二甲双胍除了影响血糖水平外，其还会对影响血脂水平，近日一项刊登在国际杂志Diabetes Care上的研究论文中，来自德国糖尿病研究中心的研究人员就发现二甲双胍或许还会影响机体的血脂水平，尤其是可以使得有害的低密度脂蛋白胆固醇水平下降。
文章中研究者对加入德国大规模研究KORA的参与者进行了研究，分析了来自参与者的1800份血液样本，利用一种综合性的手段科学家们调查分析了参与者机体的代谢产物及参与者机体的遗传特性。结果显示，对2型糖尿病患者服用二甲双胍可以有效改变患者机体的代谢产物的水平，而二甲双胍的服用和患者机体低密度脂蛋白胆固醇的水平明显下降直接相关，低密度脂蛋白胆固醇被认为是引发动脉粥样硬化进而引发心血管疾病的风险因素。
研究者随后根据患者的遗传信息及代谢产物的浓度进行了综合的考虑和分析，鉴别出了参与各自调控途径的代谢物和基因；Rui Wang-Sattler教授说道，我们推测，二甲双胍的摄入会通过AMPK途径来影响低密度脂蛋白胆固醇的水平，从而导致基因FADS1和FADS2的表达被下调，研究者对三种依赖于FADS的脂质代谢物的研究也证实了上述结论，随后研究者将会去分析研究二甲双胍引发低密度脂蛋白胆固醇水平降低的机制。
研究者表示，二甲双胍或许对糖尿病患者患心血管疾病的确有一种额外的附加有益效应，截止到目前这种作用机制尚不清楚，但后期研究者将通过更多深入的研究来阐明二甲双胍如何降低糖尿病患者机体的低密度脂蛋白水平的。
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Effects of Metformin on metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes
Tao Xu1,2, Stefan Brandmaier1,2, Ana C. Messias3, Christian Herder4,5, Harmen H.M. Draisma6,7,8, Ayse Demirkan9,10, Zhonghao Yu1,2, Janina S. Ried11, Toomas Haller12, Margit Heier2, Monica Campillos13, Gisela Fobo13, Renee Stark14, Christina Holzapfel15, Jonathan Adam1,2, Shen Chi1,2, Markus Rotter1,2, Tommaso Panni2, Anne S. Quante11,16, Ying He17,18, Cornelia Prehn19, Werner Roemisch-Margl13, Gabi Kastenmüller13, Gonneke Willemsen6,7, René Pool6,7, Katarina Kasa9, Ko Willems van Dijk10, Thomas Hankemeier20, Christa Meisinger2, Barbara Thorand2, Andreas Ruepp13, Martin Hrabé de Angelis21,22,23, Yixue Li17,18, H.-Erich Wichmann2,16,24, Bernd Stratmann25, Konstantin Strauch11,16, Andres Metspalu12, Christian Gieger1,2, Karsten Suhre13,26,27, Jerzy Adamski19,22,23, Thomas Illig1,28,29, Wolfgang Rathmann30, Michael Roden4,5,31, Annette Peters1,2,23,32, Cornelia M. van Duijn8,33, Dorret I. Boomsma6,7, Thomas Meitinger34,35 and Rui Wang-Sattler1,2,23⇑
OBJECTIVE Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND METHODS We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. RESULTS We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years’ follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. ConCLUSIONS Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.