Research Paper|Volume 13, Issue 11|pp 14785—14805

Exacerbation of cardiovascular ageing by diabetes mellitus and its associations with acyl-carnitines

Fei Gao^1,², Jean-Paul Kovalik^2,³, Xiaodan Zhao¹, Vivian JM. Chow¹, Hannah Chew¹, Louis LY. Teo^1,², Ru San Tan^1,², Shuang Leng¹, See Hooi Ewe^1,², Hong Chang Tan^2,³, Tsze Yin Tan², Lye Siang Lee², Jianhong Ching^2,⁵, Bryan MH. Keng¹, Liang Zhong^1,², Woon-Puay Koh⁴, Angela S. Koh^1,²

¹National Heart Centre Singapore, Singapore
²Duke-NUS Medical School, Singapore
³Singapore General Hospital, Singapore
⁴Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
⁵KK Research Centre, KK Women's and Children's Hospital, Singapore

Received: January 26, 2021Accepted: May 17, 2021Published: June 4, 2021

https://doi.org/10.18632/aging.203144

Copyright: © 2021 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To demonstrate differences in cardiovascular structure and function between diabetic and non-diabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements.

Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination.

Results: A total of 933 participants (women 56%, n=521) with a mean age 63±13 years were studied. Old diabetics compared to old non-diabetics had lower myocardial relaxation (0.8±0.2 vs 0.9±0.3, p=0.0039); lower left atrial conduit strain (12±4.3 vs 14±4.1, p=0.045), lower left atrial conduit strain rate (-1.2±0.4 vs -1.3±0.5, p=0.042) and lower ratio of left atrial conduit strain to left atrial booster strain (0.5±0.2 vs 0.7±0.3, p=0.0029). Higher levels of archived short chain acyl-carnitine were associated with present-day impairments in myocardial relaxation (C5:1; OR 1.03, p=0.011), worse left atrial conduit strain function (C5:1; OR 1.03, p=0.037). Increases in hydroxylated acyl-carnitines were associated with worse left atrial conduit strain [(C4-OH; OR 1.05, p=0.0017), (C16:2-OH; OR 1.18, p=0.037)]. Current, archived and changes in long chain acyl-carnitines were associated with cardiovascular functions [(C16; OR 1.02, p=0.002), (C20:3; OR 1.01, p=0.014), (C14:3; OR 1.12, p=0.033), (C18:1; OR 1.01, p=0.018), (C18:2; OR 1.01, p=0.028), (C20:4; OR 1.10, p=0.038)] (all p<0.05).

Conclusion: Older diabetic adults had significant impairments in left ventricular myocardial relaxation and left atrial strain, compared to older non-diabetic adults. Short chain and long chain, di-carboxyl and hydroxylated acyl-carnitines were associated with these cardiovascular functional differences.