Risk and protective factors for coronary atherosclerosis and myocardial dysfunction in individuals with long-duration type 1 diabetes.

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 m²), 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.