Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy.
Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy.
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DOI：
10.1186/s12933-021-01353-z
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发表时间：
2021-08-03
影响因子：
9.3
通讯作者：
Shah SH
中科院分区：
文献类型：
--
作者：
Truby LK;Regan JA;Giamberardino SN;Ilkayeva O;Bain J;Newgard CB;O'Connor CM;Felker GM;Kraus WE;McGarrah RW;Shah SH
心力衰竭(HF)合并糖尿病(DM)患者与不合并糖尿病(DM)的心力衰竭(HF)患者是否存在循环长链酰肉碱(LCAC)的差异，以及这些生物标志物是否报告运动能力和临床结果，尚不清楚。本研究的目的是利用代谢组学来确定报告运动能力、临床结果和运动对运动的不同反应的生物标记物。采用靶向质谱仪对心力衰竭患者血浆中的代谢物进行量化：一项调查运动训练(HF-ACTION)试验结果的对照试验。通过主成分分析确定了12个不相关因素。评估代谢因素、糖尿病状况、运动量和时间与全因死亡或全因住院的主要临床结果之间的关系。共纳入664名参与者：359名(54%)患有糖尿病。LCAC因子水平与以最大耗氧量衡量的基线运动能力(β0.86，p = 2 × 10−7)相关，且在有和不伴有DM的参与者中存在差异(p分别为1.58，p = 8 × 10−8 vs.0.67，p = 9 × 10−4；p值为相互作用 = 0.012)。糖尿病患者运动后LCAC水平的变化(平均∆为0.09，p = 为0.24)小于非糖尿病患者(平均∆为0.16，p = 为0.08)。在单变量和多变量模型中，LCAC因子水平与到达主要预后的时间相关(多变量HR0.80，p = 2.74 × 10−8)，并且与糖尿病参与者的预后关系更强(HR0.64，p = 3.21 × 10−9vs.HR 0.90，p = 0.104，交互作用 = 0.001的p值)。当在个体代谢物水平上进行分析时，C16、C16：1、C18和C18：1与运动能力和结果的相关性最大，水平越高，结果越差。在导管术遗传学研究(CATHGEN)中未发现心衰患者的对照组中，没有发现与主要临床结果的时间相关的类似关系。LCAC生物标志物与运动状态和临床结果在合并和不合并糖尿病的心衰患者中有不同的关联。脂肪酸底物利用受损和骨骼肌和心肌水平的线粒体功能障碍可能解释了运动能力下降、对运动训练的反应减弱以及心力衰竭和糖尿病患者不良的临床结果。临床试验注册.gov标识：NCT00047437。网上版载有补充材料，可在10.1186/s12933-021-01353-z查阅。
Whether differences in circulating long chain acylcarnitines (LCAC) are seen in heart failure (HF) patients with and without diabetes mellitus (DM), and whether these biomarkers report on exercise capacity and clinical outcomes, remains unknown. The objective of the current study was to use metabolomic profiling to identify biomarkers that report on exercise capacity, clinical outcomes, and differential response to exercise in HF patients with and without DM. Targeted mass spectrometry was used to quantify metabolites in plasma from participants in the heart failure: a controlled trial investigating outcomes of exercise training (HF-ACTION) trial. Principal components analysis was used to identify 12 uncorrelated factors. The association between metabolite factors, diabetes status, exercise capacity, and time to the primary clinical outcome of all-cause mortality or all-cause hospitalization was assessed. A total of 664 participants were included: 359 (54%) with DM. LCAC factor levels were associated with baseline exercise capacity as measured by peak oxygen consumption (beta 0.86, p = 2 × 10−7, and were differentially associated in participants with and without DM (beta 1.58, p = 8 × 10−8 vs. 0.67, p = 9 × 10−4, respectively; p value for interaction = 0.012). LCAC levels changed to a lesser extent in participants with DM after exercise (mean ∆ 0.09, p = 0.24) than in those without DM (mean ∆ 0.16, p = 0.08). In univariate and multivariate modeling, LCAC factor levels were associated with time to the primary outcome (multivariate HR 0.80, p = 2.74 × 10−8), and were more strongly linked to outcomes in diabetic participants (HR 0.64, p = 3.21 × 10−9 v. HR 0.90, p = 0.104, p value for interaction = 0.001). When analysis was performed at the level of individual metabolites, C16, C16:1, C18, and C18:1 had the greatest associations with both exercise capacity and outcomes, with higher levels associated with worse outcomes. Similar associations with time to the primary clinical outcome were not found in a control group of patients without HF from the CATHeterization GENetics (CATHGEN) study. LCAC biomarkers are associated with exercise status and clinical outcomes differentially in HF patients with and without DM. Impaired fatty acid substrate utilization and mitochondrial dysfunction both at the level of the skeletal muscle and the myocardium may explain the decreased exercise capacity, attenuated response to exercise training, and poor clinical outcomes seen in patients with HF and DM. Trial Registration clinicaltrials.gov Identifier: NCT00047437. The online version contains supplementary material available at 10.1186/s12933-021-01353-z.
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影响因子：
37.8
作者：
Shah SH;Kraus WE;Newgard CB
通讯作者：
Newgard CB
影响因子：
4.2
作者：
POLLITT, RJ
通讯作者：
POLLITT, RJ
影响因子：
8.2
作者：
Ouwens, D. M.;Diamant, M.;Fodor, M.;Habets, D. D. J.;Pelsers, M. M. A. L.;El Hasnaoui, M.;Dang, Z. C.;van den Brom, C. E.;Vlasblom, R.;Rietdijk, A.;Boer, C.;Coort, S. L. M.;Glatz, J. F. C.;Luiken, J. J. F. P.
通讯作者：
Luiken, J. J. F. P.
影响因子：
7.7
作者：
Luiken, JJFP;Koonen, DPY;Glatz, JFC
通讯作者：
Glatz, JFC
DOI：
10.1152/ajpendo.00656.2013
发表时间：
2014-06-15
影响因子：
5.1
作者：
Rutkowsky, Jennifer M.;Knotts, Trina A.;Hwang, Daniel H.
通讯作者：
Hwang, Daniel H.