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糖耐量受损和糖尿病肝硬化患者血浆细胞因子水平失衡:一项前瞻性研究。

Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study.

作者信息

García-Compeán Diego, Jáquez-Quintana Joel O, Lavalle-González Fernando J, González-González José A, Maldonado-Garza Héctor J, Villarreal-Pérez Jesús Z

机构信息

Gastroenterology Service Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.

Endocrinology Service, Department of Internal Medicine, University Hospital "Dr. José E. González" and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.

出版信息

Ann Hepatol. 2014 Jul-Aug;13(4):403-10.

PMID:24927611
Abstract

AIMS

To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM).

MATERIAL AND METHODS

We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF- α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-β1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMA2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests.

RESULTS

Significantly higher sTNF-R1 and lower TGF-β1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found.

CONCLUSIONS

IGT and DM were associated with abnormalities of sTNF-R1 and TGF-β1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1 and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process.

摘要

目的

确定肝硬化(LC)合并糖耐量受损(IGT)或糖尿病(DM)患者的促炎、促纤维化和抗纤维化细胞因子的血浆水平是否失衡。

材料与方法

我们从100例空腹血糖(FPG)水平正常的LC患者中随机选取54例。根据口服葡萄糖耐量试验(OGTT)结果分为三组:18例正常,18例IGT,18例DM。检测细胞因子的血浆水平:肿瘤坏死因子-α(TNF-α)、可溶性肿瘤坏死因子受体1(sTNF-R1)、瘦素、转化生长因子-β1(TGF-β1)和肝细胞生长因子(HGF)。同时,测定空腹血浆胰岛素(FPI)水平并计算HOMA2-IR。将结果与18例无肝病和DM的对照组进行比较。采用非参数检验进行组间比较。

结果

与对照组相比,IGT和DM患者的sTNF-R1显著升高,TGF-β1显著降低。瘦素、HGF和TNF-α水平无显著差异。根据Child-Pugh分类,与A组相比,B组或C组的所有细胞因子水平均受损。发现sTNF-R1与HOMA2-IR之间以及瘦素与HOMA2-IR之间呈正相关。

结论

与非肝硬化对照组相比,IGT和DM与sTNF-R1和TGF-β1异常有关。在肝硬化患者中,晚期肝病中所有细胞因子的损伤更为明显。最后,sTNF-R1和瘦素与胰岛素抵抗(IR)相关。这些发现表明,IGT和DM可能与肝脏炎症过程有因果关系。

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