180-OR: Glycemic Markers Are Differentially Associated with Cardiovascular Imaging and Outcomes in Long-Duration Type 1 Diabetes

Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). While glycemic control is related to CVD outcomes in T1D, there is a lack of information on the risk of glycemic excursions and comparative contributions of glycemic markers to CVD in aging populations with T1D. Among the Joslin “Medalists” with T1D≥50 years (n=1043), mean historical HbA1c was obtained across longitudinal visits (median 4.1 years), while a single consecutive 14-day block of continuous glucose monitoring (CGM) data was remotely obtained from a subset of Medalist CGM users (n=110). Additionally, Medalists underwent coronary artery calcification scans (CAC; n=153) and cardiac magnetic resonance imaging of left ventricular (LV) structure and function (CMR; n=111). In the overall cohort, HbA1c was associated with CVD (p<0.001). CGM metrics for hyperglycemia (mean glucose, p=0.03; glucose management indicator, p=0.03; and time above range>180 mg/dL, p=0.02), but not hypoglycemia or day-to-day glycemic variability, were associated with LV remodeling. Plasma assays for advanced glycation end-products (AGEs; n=200), N-carboxyethyl-lysine (CEL), N-carboxymethyl-lysine (CML), and methylglyoxal-derived hydroimidazolone (MGH1), showed associations with CVD (p=0.04, p=0.04, and p=0.01, respectively); CAC (p=0.05, p=0.01, and p=0.01, respectively); and LV remodeling (p=0.09, p=0.05, and p=0.04, respectively). The association of CEL with CVD replicated in a separate Medalist subset (n=311) with self-reported CVD data (p=0.01). These findings indicated that glycemic parameters assessing long-term, irreversible markers of hyperglycemia (AGEs) are the strongest drivers of CVD in people with long-duration T1D, as compared to hypoglycemia or day-to-day glycemic variability. Our results highlight the need for glycemic control in aging populations with T1D, even after other risk factors like hyperlipidemia and hypertension have been controlled.