Background

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.

Methods

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.

Results

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.

Conclusion

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.

Trial registration: ClinicalTrials.gov Identifier: NCT02791139

中文翻译：

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糖尿病老年人与非糖尿病老年人的氨基酸差异及其与心血管功能的关系

背景

衰老和糖尿病等胰岛素抵抗状态经常共存并增加老年人患心血管疾病的风险。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，以及它们与心血管功能的关系。

方法

在一组社区老年人中，我们根据检查前十五年获得的当前和存档血清进行了超声心动图、心脏磁共振成像以及横截面和纵向代谢组学分析。

结果

我们共研究了 515 名参与者（女性 50%，n  = 255），平均年龄为 73 (SD = 4.3) 岁。糖尿病患者的丙氨酸含量较高（562 vs 448，p  < 0.0001），谷氨酸含量较高（107 vs 95，p  = 0.016），脯氨酸含量较高（264 vs 231，p  = 0.008），精氨酸含量较低（107 vs 117，p  = 0.043）， 与非糖尿病患者相比，瓜氨酸（30 对 38，p = 0.006）水平（μM）较低。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，丙氨酸（p  = 0.002）、脯氨酸（p  = 0.008）和（不显着）甘氨酸积累更多的趋势（p = 0.057) 与老年非糖尿病患者相比，老年糖尿病患者。然而，与糖尿病状态无关，氨基酸与衰老中的心血管功能相关，[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 比率的损害有关。

结论

无论糖尿病状态如何，支链氨基酸和单碳代谢途径的标志物都与老年人心血管功能的变化相关。然而，在患有糖尿病的老年人中，氮处理途径发生了特别的改变。这些发现拓宽了我们对可能在糖尿病和非糖尿病老年人之间改变的特定氨基酸途径的理解，以及它们与衰老过程中心血管功能的相关性。

试验注册：ClinicalTrials.gov 标识符：NCT02791139