Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank.
Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank.
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DOI：
10.1161/circresaha.122.320796
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发表时间：
2022-09-02
影响因子：
20.1
通讯作者：
Chirinos JA
中科院分区：
文献类型：
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作者：
Cohen JB;Mitchell GF;Gill D;Burgess S;Rahman M;Hanff TC;Ramachandran VS;Mutalik KM;Townsend RR;Chirinos JA
胰腺、肝脏和骨骼肌中大动脉僵硬（LAS）引起的微血管损伤可能影响葡萄糖稳态。我们的目标是通过前瞻性收集的、仔细分型的LAS测量值以及孟德尔随机化分析来评估LAS与2型糖尿病风险之间的关系。对5,676名无糖尿病的FHS参与者进行了颈动脉-股动脉脉搏波速度（CF-PWV）、肱动脉和中心脉压的测量。我们使用考克斯比例风险回归来评估CF-PWV和脉压与糖尿病发病的关系。我们随后进行了两个样本的孟德尔随机化分析，评估英国生物库（UKBB）中遗传预测的肱动脉脉压与2型糖尿病的相关性。在FHS中，CF-PWV较高的个体年龄较大，男性较多，与CF-PWV较低的个体相比，其体重指数和平均动脉压较高。在中位随访7年后，CF-PWV和中心脉压与新发糖尿病的风险增加相关（根据标准差增加，多变量调整的CF-PWV风险比[aHR] aHR 1.36，95%置信区间[CI] 1.03-1.76，P=0.030;中心脉压aHR 1.26，95%CI 1.08-1.48，P=0.004）。在UKBB研究中，基因预测的肱动脉脉压与2型糖尿病相关，与平均动脉压无关（调整后的比值比1.16，95% CI：1.00-1.35，P=0.049）。使用前瞻性队列数据结合孟德尔随机化分析，我们发现证据支持更大的LAS与发生糖尿病的风险增加相关。LAS可能在葡萄糖稳态中发挥重要作用，并可能作为未来糖尿病风险的有用标志物。
Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscle may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes mellitus using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses. Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5,676 participants of the Framingham Heart Study (FHS) without diabetes mellitus. We used Cox proportional hazards regression to evaluate the association of CF-PWV and pulse pressure with incident diabetes mellitus. We subsequently performed two-sample Mendelian randomization analyses evaluating the associations of genetically-predicted brachial pulse pressure with type 2 diabetes mellitus in the United Kingdom Biobank (UKBB). In FHS, individuals with higher CF-PWV were older, more often male, and had higher body mass index and mean arterial pressure compared to those with lower CF-PWV. After a median follow-up of 7 years, CF-PWV and central pulse pressure were associated with an increased risk of new-onset diabetes mellitus (per standard deviation increase, multivariable-adjusted CF-PWV hazard ratio [aHR] aHR 1.36, 95% confidence interval [CI] 1.03-1.76, P=0.030; central pulse pressure aHR 1.26, 95% CI 1.08-1.48, P=0.004). In UKBB, genetically-predicted brachial pulse pressure was associated with type 2 diabetes mellitus, independent of mean arterial pressure (adjusted odds ratio 1.16, 95% CI: 1.00-1.35, P=0.049). Using prospective cohort data coupled with Mendelian randomization analyses, we found evidence supporting that greater LAS is associated with increased risk of developing diabetes. LAS may play an important role in glucose homeostasis and may serve as a useful marker of future diabetes risk.