mauvais-Jarvis: None. L. Qi: None. Funding American Diabetes Association (7-23-JDFWH-10)