Cochran Blake J, King Thomas W, Chemello Kevin, Thomas Shane R, Rye Kerry-Anne
Cardiometabolic Research Group, School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
Nat Rev Endocrinol. 2025 Sep 17. doi: 10.1038/s41574-025-01176-y.
Epidemiological studies have identified an inverse association of high-density lipoprotein (HDL) cholesterol with cardiovascular risk. Preclinical studies have shown that HDLs also exhibit cardioprotective functions in cultured cells and animal models. However, large, randomized, placebo-controlled clinical trials of HDL-raising agents have failed to reduce cardiovascular events in humans. Despite this negative outcome, glycaemic control was considerably improved in the patients with type 2 diabetes mellitus who were recruited into these trials. This finding indicated that HDLs might have anti-diabetic functions. This was shown to be the case in cell studies and animal studies, which have established that HDLs and apolipoprotein A1, the main HDL apolipoprotein, improve pancreatic β-cell function and increase insulin sensitivity. On the other hand, diabetes mellitus adversely affects the structure, anti-diabetic functions and cardioprotective functions of HDLs. These complex, closely linked relationships, which are undoubtedly worthy of further investigation, form the focus of this Review.
流行病学研究已确定高密度脂蛋白（HDL）胆固醇与心血管风险呈负相关。临床前研究表明，HDL在培养细胞和动物模型中也具有心脏保护功能。然而，提高HDL药物的大型随机安慰剂对照临床试验未能降低人类心血管事件。尽管有这个负面结果，但纳入这些试验的2型糖尿病患者的血糖控制有了显著改善。这一发现表明HDL可能具有抗糖尿病功能。细胞研究和动物研究证实了这一点，这些研究表明HDL和主要的HDL载脂蛋白载脂蛋白A1可改善胰腺β细胞功能并提高胰岛素敏感性。另一方面，糖尿病会对HDL的结构、抗糖尿病功能和心脏保护功能产生不利影响。这些复杂且紧密相连的关系无疑值得进一步研究，构成了本综述的重点。
