Yoshida Yilin, Li Danting, Li Xiang, Fonseca Vivian A, Qi Lu, Mauvais-Jarvis Franck
Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
medRxiv. 2024 Jul 24:2024.07.23.24310540. doi: 10.1101/2024.07.23.24310540.
Women with type 2 diabetes (T2D) have a 50% excess risk of coronary heart disease (CHD) than men with T2D. We compared circulating metabolites and their associations with CHD in men and women across glycemic status.
We used metabolomic data (lipoproteins, fatty acids, amino acids, glycolysis, ketones, inflammation, and fluid balance) for 87,326 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, alcohol drinking, obesity, physical activity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox models to evaluate the association of metabolites and CHD risk by sex, adjusting the same covariates and menopausal status (women). All analyses were FDR-adjusted.
We included 1250 individuals with new T2D, 12,706 with prediabetes, and 83,315 with euglycemia. In adjusted linear regressions, women showed a progressive increase in atherogenic lipid and lipoprotein markers and inflammatory marker, glycoprotein acetyls, compared to men as their glycemic status advanced. However, women had lower levels of albumin during this transition. Menopausal status did not alter these sex differences. In a 10-year follow-up, an SD higher total TG, TG in VLDL, LDL, and HDL, saturated fatty acids (SFA) were positively associated with a higher risk of CHD in women with T2D but not in men (p-interactions 0.03-0.15).
With advancing glycemic status, women exhibited higher levels of atherogenic lipids and lipoproteins, as well as inflammatory markers, but lower circulating albumin. Women with T2D appear to be at a higher risk of CHD associated with TG, VLDL-TG, LDL-TG, and HDL-TG, and SFA than men with T2D.
2型糖尿病（T2D）女性患冠心病（CHD）的风险比T2D男性高50%。我们比较了不同血糖状态下男性和女性的循环代谢物及其与冠心病的关联。
我们使用了来自87326名无冠心病的英国生物银行参与者的代谢组学数据（脂蛋白、脂肪酸、氨基酸、糖酵解、酮类、炎症和体液平衡）。我们使用线性回归来研究新诊断的T2D（诊断时间距基线<2年）、糖尿病前期（糖化血红蛋白A1c为5.7 - 6.5%）和血糖正常状态下性别与代谢物（对数形式）之间的关联，并对年龄、种族、贫困指数、收入、吸烟、饮酒、肥胖、身体活动、高血压、高脂血症和糖尿病用药等因素进行了校正。我们使用Cox模型来评估按性别划分的代谢物与冠心病风险之间的关联，并对相同的协变量和绝经状态（女性）进行了校正。所有分析均进行了错误发现率（FDR）校正。
我们纳入了1250名新诊断的T2D患者、12706名糖尿病前期患者和83315名血糖正常者。在调整后的线性回归中，随着血糖状态的进展，与男性相比，女性的致动脉粥样硬化脂质和脂蛋白标志物以及炎症标志物糖蛋白乙酰化物呈逐渐上升趋势。然而，在此转变过程中女性的白蛋白水平较低。绝经状态并未改变这些性别差异。在10年的随访中，标准差较高的总甘油三酯（TG）、极低密度脂蛋白（VLDL）中的TG、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）中的TG以及饱和脂肪酸（SFA）与T2D女性患冠心病的较高风险呈正相关，但与男性无关（p交互作用为0.03 - 0.15）。
随着血糖状态的进展，女性表现出更高水平的致动脉粥样硬化脂质和脂蛋白以及炎症标志物，但循环白蛋白水平较低。与T2D男性相比，T2D女性似乎因TG、VLDL - TG、LDL - TG、HDL - TG和SFA而患冠心病的风险更高。
