Koshel'skaia O A, Vinnitskaia I V, Konko T Iu, Kravchenko E S, Suslova T E, Karpov R S
Kardiologiia. 2015;55(3):67-74.
This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT).
A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n = 16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n = 15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l)/22.5) was calculated.
During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group 1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p < 0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% 16.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p < 0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r = 0.37, p = 0.04) in the entire group of patients (n = 31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r = -0.57, p = 0.034).
In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.
本开放性随机研究比较了瑞舒伐他汀以及阿托伐他汀与依折麦布联合使用24周的治疗方案，对冠心病合并2型糖尿病或糖耐量受损（IGT）患者碳水化合物代谢参数及血浆脂肪因子水平的影响。
本研究共纳入31例冠心病合并2型糖尿病或IGT患者。患者被随机分为两组：第1组患者接受平均剂量为12.5mg/天的瑞舒伐他汀治疗（n = 16）；第2组患者接受平均剂量为13.3mg/天的阿托伐他汀与依折麦布（10mg）联合治疗（n = 15）。评估血脂、载脂蛋白B、载脂蛋白A1、血糖、胰岛素、瘦素和脂联素的血浆水平；计算HOMA-IR指数（空腹胰岛素，μ/l×空腹血糖，mmol/l）/22.5）。
治疗期间，第1组的低密度脂蛋白胆固醇（LDL-C）和载脂蛋白B水平分别下降了51.7%和42.3%，第2组分别下降了51.8%和44.9%。第2组甘油三酯水平的降低明显比第1组更显著：分别为43.2%和17.4%（p < 0.02），而两组中高密度脂蛋白胆固醇（HDL-C）和载脂蛋白A1均未观察到显著变化。仅在第2组中发现基础血糖、基础胰岛素血症、糖化血红蛋白（HbA1c）水平升高（从6.47%[6.10 - 7.02%]升至6.98%[6.23 - 8.18%]）以及HOMA-IR升高（从2.14[1.68 - 3.51]升至4.30[2.31 - 5.77]）（所有p < 0.05）。在第2组75%的患者中观察到这些变化，与糖尿病状态或IGT的存在无关，但在碳水化合物代谢紊乱的患者中变化更明显。治疗期间瘦素水平变化多样：第1组73%的患者瘦素水平下降，而第2组67%的患者瘦素浓度升高57%。在整个患者组（n = 31）中，基础血糖升高程度与瘦素水平升高相关（r = 0.37，p = 0.04）。此外，瘦素水平变化与脂联素水平降低呈负相关（r = -0.57，p = 0.034）。
在LDL-C水平降低程度相当的情况下，与瑞舒伐他汀治疗不同，阿托伐他汀与依折麦布联合24周治疗会导致基础血糖、胰岛素血症、HbA1c和HOMA-IR指数升高，无论治疗前是否存在碳水化合物代谢紊乱。我们的数据表明，脂联素和瘦素参与了阿托伐他汀与依折麦布联合使用产生不良代谢影响的机制。
