PDF icon Download PDF
Exp Clin Endocrinol Diabetes 2010; 118(2): 75-80
DOI: 10.1055/s-0029-1237360
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Visfatin (Nampt) and Ghrelin as Novel Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes

N. P. E. Kadoglou1 , 2 , N. Sailer1 , A. Moumtzouoglou3 , A. Kapelouzou2 , H. Tsanikidis1 , I. Vitta1 , C. Karkos4 , P. E. Karayannacos2 , T. Gerasimidis4 , C. D. Liapis5
  • 1First Department of Internal Medicine, “Hippokratio” General Hospital of Thessaloniki, Greece
  • 2Foundation of Biomedical Research, Center of Experimental Surgery, Academy of Athens, Greece
  • 3Laboratory of Radiology, “Hippokratio” General Hospital of Thessaloniki, Greece
  • 4Fifth Surgical Department, Aristotle University of Thessaloniki, Greece
  • 5Department of Vascular Surgery, Medical School, University of Athens, Greece
Further Information

Publication History

received 15.03.2009 first decision 24.06.2009

accepted 22.07.2009

Publication Date:
15 October 2009 (online)

Also available ateRef
   Permissions and Reprints
Preview

Abstract

Objective: Visfatin (nampt) and ghrelin are the most recently identified adipocytokines, but their role in atherosclerosis is poorly clarified. In our study we investigated their association with advanced carotid atherosclerosis and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).

Methods: 122 patients (50 males) with T2DM, aged 55–70 were enrolled. Sixty-four age- and sex-matched healthy individuals served as controls (group A). CIMT was assayed in all participants by ultrasound. Among diabetic patients, 47 appeared with carotid plaques (group B), while 75 without plaques (group C). Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), fibrinogen, nampt and ghrelin were measured.

Results: Diabetic patients had a higher mean-CIMT, increased body-mass index, worse lipid profile, elevated blood pressure and higher levels of white blood cells count, nampt and hsCRP with respect to controls (p<0.01). Among diabetic patients, groups B and C were comparable in anthropometric, glycemic and lipid parameters. Serum nampt was significantly higher in group B rather than in groups A and C (p<0.05). On the other hand, ghrelin levels were considerably lower only in diabetic patients with carotid atherosclerosis compared with healthy individuals. In univariate analysis, mean-CIMT correlated with age (r=0.312; p=0.003), nampt (r=0.341; p<0.001) and ghrelin (r=−0.421; p=0.002) and the latter associations remained significant in multiple regression analysis.

Conclusions: High nampt and low ghrelin serum levels are significantly associated with advanced carotid atherosclerosis in patients with T2DM. Moreover these adipocytokines are independently associated with CIMT, implicating their role as novel atherosclerotic biomarkers and providing another important link between adiposity and atherosclerosis.

Key words

visfatin (nampt) - ghrelin - carotid intima-media thickness - atherosclerosis - type 2 diabetes - adiposity

References

  • 1 Bastard JP, Maachi M, Lagathu C. et al . Recent advances in the relationship between obesity, inflammation, and insulin resistance.  Eur Cytokine Netw. 2006;  17 4-12 Superfluous sentence 
    Search in Google Scholar
  • 2 Beauloye V, Zech F, Tran HT. et al . Determinants of early atherosclerosis in obese children and adolescents.  J Clin Endocrinol Metab. 2007;  92 3025-3032
    Search in Google Scholar
  • 3 Berndt J, Klöting N, Kralisch S. et al . Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.  Diabetes. 2005;  54 2911-2916
    Search in Google Scholar
  • 4 Blüher M. Adipose tissue dysfunction in obesity.  Exp Clin Endocrinol Diabetes. 2009;  117 241-250
    Search in Google Scholar
  • 5 Chen MP, Chung FM, Chang DM. et al . Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2006;  91 295-299
    Search in Google Scholar
  • 6 Clodi M, Resl M, Stelzeneder D. et al . Interactions of glucose metabolism and chronic heart failure.  Exp Clin Endocrinol Diabetes. 2009;  117 99-106
    Search in Google Scholar
  • 7 Dahl TB, Yndestad A, Skjelland M. et al . Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.  Circulation. 2007;  115 972-980
    Search in Google Scholar
  • 8 Despres JP. Abdominal obesity: the most prevalent cause of the metabolic syndrome and related cardiometaboli risk.  Eur Heart J. 2006;  Suppl 6 B4-B12
    Search in Google Scholar
  • 9 Dixit VD, Schaffer EM, Pyle RS. et al . Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.  J Clin Invest. 2004;  114 57-66
    Search in Google Scholar
  • 10 Dogru T, Sonmez A, Tasci I. et al . Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.  Diabetes Res Clin Pract. 2007;  76 24-29
    Search in Google Scholar
  • 11 Fukuhara A, Matsuda M, Nishizawa M. et al . Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.  Science. 2005;  307 426-430
    Search in Google Scholar
  • 12 García EA, Korbonits M. Ghrelin and cardiovascular health.  Curr Opin Pharmacol. 2006;  6 142-147
    Search in Google Scholar
  • 13 Genís BB, Granada ML, Alonso N. et al . Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation.  Transplantation. 2007;  84 1248-1254
    Search in Google Scholar
  • 14 Henry RR. Insulin resistance: From predisposing factor to therapeutic target in type 2 diabetes.  Clin Ther. 2003;  25 ((Suppl B)) B47-B63
    Search in Google Scholar
  • 15 Kathiresan S, Larson MG, Keyes MJ. et al . Assessment by cardiovascular magnetic resonance, electron beam computed tomography, and carotid ultrasonography of the distribution of subclinical atherosclerosis across Framingham risk strata.  Am J Cardiol. 2007;  99 310-314
    Search in Google Scholar
  • 16 Katugampola SD, Pallikaros Z, Davenport AP. [125I-His(9)]-ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue: up-regulation of receptors with athersclerosis.  Br J Pharmacol. 2001;  134 143-149
    Search in Google Scholar
  • 17 Kojima M, Hosoda H, Date Y. et al . Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
    Search in Google Scholar
  • 18 Korbonits M, Goldstone AP, Gueorguiev M. et al . Ghrelin – a hormone with multiple functions.  Front Neuroendocrinol. 2004;  25 27-68
    Search in Google Scholar
  • 19 Kotani K, Sakane N, Saiga K. et al . Serum ghrelin and carotid atherosclerosis in older Japanese people with metabolic syndrome.  Arch Med Res. 2006;  37 903-906
    Search in Google Scholar
  • 20 Lopez-Bermejo A, Chico-Julia B, Fernandez-Balsells M. et al . Serum visfatin increases with progressive β-cell deterioration.  Diabetes. 2006;  55 2871-2875
    Search in Google Scholar
  • 21 Pöykkö SM, Kellokoski E, Ukkola O. et al . Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males.  J Intern Med. 2006;  260 43-52
    Search in Google Scholar
  • 22 Pöykkö SM, Kellokoski E, Horkko S. et al . Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes.  Diabetes. 2003;  52 2546-2553
    Search in Google Scholar
  • 23 Roman MJ, Naqvi TZ, Gardin JM. et al . American society of echocardiography report. Clinical application of non-invasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology.  Vasc Med. 2006;  11 201-211
    Search in Google Scholar
  • 24 Ross R. Atherosclerosis – an inflammatory disease.  N Engl J Med. 1999;  340 115-126
    Search in Google Scholar
  • 25 Russell M, Fleg JL, Galloway WJ. et al . Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes – the Stop Atherosclerosis in Native Diabetics Study (SANDS).  Am Heart J. 2006;  152 867-875
    Search in Google Scholar
  • 26 Salonen R, Seppänen K, Rauramaa R. et al . Prevalence of carotid atherosclerosis and serum cholesterol levels in eastern Finland.  Arteriosclerosis. 1988;  8 788-792
    Search in Google Scholar
  • 27 Sandeep S, Velmurugan K, Deepa R. et al . Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians.  Metabolism. 2007;  56 565-570
    Search in Google Scholar
  • 28 Sepulveda JL, Mehta JL. C-reactive protein and cardiovascular disease: a critical appraisal.  Curr Opin Cardiol. 2005;  20 407-416
    Search in Google Scholar
  • 29 Skilton MR, Celermajer DS. The effects of obesity-related peptides on the vasculature.  Curr Vasc Pharmacol. 2006;  4 79-85
    Search in Google Scholar
  • 30 Ueno H, Shiiya T, Mizuta M. et al . Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics.  Endocr J. 2007;  54 895-902
    Search in Google Scholar
  • 31 Ukkola O, Poykko S, Paivansalo M. et al . Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and early atherosclerosis.  Ann Med. 2008;  40 465-473
    Search in Google Scholar
  • 32 Varma V, Yao-Borengasser A, Rasouli N. et al . Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation.  J Clin Endocrinol Metab. 2007;  92 666-672
    Search in Google Scholar
  • 33 Yano Y, Toshinai K, Inokuchi T. et al . Plasma des-acyl ghrelin, but not plasma HMW adiponectin, is a useful cardiometabolic marker for predicting atherosclerosis in elderly hypertensive patients.  Atherosclerosis. 2009;  590-594
    Search in Google Scholar
  • 34 Zhong M, Tan HW, Gong HP. et al . Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis.  Clin Endocrinol (Oxf). 2008;  69 878-884
    Search in Google Scholar

1 The ClinicalTrials.gov Identifi er is: NCT00306176

Correspondence

N. P. E. Kadoglou

124 Vosporou str

GR-54454 Thessaloniki

Greece

Phone: +30/23/1090 51 78

Fax: +30/23/1090 51 78

Email: nikoskad@yahoo.com

Email: nkado@med.uoa.gr