Kadoglou N P E, Kapelouzou A, Tsanikidis H, Vitta I, Liapis C D, Sailer N
First Department of Internal Medicine, Hippokratio General Hospital of Thessaloniki, Greece.
Exp Clin Endocrinol Diabetes. 2011 Feb;119(2):63-8. doi: 10.1055/s-0030-1265174. Epub 2010 Oct 28.
Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose-tissue derivatives, known as adipokines, which mediate insulin resistance. The aim of the present study was to evaluate the effects of metformin and rosiglitazone on serum levels of those novel adipokines in drug-naïve patients with type 2 diabetes mellitus (T2DM).
140 patients with T2DM, already treated with diet, but without adequate glycemic control (HbA1c > 7%), were randomly assigned to: RSG+MET group, (n = 70): Combination therapy with fixed dose of 4 mg rosiglitazone plus 500 mg metformin. MET group, (n = 70): Half-maximum dose of metformin monotherapy (1 700 mg/day). Before and after 6-month treatment, body-mass index (BMI), blood pressure (BP), fat-mass, fasting plasma glucose (FPG), HbA1c, insulin resistance indexes (HOMA-IR, insulin), lipids, high-sensitivity CRP (hsCRP), vaspin, adiponectin, and interleukin-6 (IL-6) were measured.
Glucose regulation and insulin resistance were equivalently improved from baseline within both groups (p < 0.05). There was a considerable amelioration of hsCRP, WBC, adiponectin, IL-6, systolic and diastolic BP with rosiglitazone/metformin combined treatment as compared to baseline (p < 0.05) and MET group (p < 0.05). In contrast, metformin monotherapy significantly reduced BMI (p < 0.001), total-cholesterol (p = 0.012) and LDL (p = 0.020) levels compared to RSG+MET group. Importantly, serum vaspin concentration was equivalently decreased from baseline in both RSG+MET (-0.96 ± 0.75 ng/ml, p < 0.001) and MET (-0.92 ± 0.57 ng/ml, p=0.001) group. The aforementioned vaspin changes correlated with changes in WHR, HbA1c, FPG, HOMA-IR, insulin, IL-6 (only in the RSG+MET group) and fat-mass. In standard multiple regression analysis, FPG, HbA1c, HOMA-IR and insulin remained independent determinants of serum vaspin levels changes (R² = 0.836, p = 0.004).
Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naïve patients with T2DM.
内脏脂肪素、脂联素和白细胞介素-6（IL-6）是新型脂肪组织衍生物，即脂肪因子，可介导胰岛素抵抗。本研究旨在评估二甲双胍和罗格列酮对初治2型糖尿病（T2DM）患者血清中这些新型脂肪因子水平的影响。
140例已接受饮食治疗但血糖控制不佳（糖化血红蛋白>7%）的T2DM患者被随机分为：RSG+MET组（n = 70）：固定剂量4 mg罗格列酮加500 mg二甲双胍联合治疗；MET组（n = 70）：二甲双胍单药治疗的半最大剂量（1700 mg/天）。在6个月治疗前后，测量体重指数（BMI）、血压（BP）、脂肪量、空腹血糖（FPG）、糖化血红蛋白、胰岛素抵抗指数（HOMA-IR、胰岛素）、血脂、高敏C反应蛋白（hsCRP）、内脏脂肪素、脂联素和白细胞介素-6（IL-6）。
两组患者的血糖调节和胰岛素抵抗均较基线水平有同等程度改善（p < 0.05）。与基线相比（p < 0.05）以及与MET组相比（p < 0.05），罗格列酮/二甲双胍联合治疗使hsCRP、白细胞、脂联素、IL-6、收缩压和舒张压有显著改善。相比之下，二甲双胍单药治疗与RSG+MET组相比，显著降低了BMI（p < 0.001）、总胆固醇（p = 0.012）和低密度脂蛋白（p = 0.020）水平。重要的是，RSG+MET组（-0.96±0.75 ng/ml，p < 0.001）和MET组（-0.92±0.57 ng/ml，p = 0.001）血清内脏脂肪素浓度均较基线水平同等程度降低。上述内脏脂肪素变化与腰臀比、糖化血红蛋白、空腹血糖、HOMA-IR、胰岛素、IL-6（仅在RSG+MET组）和脂肪量的变化相关。在标准多元回归分析中，空腹血糖、糖化血红蛋白、HOMA-IR和胰岛素仍然是血清内脏脂肪素水平变化的独立决定因素（R² = 0.836，p = 0.004）。
罗格列酮/二甲双胍联合治疗和二甲双胍单药治疗均通过调节血糖和胰岛素敏感性降低血清内脏脂肪素水平，而它们对初治T2DM患者的脂联素、IL-6和其他心血管危险因素有不同影响。
