Abstract：
OBJECTIVE: Recent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment.
RESULTS: This study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034-1.109, P = 1.36 × 10-4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028-1.077, P = 1.80 × 10-5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108-1.243, P = 4.65 × 10-8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892-0.966, P = 2.37 × 10-4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897-0.967, P = 2.37 × 10-4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812-0.935, P = 1.24 × 10-4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified.
CONCLUSIONS: This MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.
RESULTS: This study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034-1.109, P = 1.36 × 10-4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028-1.077, P = 1.80 × 10-5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108-1.243, P = 4.65 × 10-8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892-0.966, P = 2.37 × 10-4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897-0.967, P = 2.37 × 10-4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812-0.935, P = 1.24 × 10-4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified.
CONCLUSIONS: This MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM.
摘要：
目的：最近的研究扩展了我们对血浆脂质种类的认识，建立在血脂水平与2型糖尿病（T2DM）风险之间的既定联系。确定这些脂质种类的因果作用是改善T2DM风险评估的关键。
结果：本研究采用孟德尔随机化（MR）研究13种脂质类别的179种脂质与T2DM之间的因果关系。摘要水平数据来自全基因组关联研究。主要的分析方法包括逆方差加权(IVW)方法和Wald比率，辅以一系列敏感性分析，以确保结果的稳健性。IVW分析揭示了神经酰胺水平升高（d40：2）之间存在显着因果关系（OR=1.071，95％CI1.034-1.109，P=1.36×10-4），鞘磷脂(d38:1)(OR=1.052,95%CI1.028-1.077,P=1.80×10-5),和三酰甘油（56：8）（OR=1.174，95％CI1.108-1.243，P=4.65×10-8），和T2DM的风险增加。相反，Wald比值分析表明磷脂酰胆碱(O-16:1_16:0)水平较高(OR=0.928,95%CI0.892-0.966,P=2.37×10-4),磷脂酰胆碱(O-16:1_20:4)(OR=0.932,95%CI0.897-0.967,P=2.37×10-4),磷脂酰胆碱（O-18：2_20：4）（OR=0.872，95％CI0.812-0.935，P=1.24×10-4）与T2DM风险降低显着相关。此外，确定了另外22种脂质的暗示性因果证据.
结论：这项MR研究建立了调节T2DM风险的特定脂质类别之间的因果关系。它为T2DM的风险评估和潜在治疗目标提供了新的见解。
结果：本研究采用孟德尔随机化（MR）研究13种脂质类别的179种脂质与T2DM之间的因果关系。摘要水平数据来自全基因组关联研究。主要的分析方法包括逆方差加权(IVW)方法和Wald比率，辅以一系列敏感性分析，以确保结果的稳健性。IVW分析揭示了神经酰胺水平升高（d40：2）之间存在显着因果关系（OR=1.071，95％CI1.034-1.109，P=1.36×10-4），鞘磷脂(d38:1)(OR=1.052,95%CI1.028-1.077,P=1.80×10-5),和三酰甘油（56：8）（OR=1.174，95％CI1.108-1.243，P=4.65×10-8），和T2DM的风险增加。相反，Wald比值分析表明磷脂酰胆碱(O-16:1_16:0)水平较高(OR=0.928,95%CI0.892-0.966,P=2.37×10-4),磷脂酰胆碱(O-16:1_20:4)(OR=0.932,95%CI0.897-0.967,P=2.37×10-4),磷脂酰胆碱（O-18：2_20：4）（OR=0.872，95％CI0.812-0.935，P=1.24×10-4）与T2DM风险降低显着相关。此外，确定了另外22种脂质的暗示性因果证据.
结论：这项MR研究建立了调节T2DM风险的特定脂质类别之间的因果关系。它为T2DM的风险评估和潜在治疗目标提供了新的见解。
