Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Front Endocrinol (Lausanne). 2022 Nov 17;13:1009095. doi: 10.3389/fendo.2022.1009095. eCollection 2022.
Hyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management.
We tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes.
Traditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72-0.97, ) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes ().
We verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.
高脂血症传统上被认为是糖尿病的一个危险因素。低密度脂蛋白胆固醇（LDL-C）对糖尿病的影响与直觉相反。我们试图研究 LDL-C 与糖尿病之间的关系，以更好地进行血脂管理。
我们检验了 LDL-C 与糖尿病之间的关联形式，并构建了 LDL-C 的多基因风险评分，并生成了 LDL-C 与糖尿病之间的线性孟德尔随机化（MR）估计值。我们评估了 LDL-C 与糖尿病之间观察性和遗传关系中的非线性。
传统的观察性分析表明，LDL-C 与糖尿病之间存在复杂的非线性关联，而非线性 MR 分析则没有发现这种关联是非线性的证据。在线性关联的假设下，我们发现 LDL-C 对未使用降脂药物的女性糖尿病具有一致的保护作用。在观察性分析中，OR 值为 0.84（95%CI，0.72-0.97，），MR 分析中的结果更显著，表明增加女性 LDL-C 的总体分布会降低糖尿病的总体风险（）。
我们验证了未使用降脂药物的女性中 LDL-C 对糖尿病的线性保护作用。观察性分析中 LDL-C 对糖尿病的非线性关联不是因果关系。
