肝硬化患者胰岛素抵抗的临床分析

doi:10.3969/j.issn.1674-8115.2023.02.007

摘要/Abstract

摘要：

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, 胰岛素抵抗, 胰岛素抵抗指数, 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.

Key words: liver cirrhosis, insulin resistance, homeostatic model assessment-insulin resistance (HOMA-IR), Child-Pugh classification

中图分类号:

R657.3

石翠翠, 张洁, 黄鹤鸣, 桑玉尔, 李光明. 肝硬化患者胰岛素抵抗的临床分析[J]. 上海交通大学学报（医学版）, 2023, 43(2): 188-193.

SHI Cuicui, ZHANG Jie, HUANG Heming, SANG Yuer, LI Guangming. Clinical analysis of insulin resistance in liver cirrhosis patients[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 188-193.

图/表 3

参考文献 20

1	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.
2	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.
3	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.
4	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.
5	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.
6	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.
7	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.
8	PETERSEN M C, SHULMAN G I. Mechanisms of insulin action and insulin resistance[J]. Physiol Rev, 2018, 98(4): 2133-2223.
9	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.
10	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.
11	孙志梅, 齐亚娟. 胰岛素信号通路与胰岛素抵抗[J]. 世界最新医学信息文摘, 2019, 19(52): 62-63.
	SUN Z M, QI Y J.Insulin signaling pathway and insulin resistance[J].World's Latest Medical Information Digest, 2019, 19(52): 62-63.
12	HARDEEP S D, NAVIDA B, DEVINDER S M.Prevalence of insulin resistance in cirrhosis of liver[J]. Int J Adv Med, 2018, 5(2): 375.
13	GORAL V, ATALAY R, KUCUKONER M. Insulin resistance in liver cirrhosis[J]. Hepatogastroenterology, 2010, 57(98): 309-315.
14	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.
15	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.
16	中华医学会糖尿病学分会胰岛素抵抗学组(筹). 胰岛素抵抗评估方法和应用的专家指导意见[J]. 中华糖尿病杂志, 2018, 10(6): 377-385.
	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.
17	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.
18	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.
19	刘丽, 江颖仪, 刘景. 不同Child-Pugh分级慢性乙型肝炎肝硬化患者糖代谢、胰岛素分泌情况及其与炎症反应的相关性分析[J]. 临床肝胆病杂志, 2020, 36(2): 324-328.
	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.
20	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.

Item	IR ≤ 1.64 (n=117)	IR > 1.64 (n=91)	P value
Age/year	63.23±12.38	61.48±11.11	0.290
BMI/(kg·m^-2)	22.05±3.50	25.64±3.65	0.000
Male/n (%)	74 (63.25)	45 (49.45)	0.049
Smoke/n (%)	42 (35.90)	31 (34.07)	0.880
Alcohol/n (%)	29 (24.79)	22 (24.18)	>0.990
T2DM/n (%)	30 (25.64)	44 (48.35)	0.001
Hypertension/n (%)	28 (23.93)	29 (31.87)	0.210
Child-Pugh grade
Child-Pugh A/n(%)	47 (40.17)	49 (53.85)	0.070
Child-Pugh B /n(%)	43 (36.75)	32 (35.16)	0.880
Child-Pugh C/n(%)	27 (23.08)	10 (10.99)	0.028
Child-Pugh score	7.63±2.20	6.93±1.99	0.020
FBG/(mmol·L^-1)	5.44±1.71	7.58±3.24	0.000
HbA1c/%	5.43±1.02	6.54±2.31	0.000
Fasting insulin/(mIU·L^-1)	4.06±1.87	12.32±8.39	0.000
HOMA-IR	0.94±0.39	4.25±4.51	0.000
Complication
EVB/n(%)	51 (43.59)	40 (43.96)	>0.990
Ascites/n(%)	78 (66.67)	33 (36.26)	0.000
HE/n(%)	7 (5.98)	5 (5.49)	>0.990

Item	IR ≤ 1.64 (n=117)	IR > 1.64 (n=91)	P value
Age/year	63.23±12.38	61.48±11.11	0.290
BMI/(kg·m^-2)	22.05±3.50	25.64±3.65	0.000
Male/n (%)	74 (63.25)	45 (49.45)	0.049
Smoke/n (%)	42 (35.90)	31 (34.07)	0.880
Alcohol/n (%)	29 (24.79)	22 (24.18)	>0.990
T2DM/n (%)	30 (25.64)	44 (48.35)	0.001
Hypertension/n (%)	28 (23.93)	29 (31.87)	0.210
Child-Pugh grade
Child-Pugh A/n(%)	47 (40.17)	49 (53.85)	0.070
Child-Pugh B /n(%)	43 (36.75)	32 (35.16)	0.880
Child-Pugh C/n(%)	27 (23.08)	10 (10.99)	0.028
Child-Pugh score	7.63±2.20	6.93±1.99	0.020
FBG/(mmol·L^-1)	5.44±1.71	7.58±3.24	0.000
HbA1c/%	5.43±1.02	6.54±2.31	0.000
Fasting insulin/(mIU·L^-1)	4.06±1.87	12.32±8.39	0.000
HOMA-IR	0.94±0.39	4.25±4.51	0.000
Complication
EVB/n(%)	51 (43.59)	40 (43.96)	>0.990
Ascites/n(%)	78 (66.67)	33 (36.26)	0.000
HE/n(%)	7 (5.98)	5 (5.49)	>0.990

Item	Child-Pugh A (n=162)	Child-Pugh B (n=148)	Child-Pugh C (n=66)	P value
FBG/(mmol·L^-1)	6.59±2.82	6.79±2.88	4.98±1.26	0.002
HbA1c/%	5.98±1.41	5.69±1.17	5.45±2.27	0.350
Fasting insulin/(mIU·L^-1)	9.04±8.36	6.49±5.26	5.62±5.75	0.010
HOMA-IR	3.02±4.47	2.01±2.11	1.54±1.68	0.038

Item	Child-Pugh A (n=162)	Child-Pugh B (n=148)	Child-Pugh C (n=66)	P value
FBG/(mmol·L^-1)	6.59±2.82	6.79±2.88	4.98±1.26	0.002
HbA1c/%	5.98±1.41	5.69±1.17	5.45±2.27	0.350
Fasting insulin/(mIU·L^-1)	9.04±8.36	6.49±5.26	5.62±5.75	0.010
HOMA-IR	3.02±4.47	2.01±2.11	1.54±1.68	0.038

Item	Cryptogenic cirrhosis (n=71)	Cirrhosis of the other etiologies (n=305)	P value
FBG/(mmol·L^-1)	6.47±2.69	6.22±2.57	0.464
HbA1c/%	5.95±2.28	5.73±1.29	0.287
Fasting insulin/(mIU·L^-1)	6.69±5.66	7.95±7.34	0.277
HOMA-IR	2.25±3.09	2.43±3.51	0.746