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胰高血糖素样肽-1类似物利拉鲁肽可改善患有多囊卵巢综合征和非酒精性脂肪性肝病的肥胖女性的肝纤维化标志物。

Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease.

作者信息

Kahal H, Abouda G, Rigby A S, Coady A M, Kilpatrick E S, Atkin S L

机构信息

Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, UK; Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Hull, UK.

出版信息

Clin Endocrinol (Oxf). 2014 Oct;81(4):523-8. doi: 10.1111/cen.12369. Epub 2013 Dec 12.

Abstract

INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) has been linked to polycystic ovary syndrome (PCOS) and carries an increased risk of liver cirrhosis. Procollagen type 3 amino-terminal peptide (PIIINP) is an independent predictor of liver cirrhosis.

OBJECTIVE

To assess whether 6-month treatment with GLP-1 analogue, liraglutide, improves markers of liver fibrosis.

DESIGN

A case-control study comparing women with PCOS to age- and weight-matched controls. PCOS was diagnosed according to the Rotterdam criteria. All participants underwent liver function tests and liver ultrasound scan to assess for fatty infiltration. Serum marker for liver fibrosis, PIIINP, was measured at baseline and after 6-month treatment with liraglutide 1·8 mg od.

RESULTS

Nineteen women with PCOS and 17 controls were recruited, age 32·8 ± 7·2 vs 33·5 ± 6·7 years and weight 100·9 ± 16·7 vs 99·3 ± 14·7 kg, respectively. At baseline, the PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nm (P = 0·01), HOMA-IR 5·1 ± 2·6 vs 3·5 ± 1·3 (P = 0·03), AST 22·4 ± 5·2 vs 18·8 ± 3·4 u/l (P = 0·04), PIIINP 4·4 ± 0·8 vs 3·5 ± 0·8 ug/ml (P = 0·01) and NAFLD seven (35%) vs none (P = 0·005), respectively. Twenty-five (69%) participants completed the study (13 PCOS, 12 controls). Following treatment, weight was reduced by 3·0 ± 4·2 kg (P = 0·01) and 3·8 ± 3·4 kg (P = 0·001), respectively. Similarly, HOMA-IR, hsCRP, triglycerides and urinary isoprostane significantly reduced in both groups. PIIINP significantly reduced the in PCOS group 4·4 ± 0·8 vs 3·7 ± 0·9 ug/ml (P < 0·01), but not in controls 3·5 ± 0·8 vs 3·2 ± 0·7 ug/ml (P = 0·08).

CONCLUSIONS

Treatment with liraglutide, and/or associated weight loss, significantly reduced PIIINP levels in obese women with PCOS. This may be an additional beneficial factor when considering the use of liraglutide in women with PCOS, obesity and NAFLD.

摘要

引言

非酒精性脂肪性肝病(NAFLD)与多囊卵巢综合征(PCOS)相关,且肝硬化风险增加。Ⅲ型前胶原氨基端肽(PIIINP)是肝硬化的独立预测指标。

目的

评估使用胰高血糖素样肽-1(GLP-1)类似物利拉鲁肽治疗6个月是否能改善肝纤维化指标。

设计

一项病例对照研究,将PCOS女性与年龄和体重匹配的对照进行比较。PCOS根据鹿特丹标准诊断。所有参与者均接受肝功能检查和肝脏超声扫描以评估脂肪浸润情况。在基线时以及使用1.8mg每日一次的利拉鲁肽治疗6个月后,测量肝纤维化血清标志物PIIINP。

结果

招募了19例PCOS女性和17例对照,年龄分别为32.8±7.2岁和33.5±6.7岁,体重分别为100.9±16.7kg和99.3±14.7kg。基线时,PCOS组的睾酮水平更高,分别为1.2±0.3与0.9±0.3nmol/L(P=0.01),胰岛素抵抗指数(HOMA-IR)为5.1±2.6与3.5±1.3(P=0.03),谷草转氨酶(AST)为22.4±5.2与18.8±3.4U/L(P=0.04),PIIINP为4.4±0.8与3.5±0.8μg/ml(P=0.01),NAFLD患者分别为7例(35%)与0例(P=0.005)。25例(69%)参与者完成了研究(13例PCOS患者,12例对照)。治疗后,体重分别减轻了3.0±4.2kg(P=0.01)和3.8±3.4kg(P=0.001)。同样,两组的HOMA-IR、高敏C反应蛋白(hsCRP)、甘油三酯和尿异前列腺素均显著降低。PCOS组的PIIINP显著降低,从4.4±0.8μg/ml降至3.7±0.9μg/ml(P<0.01),而对照组未显著降低,从3.5±0.8μg/ml降至3.2±0.7μg/ml(P=0.08)。

结论

利拉鲁肽治疗和/或相关体重减轻显著降低了肥胖PCOS女性的PIIINP水平。在考虑将利拉鲁肽用于患有PCOS、肥胖和NAFLD的女性时,这可能是一个额外的有益因素。

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