6719 Sex Differences In Lipoproteins And Excess Risk Of Coronary Heart Disease In Women With Type 2 Diabetes

Abstract Disclosure: Y. Yoshida: None. D. Li: None. X. Li: None. V.A. Fonseca: None. L. Qi: None. F. Mauvais-Jarvis: None. Background: Women with type 2 diabetes (T2D) have a greater risk of coronary heart disease (CHD) than men with T2D. We compared levels of lipoproteins and their associations with CHD in women and men with new-onset T2D, pre-diabetes (PDM), and euglycemia. Method: We obtained circulating metabolomic data, including lipoprotein classes, apolipoproteins, total triglycerides (TG), and TG in very large LDL (VLDL), LDL, and HDL by nuclear magnetic resonance for 95,108 CHD-free people at baseline and incident CHD from the national health registers of the UK Biobank study. We used multivariable linear regressions to examine the association between sex and lipoprotein markers (log(x)) in groups of new-onset T2D (new T2D diagnosis or diabetes medication use within two years from the baseline), PDM (HbA1c 5.7-6.5%), and euglycemia, accounting for age, race, Townsend Deprivation Index, income, smoking, obesity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox proportional hazard models to evaluate the association between lipoproteins and CHD risk in men and women separately, adjusting the same covariates. We performed sensitivity analyses using the assay-measured lipoproteins of the same participants and accounted for menopausal status. False discovery rate adjusted for multiple comparisons. Results: 1328 individuals with newly diagnosed T2D, 6204 with PDM, and 87,576 with euglycemia were included in the analysis. In adjusted linear regressions, atherogenic lipoproteins, including total cholesterol (c), non-HDL-c, remnant-c, and LDL-c were significantly higher in women than in men across glycemic status, and this sex difference was the most striking in the T2D group (β 0.5, 0.3, 0.15, and 0.23 in T2D vs. 0.44, 0.16, 0.09, and 0.12 in PDM vs. 0.37, 0.08, 0.04, and 0.08 in euglycemia). In euglycemic individuals, levels of Apo B and VLDL were higher in men than in women (β -0.01 and -0.05); however, in T2D individuals, women had higher levels of VLDL(β 0.05 and 0.05). Total TG and TG in VLDL were significantly higher in men with euglycemia (β -0.22 and -0.23) and PDM (β -0.15 and -0.16), but the sex differences were not significant in the T2D group (β -0.01 and -0.04). During the median 10-year follow-up, one SD increase in total TG (women HR 2.5, 95% 1.3-4.9 vs. men 1.07, 0.7-1.7 P-interaction=0.03), TG in VLDL (W 2.1, 1.2-3.7 vs. M 1.06 0.7-1.6 P=0.03), TG in LDL (W 3.2, 1.2-8.8 vs. M 1.3, 0.7-2.6, P=0.1), and TG in HDL (W 3.7, 1.4-9.5 vs. M 0.9, 0.5-1.7, P=0.008) was significantly associated with increased risk of CHD in women with T2D, but the associations were not significant in male patients. Results from available assay-measured markers and menopausal stratification were generally consistent with the main results. Conclusions: Women had higher levels of atherogenic lipids than men with advancing glycemic status. Women with T2D are at a higher risk of CHD associated with TG than men with T2D. Presentation: 6/3/2024