期刊论文详细信息
Journal of Diabetes & Metabolic Disorders
Diagnostic accuracy of acyl-ghrelin and it association with non-alcoholic fatty liver disease in type 2 diabetic patients
Petro Bodnar1  Nazarii Kobyliak1  Galyna Mykhalchyshyn1 
[1] Bogomolets National Medical University, T. Shevchenko blvd, 13, Kyiv, 01601, Ukraine
关键词: Type 2 diabetes;    Acyl-ghrelin;    Non-alcoholic fatty liver disease;   
Others  :  1212322
DOI  :  10.1186/s40200-015-0170-1
 received in 2014-02-12, accepted in 2015-05-10,  发布年份 2015
PDF
【 摘 要 】

Background

Ghrelin is a hormone produced mainly by the cells lining the fundus of the stomach, which is involved in regulation of lipid and glucose metabolism. Two major forms of ghrelin can be found in circulation: an acylated form, and non-acylated form. Serum acyl-ghrelin (AG) concentration is significantly increased in patients with visceral obesity and insulin resistance. This study was conducted to evaluate changes in serum AG levels, its diagnostic accuracy and association with NAFLD in patients with type two diabetes (T2D).

Methods

In this cross-sectional study, 91 T2D patients, age of 40–80 years, were included. All patients were divided into 3 groups. The control group included 28 T2D patients without NAFLD. The main group included 63 T2D patients with NAFLD, which was divided in 2 subgroups depending on transaminase levels: normal (n = 37) and elevated (n = 26) transaminases group. To assess the diagnostic accuracy of AG for NAFLD we used ROC-analysis.

Results

We observed 1.5 (p = 0.016) and 2.5 (p < 0.001) fold increasing of serum AG levels in patients with NAFLD and normal or elevated transaminases compared to control groups. In multivariate logistic regression analysis high AG level was an independent, from transaminases activity, triglycerides (OR 1.791; 95 % CI 1.162–2.759; p = 0.008) and degree of IR (OR 1.599; 95 % CI 1.019–2.508; p = 0.044) predictor that associated with NAFLD. When serum AG used as non-invasive marker for NAFLD detection AUROC was 0.835 (95 % CI 0.752–0.918, p < 0.001). The cut-off value was >0.52 ng/ml, with sensitivity, specificity, PPV and NPV – 60.3 %, 92.8 %, 95.0 %, 50.9 % respectively. For distinguishing patients with NAFLD and elevated transaminases from patients with NAFLD and normal values AG was less effective.

Conclusions

Our study has demonstrated that elevated AG level were associated with NAFLD. Patients with elevated transaminases had significantly higher AG levels. An increase of AG over 0.52 ng/ml can be used as a diagnostic marker for NAFLD detection in patients with T2D.

【 授权许可】

   
2015 Mykhalchyshyn et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150614090659454.pdf 549KB PDF download
Fig. 2. 17KB Image download
Fig. 1. 16KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】
  • [1]Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Järvinen H, Svegliati-Baroni G. From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 2010; 42:320-30.
  • [2]Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatol. 2006; 43:99-112.
  • [3]Weston SR, Leyden W, Murphy R, Bass NM, Bell BP, Manos MM. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatol. 2005; 41:372-9.
  • [4]Kobyliak N, Abenavoli L. The role of liver biopsy to assess non-alcoholic fatty liver disease. Rev Recent Clin Trials. 2014; 9:159-69.
  • [5]Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of nonalcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011; 43:617-49.
  • [6]Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterol. 1998; 114:842-5.
  • [7]Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115:1343-51.
  • [8]Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK et al.. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterol. 2001; 120:1183-92.
  • [9]Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M et al.. Dysfunctional very-lowdensity lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatol. 2009; 50:772-80.
  • [10]Musso G, Gambino R, Cassader M. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Prog Lipid Res. 2009; 48:1-26.
  • [11]Schwarz JM, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr. 2003; 77:43-50.
  • [12]Schadinger SE, Bucher NL, Schreiber BM, Farmer SR. PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab. 2005; 288:1195-205.
  • [13]Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem. 1999; 274:30028-32.
  • [14]Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone releasing acylated peptide from stomach. Nature. 1999; 402:656-60.
  • [15]Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG et al.. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinol. 2004; 145:2607-12.
  • [16]Tscho¨p M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001; 50:707-9.
  • [17]Dezaki K, Hosoda H, Kakei M, Hashiguchi S, Watanabe M, Kangawa K et al.. Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes. 2004; 53:3142-51.
  • [18]Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ et al.. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab. 2005; 90:1055-60.
  • [19]Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes. 2002; 51:3408-11.
  • [20]Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M et al.. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab. 2004; 89:3062-5.
  • [21]Gauna C, Meyler FM, Janssen JA, Delhanty PJ, Abribat T, van Koetsveld P et al.. Administration of acylated ghrelin reduces insulin sensitivity, whereas the combination of acylated plus unacylated ghrelin strongly improves insulin sensitivity. J Clin Endocrinol Metab. 2004; 89:5035-42.
  • [22]Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K et al.. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatol. 2012; 55:2005-23.
  • [23]Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18:499-502.
  • [24]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetol. 1985; 28:412-9.
  • [25]Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K et al.. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005; 143:722-8.
  • [26]Webb M, Yeshua H, Zelber-Sagi S, Santo E, Brazowski E, Halpern Z et al.. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol. 2009; 192:909-14.
  • [27]Borges VF, Diniz AL, Cotrim HP, Rocha HL, Andrade NB. Sonographic hepatorenal ratio: a noninvasive method to diagnose nonalcoholic steatosis. J Clin Ultrasound. 2013; 41:18-25.
  • [28]Marchesini G, Pagotto U, Bugianesi E, De Iasio R, Manini R, Vanni E et al.. Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance. J Clin Endocrinol Metab. 2003; 88:5674-9.
  • [29]Tacke F, Brabant G, Kruck E, Horn R, Schöffski P, Hecker H et al.. Ghrelin in chronic liver disease. J Hepatol. 2003; 38:447-54.
  • [30]Estep M, Abawi M, Jarrar M, Wang L, Stepanova M, Elariny H et al.. Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease. Obes Surg. 2011; 21:1750-7.
  • [31]Gutierrez-Grobe Y, Villalobos-Blasquez I, Sánchez-Lara K, Villa AR, Ponciano-Rodríguez G, Ramos MH et al.. High ghrelin and obestatin levels and low risk of developing fatty liver. Ann Hepatol. 2010; 9:52-7.
  • [32]Aydin S. Is it appropriate to study blood ghrelin and obestatin in non-alcoholic fatty liver disease (NAFLD) without using protease inhibitors? Ann Hepatol. 2012; 11:145-6.
  • [33]Rodríguez A, Gómez-Ambrosi J, Catalán V, Gil MJ, Becerril S, Sáinz N et al.. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes (Lond). 2009; 53:541-52.
  • [34]Kobyliak N, Mykhalchyshyn G, Bodnar P. Relationships between acylated ghrelin and parameters of metabolic profile in patients with non-alcoholic fatty liver disease depending on transaminases activity. Res J Pharm Biol Chem Sci. 2015; 6:1097-105.
  • [35]Nishi Y, Hiejima H, Hosoda H, Kaiya H, Mori K, Fukue Y et al.. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinol. 2005; 146:2255-64.
  • [36]Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell. 2008; 132:387-96.
  文献评价指标  
  下载次数:10次 浏览次数:13次