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.

中文翻译：

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糖尿病中的高密度脂蛋白：结构和功能相关性

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 与心血管疾病之间呈 U 形关联。研究表明，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 颗粒具有高度异质性，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 型糖尿病均存在 HDL 的量变和质变以及功能异常。非酶糖化、氨甲酰化、氧化应激和全身炎症可以改变 HDL 的组成，从而改变其功能，特别是在血糖控制不佳的情况下。HDL 蛋白质组学和脂质组学研究为糖尿病中 HDL 的结构-功能关系提供了进一步的见解。有趣的是，HDL 还具有多效抗糖尿病作用，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，基于 HDL 的治疗方法正在开发中，以增强 HDL 功能，而不是增加 HDL-C 水平。其中，重组 HDL 和小分子合成载脂蛋白 A-I 模拟肽可能有望用于预防和治疗糖尿病和心血管疾病。