Abstract
AIMS/HYPOTHESIS: CVD remains a major cause of mortality in people with long-duration type 1 diabetes, even among those without diabetic kidney disease (DKD). We assessed biomarkers that may be associated with CVD risks among the Joslin 'Medalists', namely those with type 1 diabetes of ≥50 years. METHODS: In this cross-sectional study, participants were evaluated for self-reported CVD (n=1038), with subsets undergoing coronary artery calcium (CAC; n=142) and cardiac magnetic resonance (CMR; n=111) imaging. Using multivariable regression analysis, multiple circulating factors such as inflammatory biomarkers and osteopontin (n=300) were analysed for associations with CVD, CAC and CMR, adjusting for DKD and other cardiometabolic and glycaemic risk factors, including HbA(1c), continuous glucose monitor (n=102) metrics and advanced glycation end-products (n=200). RESULTS: Only 32% of participants had DKD (eGFR <60 ml/min per 1.73 m(2)), but 40% had CVD. Despite having excellent cardiometabolic management (mean blood pressure of 132/64 mmHg; LDL and HDL-cholesterol of 2.10 mmol/l and 1.69 mmol/l, respectively, and a median HbA(1c) of 54.1 mmol/mol [7.1%]), participants exhibited a high CAC burden (median score 937), which did not differ between those with and without DKD (1136 vs 878, respectively). Among the glycaemic markers, HbA(1c), but not hypoglycaemia or glycaemic variability, remained associated with CVD (OR 1.40, p<0.01) in the non-DKD group compared with the DKD group. Similarly, among the inflammatory markers, only osteopontin was associated with CVD (β=0.50, p<0.01) in the non-DKD group compared with the DKD group. CONCLUSIONS/INTERPRETATION: Ageing people with long-duration type 1 diabetes and without DKD, but with excellent cardiometabolic management, still possess a high burden of coronary atherosclerosis. Improving hyperglycaemia and mitigating inflammation, especially osteopontin, are potentially important for the management of CVD in long-duration type 1 diabetes.