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

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.