Yu Marc Gregory, Shah Hetal, Jangolla Surya, Gauthier John, Viebranz Elizabeth, Wu I-Hsien, Chokshi Tanvi, Park Kyoungmin, Li Qian, Fickweiler Ward, Jha Mawra, Sun Jennifer, Blankstein Ron, Tsao Connie, King George L
Dianne Nunnally Hoppes Laboratory, Research Division, Joslin Diabetes Center, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Diabetologia. 2025 Aug 20. doi: 10.1007/s00125-025-06521-4.
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.
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, continuous glucose monitor (n=102) metrics and advanced glycation end-products (n=200).
Only 32% of participants had DKD (eGFR <60 ml/min per 1.73 m), 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 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, 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.
目的/假设：心血管疾病（CVD）仍然是长期1型糖尿病患者死亡的主要原因，即使在那些没有糖尿病肾病（DKD）的患者中也是如此。我们评估了乔斯林“奖章获得者”（即患有≥50年1型糖尿病的患者）中可能与CVD风险相关的生物标志物。
在这项横断面研究中，对自我报告患有CVD的参与者（n = 1038）进行了评估，其中部分参与者接受了冠状动脉钙化（CAC；n = 142）和心脏磁共振成像（CMR；n = 111）检查。使用多变量回归分析，分析了多种循环因子，如炎症生物标志物和骨桥蛋白（n = 300）与CVD、CAC和CMR的关联，并对DKD以及其他心脏代谢和血糖风险因素进行了校正，这些因素包括糖化血红蛋白（HbA）、连续血糖监测指标（n = 102）和晚期糖基化终产物（n = 200）。
只有32%的参与者患有DKD（估算肾小球滤过率<60 ml/min/1.73m²），但40%的参与者患有CVD。尽管这些参与者的心脏代谢管理良好（平均血压为132/64 mmHg；低密度脂蛋白和高密度脂蛋白胆固醇分别为2.10 mmol/l和1.69 mmol/l，糖化血红蛋白中位数为54.1 mmol/mol [7.1%]），但其冠状动脉钙化负担仍然很高（中位数为937），在有DKD和无DKD的参与者之间并无差异（分别为1136和878）。在血糖标志物中，与DKD组相比，非DKD组中糖化血红蛋白而非低血糖或血糖变异性仍然与CVD相关（比值比1.40，p<0.01）。同样，在炎症标志物中，与DKD组相比，非DKD组中只有骨桥蛋白与CVD相关（β = 0.50，p<0.01）。
结论/解读：患有长期1型糖尿病且无DKD但心脏代谢管理良好的老年人，仍然具有较高的冠状动脉粥样硬化负担。改善高血糖和减轻炎症，尤其是减轻骨桥蛋白水平，对于长期1型糖尿病患者的CVD管理可能具有重要意义。
