Unidad de Investigación de Enfermedades Metabólicas Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico; Institute for Obesity Research, Tecnologico de Monterrey, México City, Mexico; Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, México City, Mexico.
Unidad de Investigación de Enfermedades Metabólicas Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico.
Atherosclerosis. 2024 Jul;394:117213. doi: 10.1016/j.atherosclerosis.2023.117213. Epub 2023 Aug 3.
Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of mortality among patients with Type 2 Diabetes Mellitus (T2DM). In this population, High-Density Lipoprotein (HDL) particles exhibit abnormalities in number, composition, and function, culminating in diminished anti-atherosclerotic capabilities despite normal HDL cholesterol (HDL-C) concentrations. Hyperglycemic conditions contribute to these alterations in HDL kinetics, composition, and function, causing T2DM patients' HDL particles to exhibit decreased concentrations of diverse lipid species and proteins. Treatment of hyperglycemia has the potential to correct abnormal HDL particle attributes in T2DM; however, pharmacological interventions, including metformin and thiazolidinediones, yield inconsistent outcomes with respect to HDL-C concentrations and functionality. Despite numerous attempts with diverse drugs, pharmacologically augmenting HDL-C levels has not resulted in clinical benefits in mitigating ASCVD risk. In contrast, reducing Low Density Lipoprotein cholesterol (LDL-C) via statins and ezetimibe has demonstrated significant efficacy in curtailing CVD risk among T2DM individuals. Promising results have been observed in animal models and early-phase trials utilizing recombinant HDL and Lecitin Cholesterol Acyl Transferase (LCAT) -enhancing agents, but the evaluation of their efficacy and safety in large-scale clinical trials is ongoing. While aberrant HDL metabolism constitutes a prevalent aspect of dyslipidemia in T2DM, HDL cholesterol concentrations and composition no longer offer valuable insights for informing therapeutic decisions. Nevertheless, HDL metabolism remains a critical research area in T2DM, necessitating further investigation to elucidate the role of HDL particles in the development of diabetes-associated complications.
动脉粥样硬化性心血管疾病（ASCVD）是 2 型糖尿病（T2DM）患者死亡的主要原因。在该人群中，高密度脂蛋白（HDL）颗粒的数量、组成和功能存在异常，尽管 HDL 胆固醇（HDL-C）浓度正常，但抗动脉粥样硬化能力降低。高血糖状态导致 HDL 动力学、组成和功能发生这些改变，导致 T2DM 患者的 HDL 颗粒中各种脂质和蛋白质的浓度降低。治疗高血糖有可能纠正 T2DM 中 HDL 颗粒的异常属性；然而，包括二甲双胍和噻唑烷二酮在内的药物干预在 HDL-C 浓度和功能方面的结果不一致。尽管使用了多种药物进行了多次尝试，但通过药理学方法增加 HDL-C 水平并未在减轻 ASCVD 风险方面带来临床获益。相比之下，通过他汀类药物和依折麦布降低低密度脂蛋白胆固醇（LDL-C）已证明在减少 T2DM 个体的 CVD 风险方面具有显著疗效。在使用重组 HDL 和 Lecitin 胆固醇酰基转移酶（LCAT）增强剂的动物模型和早期临床试验中观察到了有希望的结果，但它们在大规模临床试验中的疗效和安全性评估仍在进行中。虽然异常的 HDL 代谢是 T2DM 中血脂异常的一个普遍特征，但 HDL 胆固醇浓度和组成不再为治疗决策提供有价值的信息。然而，HDL 代谢仍然是 T2DM 中的一个关键研究领域，需要进一步研究阐明 HDL 颗粒在糖尿病相关并发症发展中的作用。
