Subramanian Savitha, Chait Alan
Diabetes Obesity Center of Excellence, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, USA.
Biochim Biophys Acta. 2012 May;1821(5):819-25. doi: 10.1016/j.bbalip.2011.10.003. Epub 2011 Oct 8.
Hypertriglyceridemia is a common lipid abnormality in persons with visceral obesity, metabolic syndrome and type 2 diabetes. Hypertriglyceridemia typically occurs in conjunction with low HDL levels and atherogenic small dense LDL particles and is associated with increased cardiovascular risk. Insulin resistance is often an underlying feature and results in increased free fatty acid (FFA) delivery to the liver due to increased peripheral lipolysis. Increased hepatic VLDL production occurs due to increased substrate availability via FFAs, decreased apolipoprotein B100 degradation and increased lipogenesis. Postprandial hypertriglyceridemia also is a common feature of insulin resistance. Small dense LDL that coexist with decreased HDL particles in hypertriglyceridemic states are highly pro-atherogenic due to their enhanced endothelial permeability, proteoglycan binding abilities and susceptibility to oxidation. Hypertriglyceridemia also occurs in undertreated individuals with type 1 diabetes but intensive glucose control normalizes lipid abnormalities. However, development of visceral obesity in these patients unravels a similar metabolic profile as in patients with insulin resistance. Modest hypertriglyceridemia increases cardiovascular risk, while marked hypertriglyceridemia should be considered a risk for pancreatitis. Lifestyle modification is an important therapeutic strategy. Drug therapy is primarily focused on lowering LDL levels with statins, since efforts at triglyceride lowering and HDL raising with fibrates and/or niacin have not yet been shown to be beneficial in improving cardiovascular risk. Fibrates, however, are first-line agents when marked hypertriglyceridemia is present. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.
高甘油三酯血症是内脏肥胖、代谢综合征和2型糖尿病患者常见的脂质异常。高甘油三酯血症通常与低高密度脂蛋白水平和致动脉粥样硬化的小而密低密度脂蛋白颗粒同时出现，并与心血管风险增加相关。胰岛素抵抗往往是一个潜在特征，由于外周脂肪分解增加，导致游离脂肪酸（FFA）输送到肝脏增加。由于通过FFA增加了底物可用性、载脂蛋白B100降解减少和脂肪生成增加，肝脏极低密度脂蛋白（VLDL）生成增加。餐后高甘油三酯血症也是胰岛素抵抗的一个常见特征。在高甘油三酯血症状态下与高密度脂蛋白颗粒减少共存的小而密低密度脂蛋白因其增强的内皮通透性、蛋白聚糖结合能力和氧化易感性而具有高度促动脉粥样硬化性。1型糖尿病治疗不足的患者也会出现高甘油三酯血症，但强化血糖控制可使脂质异常恢复正常。然而，这些患者内脏肥胖的发展揭示了与胰岛素抵抗患者相似的代谢特征。轻度高甘油三酯血症会增加心血管风险，而明显的高甘油三酯血症应被视为胰腺炎的一个风险因素。生活方式改变是一项重要的治疗策略。药物治疗主要集中于用他汀类药物降低低密度脂蛋白水平，因为用贝特类药物和/或烟酸降低甘油三酯水平和升高高密度脂蛋白水平的努力尚未被证明对改善心血管风险有益。然而，当存在明显高甘油三酯血症时，贝特类药物是一线药物。本文是名为“甘油三酯代谢与疾病”的特刊的一部分。
