Introduction and Objective: Cardiovascular disease (CVD) is not well-studied in older people with long-duration Type 1 diabetes (T1D). In the Joslin “Medalists”, with T1D≥50 years, we assessed imaging and plasma metabolomic changes that may be associated with CVD, compared to Type 2 diabetes (T2D). Methods: Medalists were evaluated for self-reported CVD (n=1043), with subsets undergoing coronary artery calcium (CAC; n=159) and cardiac magnetic resonance (CMR; n=111) imaging, including stress and gadolinium studies. Plasma metabolomics were done in a Medalist subset (n=701), including those without baseline CVD (n=309) who were followed for CVD development. Metabolomics results were adjusted for false discovery rate (FDR0.05), age, sex, and eGFR. Results: In the overall Medalist cohort, 402 (40%) had CVD. Of those without baseline CVD, 85 (27.5%) developed CVD after a median follow-up of 6.9 years. 87% of Medalists had CAC100, compared to 65% and 35% in the T2D Diabetes Heart Study and MESA, respectively. In those without CVD, CMR showed greater focal perfusion abnormality (24% vs. 0, p=0.04) and lower myocardial perfusion ratio (1.28 vs. 1.70, p=0.01) in Medalists compared to T2D. Metabolomics revealed that pyruvate, alpha-ketobutyrate, and sarcosine all promoted oxidative phosphorylation, energy production, and protected against CVD development in Medalists. However, beta D-glucuronide and gulonate in the pentose and glucoronate shunt pathway increased CVD risk. These results differed from the T2D ADVANCE study (n=3587), which showed increased phenylalanine and decreased histidine being associated with CVD. Conclusion: Comparing CVD imaging and metabolomics between T1D and T2D individuals, our results showed that asymptomatic people with long-duration T1D possessed significant atherosclerotic and coronary microcirculatory risks, compared to T2D. Plasma metabolites associated with CVD in T1D may be different from T2D, with potential cardioprotection via markers of oxidative phosphorylation. Disclosure M. Yu: None. S. Jangolla: None. J. Gauthier: None. I. Wu: None. K. Park: None. Q. Li: None. C. Tsao: Stock/Shareholder; Current; AstraZeneca, Novartis Pharmaceuticals Corporation. H. Shah: None. G.L. King: None. Funding National Institutes of Health R01 HL161864-01; UO1 DK142331; and P30DK036836 (as part of the Joslin Diabetes Research Center Grant) Dianne Nunnally Hoppes Fund Thomas J. Beatson Foundation
YU et al. (Fri,) studied this question.