Pathophysiology of Diabetic Dyslipidemia.
Pathophysiology of Diabetic Dyslipidemia.
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DOI：
10.5551/jat.rv17023
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发表时间：
2018-09-01
影响因子：
4.4
通讯作者：
Hirano T
中科院分区：
文献类型：
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作者：
Hirano T
越来越多的临床证据表明，血清甘油三酯 (TG) 是动脉粥样硬化性心血管疾病的主要预测因子，与 2 型糖尿病人群中的低密度脂蛋白 (LDL)-胆固醇 (C) 相当，超过了血红蛋白 A1c 的预测能力。糖尿病中的动脉粥样硬化性血脂异常包括富含 TG 的脂蛋白 (TRL) 血清浓度升高、小而密的低密度脂蛋白 (LDL) 的高患病率以及富含胆固醇的高密度脂蛋白 (HDL)2-C 的低浓度。中枢脂蛋白异常是指大量富含 TG 的极低密度脂蛋白 (VLDL)1 增加，其他脂蛋白异常在代谢上与 TRL 增加有关。胰岛素通过抑制肝脏 VLDL 产生并通过激活脂蛋白脂肪酶刺激 VLDL 去除来严格调节血清 VLDL 浓度。胰岛素抵抗代偿性高胰岛素血症是否与 VLDL 过量产生因果关系仍存在争议。本综述介绍了实验和临床观察结果，表明胰岛素抵抗而非高胰岛素血症会刺激肝脏 VLDL 的产生。 LDL 和 HDL 由不同尺寸和密度的异质颗粒组成。胆固醇耗尽的小密度低密度脂蛋白和富含胆固醇的高密度脂蛋白2亚种特别容易受到胰岛素抵抗的影响，可以分别命名为“代谢性低密度脂蛋白和高密度脂蛋白”。我们分别建立了定量小密 LDL-C 和小密 HDL(HDL3)-C 的直接测定法。从 HDL-C 中减去 HDL3-C 得到 HDL2-C。我将解释通过我们的测定确定的 LDL 和 HDL 亚种测量值的临床相关性。糖尿病肾病（DKD）会显着恶化血浆脂质状况，从而增加动脉粥样硬化的风险。最后，我简要概述了与 DKD 相关的血脂异常的病理生理学，其他评论文章并未对此进行太多讨论。
Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power of hemoglobinA1c. Atherogenic dyslipidemia in diabetes consists of elevated serum concentrations of TG-rich lipoproteins (TRLs), a high prevalence of small dense low-density lipoprotein (LDL), and low concentrations of cholesterol-rich high-density lipoprotein (HDL)2-C. A central lipoprotein abnormality is an increase in large TG-rich very-low-density lipoprotein (VLDL)1, and other lipoprotein abnormalities are metabolically linked to increased TRLs. Insulin critically regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal by activation of lipoprotein lipase. It is still debated whether hyperinsulinemia compensatory for insulin resistance is causally associated with the overproduction of VLDL. This review introduces experimental and clinical observations revealing that insulin resistance, but not hyperinsulinemia stimulates hepatic VLDL production. LDL and HDL consist of heterogeneous particles with different size and density. Cholesterol-depleted small dense LDL and cholesterol-rich HDL2 subspecies are particularly affected by insulin resistance and can be named “Metabolic LDL and HDL,” respectively. We established the direct assays for quantifying small dense LDL-C and small dense HDL(HDL3)-C, respectively. Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain clinical relevance of measurements of LDL and HDL subspecies determined by our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, I briefly overview pathophysiology of dyslipidemia associated with DKD, which has not been so much taken up by other review articles.