Srivastava Anand, Adams-Huet Beverley, Vega Gloria L, Toto Robert D
Division of Renal Medicine, Brigham &Women's Hospital, Boston, Massachusetts, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Investig Med. 2016 Aug;64(6):1102-8. doi: 10.1136/jim-2016-000102. Epub 2016 Jul 7.
Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo -24.6%, los -38.2%, spiro -51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (-20.9% vs +34.3%, p<0.01), V+I C(-18.8% vs +21.3%, p<0.01), and V+I-ApoB (-13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins.
NCT00381134; Results.
血管紧张素转换酶抑制剂（ACEi）和血管紧张素受体阻滞剂（ARBs）可改善糖尿病和蛋白尿患者的血脂异常。联合使用ACEi+ARB或ACEi+盐皮质激素受体阻滞剂是否能改善血脂异常尚不清楚。我们假设，对于糖尿病肾病（DN）患者，每日一次加用100 mg氯沙坦或25 mg螺内酯并联合每日一次80 mg赖诺普利进行长期给药可改善血脂异常。在一项针对81例DN患者的48周随机、双盲、安慰剂对照试验中，我们每隔12周测量血脂水平、极低密度（V）、中间密度（I）、低密度（LDL）、高密度（HDL）脂蛋白、LDL颗粒大小及其各自的胆固醇（C）和载脂蛋白B水平（ApoB），以及尿白蛋白/肌酐比值（UACR）。采用酶法分析血浆脂质和脂蛋白C，化学法测定Apo B。通过混合模型重复测量分析数据。各治疗组间的ΔUACR存在差异（安慰剂组为-24.6%，氯沙坦组为-38.2%，螺内酯组为-51.6%，p=0.02）。ΔUACR与ΔTG或任何脂质或脂蛋白测量值之间均无相关性。与安慰剂氯沙坦相比，而非螺内酯，可降低TG（-20.9%对+34.3%，p<0.01）、V+I C（-18.8%对+21.3%，p<0.01）以及V+I-ApoB（-13.2%对+21%，p<0.01）。体重、糖化血红蛋白或其他脂蛋白变量无显著变化。我们得出结论，氯沙坦可改善DN患者的血脂异常。我们推测其机制是改善了极低密度脂蛋白和残余脂蛋白的清除。
NCT00381134；结果。
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