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利拉鲁肽对2型糖尿病患者脂肪细胞因子、胰岛素敏感性参数及心血管风险生物标志物的有益影响:一项前瞻性研究。

Beneficial effects of liraglutide on adipocytokines, insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: a prospective study.

作者信息

Díaz-Soto Gonzalo, de Luis Daniel Antonio, Conde-Vicente Rosa, Izaola-Jauregui Olatz, Ramos Carmen, Romero Enrique

机构信息

Endocrinology and Nutrition Service, Universitary Hospital of Valladolid, IEN-University of Valladolid, Spain.

Endocrinology and Nutrition Service, Universitary Hospital of Valladolid, IEN-University of Valladolid, Spain; Unit of Investigation, Hospital Rio Hortega, IEN-University of Valladolid, Spain.

出版信息

Diabetes Res Clin Pract. 2014 Apr;104(1):92-6. doi: 10.1016/j.diabres.2014.01.019. Epub 2014 Jan 25.

Abstract

AIMS

To evaluate the effects of liraglutide after 14 weeks of treatment on serum adipokines, insulin resistance index and cardiovascular risk biomarkers in overweight or obese T2DM patients unable to achieve glycemic control with metformin alone or in association with a sulfonylurea in daily clinical practice.

METHODS

Prospective study in 59 consecutive overweight or obese (BMI≥25kg/m(2)) T2DM patients unable to achieve glycemic control (HbA1c>7%, 53mmol/mol) with metformin alone or in association with sulfonylurea that require initiation of liraglutide in progressive dose increase up to 1.8mg/day subcutaneously. Weight, body composition, blood pressure, glucose, HbA1c, C-peptide, insulin, plasma lipids, adipokines (leptin, adiponectin, resistin and visfatin) as well as cardiovascular biomarkers (IL-6 and TNF-a) levels were measured fasting at baseline and 14 weeks after liraglutide initiation.

RESULTS

14 weeks of liraglutide treatment significantly reduced HbA1c, BMI and total body fat mass by 0.9%, 1.4kg/m(2) and 0.5% respectively. Statistically significant lower insulin resistance and higher insulin secretion was found by HOMA-IR 8.4 (1.6) vs 4.6 (0.9)molmIU/L(2) and HOMA-B 48.2 (9.0) vs 87.6 (16.3)μIU/mmol. Statistically significantly higher levels of visfatin 6.3 (2.1) vs 6.8 (2.1)ng/ml and resistin 3.6 (2.0) vs 4.3 (2.3)ng/ml were also observed after treatment. Baseline visfatin was negatively correlated with basal fasting plasma glucose r=-0.360 (p<0.05).

CONCLUSIONS

Liraglutide treatment for 14 weeks in daily clinical practice led to reduction of BMI and improvement of glucose control and insulin sensitivity and resistance parameters. Additionally, circulating levels of adipokines and pro-inflammatory factors could play an important role in GLP-1 treatment response.

摘要

目的

在日常临床实践中,评估利拉鲁肽治疗14周对单用二甲双胍或联合磺脲类药物治疗仍无法实现血糖控制的超重或肥胖2型糖尿病患者血清脂肪因子、胰岛素抵抗指数及心血管风险生物标志物的影响。

方法

对59例连续的超重或肥胖(BMI≥25kg/m²)2型糖尿病患者进行前瞻性研究,这些患者单用二甲双胍或联合磺脲类药物均无法实现血糖控制(糖化血红蛋白>7%,53mmol/mol),需要起始皮下注射利拉鲁肽并逐步增加剂量至1.8mg/天。在基线和利拉鲁肽起始治疗14周后,空腹测量体重、身体成分、血压、血糖、糖化血红蛋白、C肽、胰岛素、血脂、脂肪因子(瘦素、脂联素、抵抗素和内脂素)以及心血管生物标志物(白细胞介素-6和肿瘤坏死因子-α)水平。

结果

利拉鲁肽治疗14周后,糖化血红蛋白、BMI和全身脂肪量分别显著降低0.9%、1.4kg/m²和0.5%。通过稳态模型评估胰岛素抵抗(HOMA-IR)发现,胰岛素抵抗显著降低,胰岛素分泌增加,分别为8.4(1.6)与4.6(0.9)molmIU/L²,以及通过稳态模型评估β细胞功能(HOMA-β)为48.2(9.0)与87.6(16.3)μIU/mmol。治疗后还观察到内脂素水平显著升高,分别为6.3(2.1)与6.8(2.1)ng/ml,抵抗素水平为3.6(2.0)与4.3(2.3)ng/ml。基线内脂素与基础空腹血糖呈负相关,r=-0.360(p<0.05)。

结论

在日常临床实践中,利拉鲁肽治疗14周可降低BMI,改善血糖控制及胰岛素敏感性和抵抗参数。此外,脂肪因子和促炎因子的循环水平可能在胰高血糖素样肽-1治疗反应中起重要作用。

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