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 (diagnosis<2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia, accounting for age, race, Deprivation Index, income, smoking, obesity, medications for hypertension, hyperlipidemia & diabetes. We used Cox models to evaluate the association of metabolites and CHD risk by sex, adjusting the same covariates & menopausal status. All analyses were FDR-adjusted.

Results: We included 1328 individuals with new T2D, 6204 with prediabetes, and 87,576 with euglycemia. In adjusted linear regressions, glycoprotein acetyls (GlycA, inflammation), fatty acids (total, polyunsaturated, saturated fatty acids [SFA]), lipids (phosphoglycerides, cholines, sphingomyelins, phospholipids), atherogenic lipoproteins (total cholesterol, non-HDL-c, remnant-c, LDL-c, cholesteryl esters, ApoB) were higher in women than in men across glycemic status (p_interaction<.05), particularly in T2D (p_trend<.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.