CAPHRI School for Public Health and Primary Care.
NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University.
J Hypertens. 2019 Feb;37(2):365-371. doi: 10.1097/HJH.0000000000001892.
Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)].
We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ± 7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness.
Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient.
We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.
2 型糖尿病（T2D）与心肌梗死和中风等心血管疾病并发症有关。这些并发症至少部分是由于糖尿病相关的动脉僵硬增加所致。二甲双胍是一种首选的口服降血糖药物，与潜在的心脏保护作用有关。然而，目前尚无关于真实生活中使用二甲双胍与动脉僵硬之间关联的相关数据。本研究的目的是在 T2D 患者的人群中，研究真实生活中使用二甲双胍与主动脉僵硬（即颈动脉-股动脉脉搏波速度，cfPWV）和颈动脉僵硬[即颈动脉扩张系数和杨氏弹性模量（YEM）]之间的关联。
我们使用了 Maastricht 研究的数据，这是一项正在进行的观察性前瞻性人群队列研究（目前的 N=3451）。所有基于药房记录的 T2D 患者（N=672，31.3%为女性，平均年龄 62.6±7.7）均纳入本研究。线性回归分析用于研究与无二甲双胍使用相比，当前二甲双胍使用与 cfPWV、扩张系数和 YEM 之间的关联。此外，根据累积剂量（克）、使用持续时间（天）、平均日剂量（克）和首次处方后时间（年）对二甲双胍使用进行分层。扩张系数的回归系数乘以-1，因此，对于所有动脉僵硬指标，正回归系数表示动脉僵硬增加。
线性回归显示，当前二甲双胍使用与 cfPWV 无关[调整后的 B：-0.04（-0.11 至 0.02）]，也与累积剂量、使用持续时间、平均日剂量或首次处方后时间的分层无关。二甲双胍的使用与颈动脉弹性的评估指标扩张系数显著相关（0.12（0.01 至 0.23）），但与 YEM 无关（0.10（-0.03 至 0.22））。然而，当进一步研究与扩张系数的关联时，没有发现不同的二甲双胍使用分层之间存在一致的模式。
我们表明，无论如何定义二甲双胍的使用，当前二甲双胍的使用与主动脉僵硬之间没有显著关联。此外，二甲双胍的使用与颈动脉僵硬程度降低无关。本研究结果表明，在中年 T2D 患者中，二甲双胍的使用、剂量或持续时间对动脉僵硬没有有益的影响。或者，二甲双胍可能通过其他途径发挥其心脏保护作用。
