Paniagua J A, López-Miranda J, Pérez-Martínez P, Marín C, Vida J M, Fuentes F, Fernández de la Puebla R A, Pérez-Jiménez F
Lipid and Atherosclerosis Unit, University Hospital Reina Sofia, Córdoba, Spain.
Diabet Med. 2005 Dec;22(12):1647-56. doi: 10.1111/j.1464-5491.2005.01703.x.
To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers.
In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp (approximately 5.5 mmol/l; EHC) and a hyperglycemic clamp (approximately 20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured.
During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P<0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P<0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r=0.78, P=0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P<0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P<0.01 and P<0.05, respectively).
In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.
探讨HMG-CoA还原酶抑制剂（他汀类药物）治疗在血清葡萄糖变化期间对早期2型糖尿病（T2D）肥胖患者血浆氧化型低密度脂蛋白（ox-LDL）水平的作用及其与内皮生物标志物的关系。
在一项双盲、随机交叉研究中，15名接受饮食治疗的肥胖T2D患者接受西立伐他汀（0.4毫克/天）或安慰剂治疗3个月。在空腹时以及在正常血糖-高胰岛素钳夹试验（约5.5毫摩尔/升；EHC）和高血糖钳夹试验（约20毫摩尔/升；HC）期间测量循环ox-LDL水平。进行内皮依赖性血流介导的血管舒张（FMD）研究，并在静息时和EHC期间测量尿白蛋白排泄量（UAE）。还测量了可溶性细胞间黏附分子（s-ICAM）、可溶性血管细胞黏附分子（s-VCAM）和基础促血栓形成因子。
与安慰剂相比，西立伐他汀治疗期间，基础循环ox-LDL水平降低了48%（P<0.001）。与空腹状态相比，EHC期间血清ox-LDL水平降低，HC期间保持不变；在西立伐他汀治疗下，无论是空腹状态还是钳夹试验期间，这些水平均低于安慰剂。西立伐他汀治疗组的FMD高于安慰剂组（P<0.001），FMD的增加与血清ox-LDL水平的降低相关（r=0.78，P=0.001）。EHC期间微量白蛋白尿增加，但与安慰剂相比，西立伐他汀治疗期间这种增加有所减轻（P<0.05）。基础sICAM-1和sVCAM-1水平降低（分别为P<0.01和P<0.05）。
在早期肥胖2型糖尿病患者中，血清ox-LDL水平受短期血清葡萄糖变化影响，西立伐他汀治疗可使其降低。在西立伐他汀治疗期间，血流介导的内皮依赖性血管舒张改善与循环ox-LDL水平降低相关，高胰岛素血症诱导的尿白蛋白排泄减少。
