肝硬化患者口服葡萄糖耐量试验临床意义及研究进展

doi:10.3969/j.issn.1672-5069.2019.03.035

摘要/Abstract

摘要： 肝脏和骨骼肌维持糖代谢。随着慢性肝病进展为肝硬化,肝功能恶化会导致糖代谢异常。因此,肝硬化患者常常伴有糖耐量异常和胰岛素抵抗,早期以餐后高血糖和高胰岛素血症为特征。一般而言,即使应用传统的空腹血糖或糖化血红蛋白水平标准,肝硬化伴有糖代谢异常患者往往被低估,因为他们中的多数表现出较低的空腹血糖水平或糖化血红蛋白水平,掩盖了其糖耐量减低的实情。因此,推荐使用口服葡萄糖耐量试验来评估出现空腹血糖正常的餐后高血糖患者。

关键词: 肝硬化, 糖尿病, 口服葡萄糖耐量试验, 进展

Abstract: The liver and skeletal muscles are responsible for maintaining glucose metabolism. As chronic liver disease progresses to cirrhosis,the liver disfunction leads to the deterioration of glucose metabolism. Consequently,impaired glucose tolerance（IGT） and insulin resistance（IR） are often observed in patients with liver cirrhosis. In early stage,the cirrhotics with hepatogenous diabetes is characterized by marked postprandial hyperglycemia and hyperinsulinemia. Generally,it is possible to underestimate IGT when using either the conventional fasting plasma glucose （FPG） criterion or hemoglobin A1c （HbA1c） levels because many of these patients show lower FPG or HbA1c levels,which might mask their IGT. In this circumstances,the oral glucose tolerance test is recommended to properly evaluate patients with normal FPG levels.

Key words: Liver cirrhosis, Diabetes, Glucose intolerance, Oral glucose tolerance test, Prognosis

张婷婷（综述）, 王煊（审校）. 肝硬化患者口服葡萄糖耐量试验临床意义及研究进展[J]. 实用肝脏病杂志, 2019, 22(3): 449-452.

Zhang Tingting, Wang Xuan. Clinical implications of oral glucose tolerance test in cirrhotic patients with hepatogenous diabetes[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 449-452.

参考文献

[1] Muting D,Wohlgemuth D,Dorsett R.Liver cirrhosis and diabetes mellitus. Geriatrics,1969,24(1):91-99.
[2] HickmanIJ,MacdonaldGA. Impact of diabetes on the severity of liver disease. Am J Med,2007,120(10):829-834.
[3] Falchuk KR,Fiske SC,Haggitt RC,et al.Pericentral hepatic fibrosis and intracellular hyalin in diabetes mellitus. Gastroenterology,1980,78(3):535-541.
[4] Nishida T,Tsuji S,Tsujii M,et al.Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis. Am J Gastroenterol,2006,101(1):70-75.
[5] Imano E,Nishida T,Shibata M,et al.Significance of oral glucose tolerance test for the diagnosis of diabetes mellitus in patients with liver cirrhosis. Intern Med,1999,38(11):918.
[6] Roden M,Bernroider E.Hepatic glucose metabolism in humans: its role in health and disease. Best Pract Res Clin Endocrinol Metab,2003,17(3):365-383.
[7] Sinacore DR,Gulve EA.The role of skeletal muscle in glucose transport,glucose homeostasis,and insulin resistance:implications for physical therapy. Phys Ther,1993,73(12):878-891.
[8] Krssak M,Brehm A,Bernroider E,et al.Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes,2004,53(12):3048-3056.
[9] Imano E,Kanda T,Nakatani Y,et al.Impaired splanchnic and peripheral glucose uptake in liver cirrhosis. J Hepatol,1999,31(3):469-473.
[10] Cavallo-Perin P,Cassader M,Bozzo C,et al.Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect. J Clin Invest,1985,75(5):1659-1665.
[11] Shmueli E,Walker M,Alberti G,et al.Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis. Hepatology,1993,18(1):86-95.
[12] Shanik MH,Xu Y,Skrha J,et al. Insulin resistance and hyperinsulinemia:is hyperinsulinemia the cart or the horse Diabetes Care,2008,31(Suppl 2):S262-S268.
[13] Huang JF,Dai CY,Hwang SJ,et al.Hepatitis C viremia increases the association with type 2 diabetes mellitus in a hepatitis B and C endemic area:an epidemiological link with virological implication. Am J Gastroenterol,2007,102(6):1237-1243.
[14] Shintani Y,Fujie H,Miyoshi H,et al.Hepatitis C virus infection and diabetes:direct involvement of the virus in the development of insulin resistance. Gastroenterology,2004,126(3):840-848.
[15] Pazienza V,Clément S,Pugnale P,et al.The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology,2007,45(5):1164-1171.
[16] Davuluri G,Krokowski D,Guan BJ,et al.Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of L-leucine in cirrhosis. J Hepatol,2016,65(5):929-937.
[17] Garcia-Compean D,Jaquez-Quintana JO,Gonzalez-Gonzalez JA, et al.Liver cirrhosis and diabetes:risk factors,pathophysiology,clinical implications and management. World J Gastroenterol,2009,15(3):280-288.
[18] Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care,1997,20(7):1183-1197.
[19] International Expert Committee.International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care,2009,32(7):1327-1334.
[20] Picón MJ,Murri M,Munoz A,et al.Hemoglobin A1c versus oral glucose tolerance test in postpartum diabetes screening. Diabetes Care,2012,35(8):1648-1653.
[21] Kanda T,Nakamura M,Iwasaki M,et al.Clinical significance of HbA1c,serum fructosamine and 1,5-AG in diabetic patients complicated with liver cirrhosis. J Jpn Diabetes Soc,1993,36:847-854.
[22] Panzer S,Kronik G,Lechner K,et al.Glycosylated hemoglobins (GHb):an index of red cell survival. Blood,1982,59(6):1348-1350.
[23] Koga M,Kasayama S,Kanehara H,et al.CLD (chronic liver diseases):HbA1C as a suitable indicator for estimation of mean plasma glucose in patients with chronic liver diseases. Diabetes Res Clin Pract,2008,81(2):258-262.
[24] Matsumoto N,Arase Y,Seko Y,et al.Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of <126 mg/dL. Hepatol Res,2012,42(6):558-563.
[25] Holstein A,Hinze S,Thiessen E,et al.Clinical implications of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol,2002,17(6):677-681.
[26] Jeon HK,Kim MY,Baik SK,et al.Hepatogenous diabetes in cirrhosis is related to portal pressure and variceal hemorrhage. Dig Dis Sci,2013,58(11):3335-3341.
[27] Fukui H,Saito H,Ueno Y,et al.Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol,2016,51(7):629-650.
[28] Merli M,Leonetti F,Riggio O,et al.Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology,1999,30(3):649-654.
[29] D’Amico G,Garcia-Tsao G,Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis:a systematic review of 118 studies. J Hepatol,2006,44(1):217-231.
[30] Krige JE,Kotze UK,Bornman PC,et al.Variceal recurrence,rebleeding,and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices. Ann Surg,2006,244(5):764-770.
[31] Zoppini G,Fedeli U,Gennaro N,et al.Mortality from chronic liver diseases in diabetes. Am J Gastroenterol,2014,109(7):1020-1025.
[32] Bianchi G,Marchesini G,Zoli M,et al.Prognostic significance of diabetes in patients with cirrhosis. Hepatology,1994,20(pt 1):119-125.
[33] Moreau R,Delègue P,Pessione F,et al.Clinical characteristics and outcome of patients with cirrhosis and refractory ascites. Liver Int,2004,24(5):457-464.
[34] García-Compeán D,Jáquez-Quintana JO, Lavalle-González FJ,et al.Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis. World J Gastroenterol,2014,20(22):7011-7018.
[35] Sangiovanni A,Prati GM,Fasani P,et al.The natural history of compensated cirrhosis due to hepatitis C virus:a 17-year cohort study of 214 patients. Hepatology,2006,43(6):1303-1310.
[36] Elkrief L,Rautou PE,Sarin S,et al.Diabetes mellitus in patients with cirrhosis:clinical implications and management. Liver Int,2016,36(7):936-948.
[37] Forner A,Llovet JM,Bruix J.Hepatocellular carcinoma. Lancet,2012,379(9822):1245-1255.
[38] Yang WS,Va P,Bray F,et al.The role of preexisting diabetes mellitus on hepatocellular carcinoma occurrence and prognosis:a Meta-analysis of prospective cohort studies. PLoS One,2011,6(12):e27326.
[39] Tsugane S,Inoue M.Insulin resistance and cancer:epidemiological evidence. Cancer Sci,2010,101(5):1073-1079.
[40] Veldt BJ,Chen W,Heathcote EJ,et al.Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatology,2008,47(6):1856-1862.
[41] Tung HD,Wang JH,Tseng PL,et al.Neither diabetes mellitus nor overweight is a risk factor for hepatocellular carcinoma in a dual HBV and HCV endemic area:community cross-sectional and case-control studies. Am J Gastroenterol,2010,105(3):624-631.
[42] Takahashi H,Mizuta T,Eguchi Y,et al.Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C. J Gastroenterol,2011,46(6):790-798.