Duke-NUS Medical School, Singapore; Singapore General Hospital, Singapore.
National Heart Centre Singapore, Singapore.
J Mol Cell Cardiol. 2021 Sep;158:63-71. doi: 10.1016/j.yjmcc.2021.05.009. Epub 2021 May 24.
Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function.
In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination.
We studied a total of 515 participants (women 50%, n = 255) with a mean age 73 (SD = 4.3) years. Diabetics had higher alanine (562 vs 448, p < 0.0001), higher glutamate (107 vs 95, p = 0.016), higher proline (264 vs 231, p = 0.008) and lower arginine (107 vs 117, p = 0.043), lower citrulline (30 vs 38, p = 0.006) levels (μM) compared to non-diabetics. Over time, changes in amino acid profiles differentiated diabetic older adults from non-diabetic older adults, with greater accumulation of alanine (p = 0.002), proline (p = 0.008) and (non-significant) trend towards greater accumulation of glycine (p = 0.057) among the older diabetics compared to the older non-diabetics. However, independent of diabetes status, amino acids were associated with cardiovascular functions in ageing, [archived valine (p = 0.011), leucine (p = 0.011), archived isoleucine (p = 0.0006), archived serine (p = 0.008), archived glycine (p = 0.006) methionine (p = 0.003)] which were associated with impairments in E/A ratio.
Markers of branched chain amino acids and one ‑carbon metabolism pathways were associated with changes in cardiovascular function in older adults regardless of diabetes status. However, nitrogen handling pathways were specifically altered among older adults with diabetes. These findings broaden our understanding into specific amino acid pathways that may be altered between diabetic and non-diabetic older adults, and their relevance to cardiovascular function in ageing.
ClinicalTrials.gov Identifier: NCT02791139.
衰老和胰岛素抵抗状态，如糖尿病，常同时存在，并增加老年人心血管疾病发展的风险。在这里，我们研究了衰老和糖尿病之间氨基酸谱的代谢差异，及其与心血管功能的关系。
在一组社区老年人中，我们进行了超声心动图、心脏磁共振成像以及基于当前和 15 年前获得的存档血清进行的横断面和纵向代谢组学分析。
我们共研究了 515 名参与者（女性 50%，n=255），平均年龄 73（SD=4.3）岁。糖尿病患者的丙氨酸（562 比 448，p<0.0001）、谷氨酸（107 比 95，p=0.016）、脯氨酸（264 比 231，p=0.008）和精氨酸（107 比 117，p=0.043）水平较高，瓜氨酸（30 比 38，p=0.006）水平较低（μM）。随着时间的推移，氨基酸谱的变化将糖尿病老年人与非糖尿病老年人区分开来，糖尿病老年人的丙氨酸（p=0.002）、脯氨酸（p=0.008）和（非显著）甘氨酸积累趋势较大（p=0.057）。然而，独立于糖尿病状态，氨基酸与衰老过程中心血管功能有关，[存档缬氨酸（p=0.011）、亮氨酸（p=0.011）、存档异亮氨酸（p=0.0006）、存档丝氨酸（p=0.008）、存档甘氨酸（p=0.006）、蛋氨酸（p=0.003）]与 E/A 比值的损害有关。
支链氨基酸和一碳代谢途径的标志物与老年人心血管功能的变化有关，无论糖尿病状态如何。然而，氮处理途径在患有糖尿病的老年人中特异性改变。这些发现拓宽了我们对糖尿病和非糖尿病老年人之间可能改变的特定氨基酸途径的理解，以及它们与衰老中心血管功能的关系。
ClinicalTrials.gov 标识符：NCT02791139。
