OBJECTIVE A subset of people with long-standing type 1 diabetes (T1D) appears to be protected from microvascular and macrovascular complications. Previous studies have focused on improved abilities to respond to glucose and its downstream effects as protective mechanisms. It is unclear whether lipoproteins play a role in the vascular health of these people. We therefore determined whether HDL particle concentration, size, function, and/or protein composition associate with protection from vascular complications. RESEARCH DESIGN AND METHODS We studied two independent cross-sectional cohorts with T1D: the T1D Exchange Living Biobank (n = 47) and the Joslin Medalist Study (n = 100). Some of the subjects had vascular complications, whereas others never exhibited vascular complications, despite an average duration of diabetes in the cohorts of 45 years. We assessed HDL particle size and concentration by calibrated ion mobility analysis, the HDL proteome by targeted mass spectrometry, and HDL function ex vivo by quantifying cholesterol efflux capacity and inhibition of monocyte adhesion to endothelial cells. RESULTS In both cohorts, people without vascular complications exhibited significantly higher concentrations of medium-sized HDL particles (M-HDL) independently of total and HDL cholesterol levels. While no consistent differences in HDL functions were observed ex vivo, people without vascular complications had higher levels of HDL-associated paraoxonase 1 (PON1), an enzyme that inhibits atherosclerosis in animal models. CONCLUSIONS Elevated concentrations of M-HDL particles and elevated levels of HDL-associated PON1 may contribute to long-term protection from the vascular complications of diabetes by pathways that are independent of total cholesterol and HDL cholesterol.

中文翻译：

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高浓度的中型HDL颗粒和HDL对氧磷酶1的丰富与长期患有1型糖尿病的人的血管并发症的预防相关。

目的患有长期1型糖尿病（T1D）的人的一部分似乎受到保护，免受微血管和大血管并发症的影响。先前的研究集中于提高对葡萄糖的反应能力及其作为保护机制的下游作用。尚不清楚脂蛋白是否在这些人的血管健康中起作用。因此，我们确定HDL颗粒浓度，大小，功能和/或蛋白质组成是否与保护血管并发症无关。研究设计和方法我们研究了T1D的两个独立的横断面队列：T1D交换生活生物库（n = 47）和Joslin Medalist研究（n = 100）。一些受试者患有血管并发症，而其他受试者从未表现出血管并发症，尽管该人群的平均糖尿病持续时间为45年。我们通过校准的离子迁移率分析评估了HDL的粒径和浓度，通过靶向质谱分析了H​​DL蛋白质组，并通过定量胆固醇外排量和抑制单核细胞粘附于内皮细胞来评估了HDL的离体功能。结果在这两个队列中，无血管并发症的人均表现出明显较高的中型HDL颗粒（M-HDL）浓度，而与总胆固醇和HDL胆固醇水平无关。尽管离体观察到HDL功能没有一致的差异，但没有血管并发症的人的HDL相关对氧磷酶1（PON1）含量较高，该酶在动物模型中可抑制动脉粥样硬化。