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罗格列酮和二甲双胍对炎症标志物及脂肪因子的影响:白细胞介素-18降低是2型糖尿病患者稳态模型评估-胰岛素抵抗指数改善的独立因素。

Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus.

作者信息

Kim Hyeong Jin, Kang Eun Seok, Kim Dae Jung, Kim So Hun, Ahn Chul Woo, Cha Bong Soo, Nam Moonsuk, Chung Choon Hee, Lee Kwan Woo, Nam Chung Mo, Lee Hyun Chul

机构信息

Division of Endocrinology, Department of Internal Medicine, Kwandong University College of Medicine, Myongji Hospital, Koyang, Korea.

出版信息

Clin Endocrinol (Oxf). 2007 Feb;66(2):282-9. doi: 10.1111/j.1365-2265.2006.02723.x.

Abstract

OBJECTIVE

We examined the individual pharmacological effects of the addition of rosiglitazone and metformin to glimepiride on inflammatory markers and adipokines in patients with type 2 diabetes mellitus. We analysed the relationships between these variables, the measurements of insulin sensitivity and beta-cell function in patients treated with rosiglitazone plus glimepiride.

DESIGN AND PATIENTS

One hundred twenty (120) patients with type 2 diabetes mellitus were randomized and treated with glimepiride plus rosiglitazone or glimepiride plus metformin for 12 weeks. The plasma concentrations of the inflammatory markers and adipokines were measured at baseline and after 12 weeks.

MEASUREMENTS

Markers of insulin sensitivity and beta-cell function were determined by the quantitative insulin sensitivity check index (QUICKI) and the homeostasis model assessment of beta-cell function (HOMA-beta), respectively. Plasma concentrations of adiponectin were measured by radioimmunoassay. Plasma concentrations of resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-18 (IL-18) were measured using ELISA.

RESULTS

Improvements in fasting insulin level, QUICKI and HOMA-beta were noted in the rosiglitazone-treated group. Only the QUICKI value improved in the metformin-treated group. Adiponectin concentrations significantly increased in the rosiglitazone-treated group after 12 weeks. Significant decreases in resistin, C-reactive protein, TNF-alpha, IL-6 and IL-18 were seen in the rosiglitazone-treated patients but not in the metformin-treated patients. The independent risk factor for the HOMA-beta change according to stepwise multivariate regression analysis was a change in IL-18.

CONCLUSIONS

Rosiglitazone, but not metformin, improved the plasma concentrations of inflammatory markers and adipokines in patients with type 2 diabetes mellitus. A decrease in IL-18 is an independent factor for the improvement of HOMA-beta in type 2 diabetes mellitus.

摘要

目的

我们研究了在2型糖尿病患者中,罗格列酮和二甲双胍分别与格列美脲联用对炎症标志物和脂肪因子的个体药理作用。我们分析了这些变量之间的关系,以及罗格列酮联合格列美脲治疗患者的胰岛素敏感性和β细胞功能测量值之间的关系。

设计与患者

120例2型糖尿病患者被随机分组,接受格列美脲加罗格列酮或格列美脲加二甲双胍治疗12周。在基线和12周后测量炎症标志物和脂肪因子的血浆浓度。

测量指标

胰岛素敏感性标志物和β细胞功能分别通过定量胰岛素敏感性检查指数(QUICKI)和β细胞功能的稳态模型评估(HOMA-β)来确定。脂联素的血浆浓度通过放射免疫分析法测量。抵抗素、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-18(IL-18)的血浆浓度使用酶联免疫吸附测定法测量。

结果

罗格列酮治疗组的空腹胰岛素水平、QUICKI和HOMA-β有所改善。二甲双胍治疗组仅QUICKI值有所改善。罗格列酮治疗组在12周后脂联素浓度显著升高。罗格列酮治疗的患者中抵抗素、C反应蛋白、TNF-α、IL-6和IL-18显著降低,而二甲双胍治疗的患者中未出现这种情况。根据逐步多变量回归分析,HOMA-β变化的独立危险因素是IL-18的变化。

结论

罗格列酮而非二甲双胍改善了2型糖尿病患者炎症标志物和脂肪因子的血浆浓度。IL-18的降低是2型糖尿病患者HOMA-β改善的独立因素。

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