Oki J C
Department of Medicine, University of Missouri-Kansas City 64108, USA.
Pharmacotherapy. 1995 May-Jun;15(3):317-37.
To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reduced inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs.
为了描述糖尿病患者的脂质和脂蛋白异常情况，并评估市售药物治疗的风险和益处，我们对美国国立医学图书馆数据库进行了MEDLINE检索，搜索1966年1月至1994年3月发表的研究。提取了评估对脂质和脂蛋白影响以及市售降脂药物不良反应的临床试验。如果综述和其他相关文章提供了有关脂质和脂蛋白代谢的信息或糖尿病患者血脂异常治疗指南，则将其纳入。未包括对氯贝丁酯的广泛综述。胰岛素依赖型糖尿病（IDDM）控制不佳的患者中最常见的血脂异常是甘油三酯和胆固醇水平同时升高，高密度脂蛋白（HDL）胆固醇降低（混合性高脂血症）。高甘油三酯血症合并HDL胆固醇降低是非胰岛素依赖型糖尿病患者中最常见的血脂异常，但基本上任何血脂异常模式都可能出现。糖尿病患者可能存在小而密的低密度脂蛋白（LDL）、脂蛋白糖基化以及氧化脂蛋白增加；所有这些都有助于加速动脉粥样硬化性心血管疾病。胰岛素治疗通常可纠正IDDM患者的定量脂质异常，因此很少需要药物治疗。饮食、运动以及胰岛素或口服磺脲类药物可改善高甘油三酯血症和低HDL浓度，但不一定能使其恢复正常。当非药物措施不足时，需进行药物治疗。根据每种药物对脂质和脂蛋白的影响、患者年龄、不良反应情况、患者耐受性以及药物与疾病和药物与药物之间的相互作用来给药。纤维酸衍生物是糖尿病患者明显高甘油三酯血症的首选药物。烟酸会使血糖控制恶化，但在严重高甘油三酯血症、高胆固醇血症或混合性高脂血症中可能需要使用。胆汁酸结合树脂可能会加重高甘油三酯血症，但对某些高胆固醇血症明显且甘油三酯正常的患者可能有用。对于LDL胆固醇升高和轻度高甘油三酯血症的患者，羟甲基戊二酰辅酶A还原酶抑制剂是首选。脂质异常明显或混合性高脂血症患者可能需要谨慎联合使用降脂药物。
