目的·探讨肝硬化患者的胰岛素抵抗情况。方法·收集2013年1月—2017年12月于上海交通大学医学院附属新华医院住院的肝硬化患者的临床资料。回顾性分析肝硬化患者糖代谢指标，包括空腹血糖（fasting blood glucose，FBG）、糖化血红蛋白（glycosylated hemoglobin A1c，HbA1c）、空腹胰岛素、胰岛素抵抗指数（homeostasis model assessment-insulin resistance，HOMA-IR）；记录肝硬化患者主要并发症，包括食管胃底静脉曲张破裂出血（esophagogastric varices bleeding，EVB）、腹水和肝性脑病（hepatic encephalopathy，HE）。根据肝硬化患者的HOMA-IR，将肝硬化患者分无胰岛素抵抗组（IR≤1.64）和胰岛素抵抗组（IR>1.64），进行各项指标的组间比较。结果·研究共纳入376例肝硬化患者，其中Child-Pugh A级患者162例（43.09%）、B级148例（39.36%）、C级66例（17.55%）。肝硬化主要病因是乙型病毒性肝炎，占43.35%（163例）。376例肝硬化患者中，208例进行了空腹胰岛素水平检测；其中，无胰岛素抵抗组117例（56.25%），胰岛素抵抗组91例（43.75%）。胰岛素抵抗组肝硬化患者体质量指数（body mass index，BMI）显著高于无胰岛素抵抗组（P=0.000）；胰岛素抵抗组中2型糖尿病患者的比例亦高于无胰岛素抵抗组（P=0.001）。胰岛素抵抗组肝硬化患者的Child-Pugh分数（6.93±1.99）低于无胰岛素抵抗组（7.63±2.20），差异具有统计学意义（P=0.020）。胰岛素抵抗组中Child-Pugh C级的肝硬化患者所占比例显著低于无胰岛素抵抗组（P=0.028）。在肝硬化并发症方面，胰岛素抵抗组肝硬化患者并发腹水的比例（36.26%）显著低于无胰岛素抵抗组（66.67%），差异有统计学意义（P=0.000）。2组患者并发EVB和HE的比例比较，差异无统计学意义（P>0.05）。结论·肝硬化患者中近半数存在胰岛素抵抗；有胰岛素抵抗的肝硬化患者BMI偏高，Child C级患者比例较低，较少并发腹水。
关键词：肝硬化
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胰岛素抵抗
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胰岛素抵抗指数
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Child-Pugh分级
Abstract
Objective ·To investigate the insulin resistance in liver cirrhosis patients. Methods ·Patients with liver cirrhosis from Xinhua Hospital,Shanghai Jiao Tong University School of Medicine in 2013‒2017 were retrospectively assessed. Biochemical indexes, including fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), fasting insulin and homeostatic model assessment-insulin resistance (HOMA-IR), were collected. The complications of liver cirrhosis were recorded, including esophagogastric varices bleeding (EVB), ascites and hepatic encephalopathy (HE). According to HOMA-IR value, the liver cirrhosis patients were divided into non-insulin resistance group (IR≤1.64) and insulin resistance group (IR>1.64). Various indicators were compared between the two groups. Results ·A total of 376 patients with liver cirrhosis were included in this study. The proportions of Child-Pugh A, Child-Pugh B and Child-Pugh C were 162 (43.09%), 148 (39.36%), and 66 (17.55%), respectively. The main cause of liver cirrhosis was hepatitis B virus infection 163 (43.35%). Fasting insulin levels were measured in 208 of 376 liver cirrhosis patients. Among them, 117 patients (56.25%) had no insulin resistance and 91 patients (43.75%) had insulin resistance. The body mass index (BMI) of liver cirrhosis patients in the insulin resistance group was significantly higher than that in the non-insulin resistance group (P=0.000), and the prevalence of type 2 diabetes in the former was also higher (P=0.001). The scores of Child-Pugh in patients with liver cirrhosis in the insulin resistance group were lower than those in the non-insulin resistance group, and the difference in Child-Pugh score was statistically significant (6.93±1.99 vs 7.63±2.20, P=0.020). The proportion of Child-Pugh C grade in the insulin resistance group was significantly lower than that in the patients without insulin resistance (P=0.028). The prevalence of ascites in cirrhotic patients with insulin resistance was significantly lower than that in cirrhotic patients without insulin resistance (36.26% vs 66.67%, P=0.000). There was no significant difference in the prevalence of EVB and HE between the two groups (P>0.05). Conclusion ·Nearly half of patients with liver cirrhosis are associated with insulin resistance. Compared with no-insulin resistance patients, cirrhotic patients with insulin resistance have a higher BMI, lower percentage of Child-Pugh C, and fewer ascites prevalence.
SHI Cuicui, ZHANG Jie, HUANG Heming, SANG Yuer, LI Guangming. Clinical analysis of insulin resistance in liver cirrhosis patients. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2023, 43(2): 188-193 doi:10.3969/j.issn.1674-8115.2023.02.007
肝硬化患者出现糖尿病可能与胰岛素抵抗密切相关［6-7］。胰岛素抵抗是T2DM的一个重要发病机制，是各种原因导致的正常剂量的胰岛素作用于机体后产生的生物学效应低于预期水平，葡萄糖摄取和利用的效率下降，导致血糖升高，机体代偿性地分泌过多胰岛素，产生高胰岛素血症，以维持血糖的稳定［8］。胰岛素抵抗是肝脏脂肪变性的独立危险因素［9-10］。肝硬化患者存在胰岛素抵抗的可能机制包括：门静脉血流降低，胰岛素摄取减少，导致高胰岛素血症；肝细胞、肌肉细胞、脂肪细胞的胰岛素受体数量和亲和力下降，降低了外周胰岛素作用［11］。胰岛素抵抗指数（homeostasis model assessment-insulin resistance，HOMA-IR）是用于评价个体胰岛素抵抗水平的指标。国际上多项研究以HOMA-IR˃1.64为界，判断肝硬化患者是否存在胰岛素抵抗，即HOMA-IR˃1.64提示存在胰岛素抵抗［12］。
胰岛素抵抗组肝硬化患者发生EVB的比例与无胰岛素抵抗组接近，分别为43.96%和43.59%，差异无统计学意义（P>0.05）。胰岛素抵抗组肝硬化患者发生腹水的比例显著低于无胰岛素抵抗组（36.26% vs 66.67%，P=0.000）。2组患者发生HE的比例比较，差异无统计学意义（5.49% vs 5.98%，P>0.05）。
The study was designed by LI Guangming and SANG Yuer. The manuscript was drafted and revised by SHI Cuicui, SANG Yuer and LI Guangming. The data analysis was conducted by SHI Cuicui and SANG Yuer. ZHANG Jie, HUANG Heming and SHI Cuicui participated in the data collection. All the authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
CHAO L T, WU C F, SUNG F Y, et al. Insulin, glucose and hepatocellular carcinoma risk in male hepatitis B carriers: results from 17-year follow-up of a population-based cohort[J]. Carcinogenesis, 2011, 32(6): 876-881.
SINGAL A K, AYOOLA A E. Prevalence and factors affecting occurrence of type 2 diabetes mellitus in Saudi patients with chronic liver disease[J]. Saudi J Gastroenterol, 2008, 14(3): 118-121.
HUNG C H, WANG J H, HU T H, et al. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection[J]. World J Gastroenterol, 2010, 16(18): 2265-2271.
PANG Y, KARTSONAKI C, TURNBULL I, et al. Diabetes, plasma glucose, and incidence of fatty liver, cirrhosis, and liver cancer: a prospective study of 0.5 million people[J]. Hepatology, 2018, 68(4): 1308-1318.
LIU T L, TROGDON J, WEINBERGER M, et al. Diabetes is associated with clinical decompensation events in patients with cirrhosis[J]. Dig Dis Sci, 2016, 61(11): 3335-3345.
ANTY R, ANTY R, IANNELLI A, et al. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients[J]. Aliment Pharmacol Ther, 2010, 32(11/12): 1315-1322.
BHAGAT V, MINDIKOGLU A L, NUDO C G, et al. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease[J]. Liver Transpl, 2009, 15(12): 1814-1820.
ESLAM M, SANYAL A J, GEORGE J, et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014.e1.
KITADE H, CHEN G, NI Y, et al. Nonalcoholic fatty liver disease and insulin resistance: new insights and potential new treatments[J]. Nutrients, 2017, 9(4): E387.
YAGMUR E, WEISKIRCHEN R, GRESSNER A M, et al. Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4[J]. Diabetes Care, 2007, 30(5): 1168-1172.
GHARAVI A, HAJAGHA M A, ZIAEE A, et al. Investigation of insulin resistance in patients with liver cirrhosis and its relationship with severity of disease[J].J Qazvin Univ Med Sci, 2008, 12(1): 27-34.
Insulin Resistance Group of Diabetics Branch of Chinese Medical Association. Expert guidance on methods and application of insulin resistance assessment[J].Chinese Journal of Diabetes,2018,10(6):377-385.
PETTA S, CAMMÀ C, DI MARCO V, et al. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection[J]. Liver Int, 2011, 31(4): 507-515.
GUO C H, SUN T T, WENG X D, et al. The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis[J]. Int J Clin Exp Pathol, 2015, 8(10): 13381-13386.
LIU L, JIANG Y Y, LIU J.Glucose metabolism and insulin secretion in patients with chronic hepatitis B cirrhosis of different Child-Pugh grades and their association with inflammatory response[J].Journal of Clinical Hepatobiliary Disease, 2020, 36(2): 324-328.
ALSEBAEY A, ELHELBAWY M. Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C[J]. Trop Doct, 2019, 49(4): 281-285.
