Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
J Diabetes Investig. 2024 Jul;15(7):805-816. doi: 10.1111/jdi.14172. Epub 2024 Feb 28.
Low levels of high-density lipoprotein-cholesterol (HDL-C) is considered a major cardiovascular risk factor. However, recent studies have suggested a more U-shaped association between HDL-C and cardiovascular disease. It has been shown that the cardioprotective effect of HDL is related to the functions of HDL particles rather than their cholesterol content. HDL particles are highly heterogeneous and have multiple functions relevant to cardiometabolic conditions including cholesterol efflux capacity, anti-oxidative, anti-inflammatory, and vasoactive properties. There are quantitative and qualitative changes in HDL as well as functional abnormalities in both type 1 and type 2 diabetes. Non-enzymatic glycation, carbamylation, oxidative stress, and systemic inflammation can modify the HDL composition and therefore the functions, especially in situations of poor glycemic control. Studies of HDL proteomics and lipidomics have provided further insights into the structure-function relationship of HDL in diabetes. Interestingly, HDL also has a pleiotropic anti-diabetic effect, improving glycemic control through improvement in insulin sensitivity and β-cell function. Given the important role of HDL in cardiometabolic health, HDL-based therapeutics are being developed to enhance HDL functions rather than to increase HDL-C levels. Among these, recombinant HDL and small synthetic apolipoprotein A-I mimetic peptides may hold promise for preventing and treating diabetes and cardiovascular disease.
低水平的高密度脂蛋白胆固醇（HDL-C）被认为是主要的心血管危险因素。然而，最近的研究表明，HDL-C 与心血管疾病之间存在更为 U 型的关联。已经表明，HDL 的心脏保护作用与 HDL 颗粒的功能有关，而不是与胆固醇含量有关。HDL 颗粒高度异质，具有与心脏代谢状况相关的多种功能，包括胆固醇流出能力、抗氧化、抗炎和血管活性特性。1 型和 2 型糖尿病患者的 HDL 存在定量和定性变化以及功能异常。非酶糖基化、氨甲酰化、氧化应激和全身炎症会改变 HDL 的组成，从而改变其功能，尤其是在血糖控制不佳的情况下。HDL 蛋白质组学和脂质组学的研究进一步深入了解了糖尿病中 HDL 的结构-功能关系。有趣的是，HDL 还具有多效性的抗糖尿病作用，通过改善胰岛素敏感性和β细胞功能来改善血糖控制。鉴于 HDL 在心脏代谢健康中的重要作用，正在开发基于 HDL 的治疗方法来增强 HDL 的功能，而不是增加 HDL-C 水平。其中，重组 HDL 和小合成载脂蛋白 A-I 模拟肽可能有希望预防和治疗糖尿病和心血管疾病。
