Diabetic dyslipidemia
Diabetic dyslipidemia
复制标题
DOI：
10.1016/s0002-9149(98)00848-0
复制
发表时间：
1998-12-17
影响因子：
2.8
通讯作者：
Kreisberg, RA
中科院分区：
文献类型：
--
作者：
Kreisberg, RA
冠心病的血管危险因素仅占糖尿病动脉粥样硬化风险增加的25-50%。其他明显的危险因素是高血糖和血脂异常。然而，高血糖症是从胰岛素抵抗到明显糖尿病的一系列事件中的一个非常晚期的阶段，而脂蛋白异常在很大程度上无症状的糖尿病前驱症状期间表现出来，并大大增加了大血管疾病的风险。胰岛素抵抗性糖尿病过程几乎影响所有脂质和脂蛋白。乳糜微粒和极低密度脂蛋白（VLDL）残留物积聚，甘油三酯富集高密度脂蛋白（HDL）和低密度脂蛋白（LDL），导致高水平的潜在致动脉粥样硬化颗粒和低水平的HDL胆固醇。高脂血症最终会损害富含甘油三酯的脂蛋白的清除，其积累会加重高甘油三酯血症。随着甘油三酯的增加-仍然在所谓的正常范围内-HDL和LDL的异常变得更加明显。因此，当甘油三酯高于200 mg/dL时，LDL颗粒小而致密（当它们低于90 mg/dL时，颗粒大而有浮力）。小而致密的LDL颗粒的致动脉粥样硬化性归因于它们对氧化的敏感性增加，但在许多患者中，它们可能是胰岛素抵抗或致动脉粥样硬化VLDL存在的标志物。高甘油三酯血症与动脉粥样硬化相关，因为（1）它是胰岛素抵抗和致动脉粥样硬化代谢异常的标志物;和（2）富含甘油三酯的脂蛋白的小尺寸使它们能够渗透血管壁，在血管壁中它们被氧化，结合巨噬细胞上的受体，并被摄入，导致动脉粥样硬化病变的发展。各种研究（吉非罗齐一级预防：赫尔辛基心脏研究;辛伐他汀和普伐他汀二级预防：斯堪的纳维亚辛伐他汀生存研究[4S]和胆固醇和复发事件[CARE]，他汀类药物的风险降低率为22%-50%，贝特类药物的风险降低率为65%。相对于安慰剂。还注意到（在4S和CARE中）未经治疗的糖尿病患者发生主要冠状动脉事件的风险是未经治疗的非糖尿病患者的1.5-1.7倍。虽然吉非罗齐（纤维酸衍生物）在降低糖尿病患者的甘油三酯和增加HDL胆固醇方面比他汀类药物更有效，但它不会改变，甚至可能增加LDL-胆固醇水平（非诺贝特可能是一个例外，在一些研究中降低LDL胆固醇20-25%）。然而，吉非罗齐确实增加LDL颗粒尺寸。尽管如此，他汀类药物是目前首选的降脂药物，因为LDL-胆固醇与HDL-胆固醇比值的变化优于吉非罗齐。此外，糖尿病患者可能比非糖尿病患者更有可能从他汀类药物治疗中获益。需要注意的是，理论上，烟酸可以纠正或改善2型糖尿病患者的所有脂质或脂蛋白异常。不幸的是，它是相对禁忌的，因为它会引起胰岛素抵抗，并可能导致或加重高血糖症（除了其他众所周知的副作用，如潮红，胃刺激，肝毒性的发展和高尿酸血症）。目前尚不清楚较新的制剂，如每日一次Niaspan是否可以更好地耐受糖尿病。在任何情况下，大多数2型糖尿病患者都有冠状动脉疾病的危险因素，并有资格接受积极的LDL降胆固醇治疗。同时，目前尚不清楚改善血糖控制是否会降低此类患者的冠状动脉疾病风险。(C)1998年，Excerpta Medica，Inc.
Usual risk factors for coronary artery disease account for only 25-50% of increased atherosclerotic risk in diabetes mellitus. Other obvious risk factors are hyperglycemia and dyslipidemia. However, hyperglycemia is a very late stage in the sequence of events from insulin resistance to frank diabetes, whereas lipoprotein abnormalities are manifested during the largely asymptomatic diabetic prodrome and contribute substantially to the increased risk of macrovascular disease. The insulin-resistant diabetes course affects virtually all lipids and lipoproteins. Chylamicron and very-low-density lipoprotein (VLDL) remnants accumulate, and triglycerides enrich high-density lipoprotein (HDL) and low-density lipoprotein (LDL), leading to high levels of potentially atherogenic particles and low levels of HDL cholesterol. Hyperglycemia eventually impairs removal of triglyceride-rich lipoproteins, the accumulation of which accentuates hypertriglyceridemia. As triglycerides increase - still within the so-called normal range - abnormalities in HDL and LDL became more apparent. Thus, when triglycerides are greater-than 200 mg/dL, LDL particles are small and dense (when they are less-than 90 mg/dL, the particles are of the large, buoyant variety). The atherogenicity of small, dense LDL particles is attributed to their increased susceptibility to oxidation, but in many patients they may be a marker for insulin resistance or the presence of atherogenic VLDL. Hypertriglyceridemia is associated with atherosclerosis because (1) it is a marker for insulin resistance and atherogenic metabolic abnormalities; and (2) the small size of triglyceride-enriched lipoproteins enables them to infiltrate the blood vessel wall where they are oxidized, bind to receptors on macrophages, and ingested, leading to the development of the atherosclerotic lesion. Various studies (primary prevention with gemfibrozil: Helsinki Heart Study; secondary prevention with simvastatin and pravastatin: Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events [CARE], respectively) have demonstrated that lipid-lowering therapy in type 2 diabetes is effective in decreasing the number of cardiac events.Risk reduction was 22% to 50% (statins) and similar to 65% (fibrate) relative to placebo. It was also noted (in 4S and CARE) that the risk of major coronary events in untreated diabetic patients was 1.5-1.7-fold greater than in untreated nondiabetic patients. Although gemfibrozil (fibric acid derivative) is more effective in decreasing triglycerides and increasing HDL cholesterol in diabetic patients than the statins, it does not change and may even increase LDL-cholesterol levels (fenofibrate may be an exception, decreasing LDL cholesterol by 20-25% in some studies). However, gemfibrozil does increase LDL particle size. Nevertheless, the statins are the current lipid-lowering drugs of choice because the change in LDL-cholesterol-to-HDL-cholesterol ratio is better than with gemfibrozil. Moreover, the diabetic patient may be more likely to benefit from statin therapy than the nondiabetic patient. It should be noted that, in theory, nicotinic acid can correct or improve all lipid or lipoprotein abnormalities in patients with type 2 diabetes. Unfortunately, it is relatively contraindicated because it causes insulin resistance and may precipitate or aggravate hyperglycemia (in addition to its other well-known side effects such as flushing, gastric irritation, development of hepatotoxicity, and hyperuricemia). It is unknown at present whether newer formulations such as once-daily Niaspan may be better tolerated in diabetes. In any case, most patients with type 2 diabetes have risk factors for coronary artery disease and qualify for aggressive LDL cholesterol-lowering therapy. At the same time, it is presently unknown whether improved glycemic control decreases coronary artery disease risk in such patients. (C) 1998 by Excerpta Medica, Inc.