Horm Metab Res 2007; 39(10): 764-768
DOI: 10.1055/s-2007-985867
Clinical Human

© Georg Thieme Verlag KG Stuttgart · New York

Visfatin: A Putative Biomarker for Metabolic Syndrome is not Influenced by Pioglitazone or Simvastatin Treatment in Nondiabetic Patients at Cardiovascular Risk - Results from the PIOSTAT Study

A. Pfützner 1 , 2 , M. Hanefeld 3 , G. Lübben 4 , M. M. Weber 5 , E. Karagiannis 4 , C. Köhler 3 , C. Hohberg 1 , T. Forst 1 , 5
  • 1Institute for Clinical Research and Development, Mainz, Germany
  • 2University of Applied Sciences, Rheinbach, Germany
  • 3GWT, Dresden, Germany
  • 4TAKEDA Pharma GmbH, Aachen, Germany
  • 5Johannes Gutenberg University, Department of Endocrinology, Mainz, Germany
Further Information

Publication History

received 29. 03. 2007

accepted 10. 07. 2007

Publication Date:
22 October 2007 (online)

Abstract

Objective: The aim of the study was to analyze the effect of pioglitazone (PIO) and simvastatin (SIMVA) on adiponectin and visfatin concentrations in nondiabetic patients with metabolic syndrome and increased risk for cardiovascular complications in a prospective randomized clinical trial.

Research Design and Methods: One-hundred twenty-five nondiabetic patients with increased cardiovascular risk [78 females, 47 males, age (mean±STD:58.6±7.8years, BMI:30.8±4.2(kg/m2] were included after randomization to PIO+lacebo, SIMVA+placebo, or PIO+SIMVA treatment for 3 months. At baseline and endpoint, measurements of HbA1c, glucose, insulin, LDL cholesterol, adiponectin and visfatin were performed. Insulin resistance was assessed by means of the HOMAIR-score.

Results: Improvement in the HOMAIR-score was observed with PIO and the combination, but not with SIMVA alone, which was accompanied by an increase in adiponectin with PIO treatment groups, but a decrease with SIMVA alone (baseline/endpoint: PIO: 14.0±8.2 mg/l/ 27.6± 14.5 mg/l, p<0.05; PIO+SIMVA: 11.7±10.0 mg/l/26.7±15.7 mg/l, p<0.05; SIMVA: 15.5±12.7 mg/l/ 11.6±7.0 mg/l, p<0.05). No change could be observed in the visfatin concentrations (PIO: 47.6±14.5 ng/ml/48.0±11.6 ng/ml, PIO+SIMVA: 45.1±10.9 ng/ml/47.9±10.1 ng/ml, SIMVA: 49.2± 13.4 ng/ml/52.1±16.7 ng/ml, n. s. in all cases).

Conclusions: Insulin resistance and/or cardiovascular risk indicators were not associated with visfatin levels. Regulation of visfatin secretion occurs through biochemical pathways independent from those influenced by pioglitazone or simvastatin.

References

  • 1 Rajala MW, Scherer PE. Minireview: The adipocyte - at the crossroads of energy homeostasis, inflammation, and atherosclerosis.  Endocrinology. 2003;  144 3765-3773
  • 2 Arner P. Insulin resistance in type 2 diabetes - role of adipokines.  Curr Mol Med. 2005;  5 333-339
  • 3 Schöndorf T, Maiworm A, Emission N, Forst T, Pfützner A. Biological background and role of adiponectin as marker for insulin resistance and cardiovascular risk.  Clin Lab. 2005;  51 489-494
  • 4 Thamer C, Haap M, Heller E, Joel L, Braun S, Tschritter O, Häring H, Fritsche A. Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes.  Horm Metab Res. 2006;  38 178-182
  • 5 Heliövaara MK, Strandberg TE, Karonen SL, Ebeling P. Association of serum adiponectin concentrations to lipid and glucose metabolism in healthy humans.  Horm Metab Res. 2006;  38 336-340
  • 6 Fantuzzi G. Adipose tissue, adipokines, and inflammation.  J Allergy Clin Immunol. 2005;  115 911-919
  • 7 Kershaw EE, Flier JS. Adipose tissue as an endocrine organ.  J Clin Endocrinol Metab. 2004;  89 2548-2556
  • 8 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K. et al . Visfatin: a protein secreted by visceral fat that minimcs the effects of insulin.  Science. 2005;  307 426-430
  • 9 Chen MP, Chung FM, Chang DM, Tsai JCR, Huang HF, Shin SJ, Lee YJ. Elevated plasma level of visfatin/pre-B cell colony enhancement factor in patients with type 2 diabetes.  J Clin Endocrinol Metab. 2006;  91 295-299
  • 10 Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R Milan G, Rossato M, Federspil G, Vettor R. Reduced plasma visfatin/pre B-cell colony enhancing factor in obesity is not related to insulin resistance in humans.  J Clin Endocrinol Metab. 2006;  91 3165-3170
  • 11 Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M. The release of the adipocytokine visfatin is regulated by glucose and insulin.  Diabetologia. 2006;  49 1909-1914
  • 12 Hanefeld M, Marx N, Pfützner A, Baurecht W, Lübben G, Karagiannis E, Stier U, Forst T. Anti-Inflammatory effect of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitive CRP: The PIOSTAT study.  J Am Coll Cardiol. 2007;  49 290-297
  • 13 Forst T, Pfützner A, Lübben G, Weber M, Marx N, Karagiannis E, Köhler C, Baurecht W, Hohberg C, Hanefeld M. Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk - the PIOSTAT Study.  Metabolism. 2007;  56 491-496
  • 14 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.  Diabetologia. 1985;  28 412-419
  • 15 Hedblad B, Nilsson P, Janzon L, Berglund G. Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmo, Sweden.  Diabet Med. 2000;  17 299-307
  • 16 Forst T, Hohberg C, Fuellert S, Lübben G, Konrad T, Löbig M, Weber MM, Sachara C, Gottschall V, Pfützner A. Pharmacological PPARγ stimulation in contrast to beta cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with type 2 diabetes.  Horm Metab Res. 2005;  37 521-527
  • 17 Pfützner A, Schöndorf T, Seidel D, Winkler K, Matthaei S, Hamann A, Forst T. Impact of rosiglitazone on β-cell function, insulin resistance and adiponektin concentrations - results from a double blind oral combination study with glimepiride.  Metabolism. 2006;  55 20-25
  • 18 Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes.  Diabetes. 2004;  53 2169-2176
  • 19 Yang B, Brown KK, Chen L, Carrick KM, Clifton LG, MacNulty JA, Winegar DA, Strum JC, Stimpson SA, Pahel GL. Serum adiponectin as a biomarker for in vivo PPARgamma activation and PPARgamma agonist-induced efficacy on insulin sensitization/lipid lowering in rats.  BMC Pharmacol. 2004;  4 23
  • 20 Hammarstedt A, Pihlajamäki J, Rotter Sopasakis V, Gogg S, Jansson PA, Laakso M, Smith U. Visfatin is an adipokine, but is not regulated by thiazolidinediones.  J Clin Endocrinol Metab. 2006;  91 1181-1184
  • 21 Haider DG, Mittermayer F, Schaller G, Artwohl M, Baumgartner-Parzer SM, Prager G, Roden M, Wolzt M. Free fatty acids normalize a rosiglitazone-induced visfatin release.  Am J Physiol Endocrinol Metab. 2006;  291 E885-E890
  • 22 Goldberg RB, Kendall DM, Deeg MA Buse JB, Zagar AJ, Pinaire JA Tan MH, Khan MA, Perez AT, Jacober SJ, GLAI Study Investigators. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.  Diabetes Care. 2005;  28 1547-1554
  • 23 Pfützner A, Marx N, Walcher D, Löbig M, Seidel DD, Forst T. Impact of rosiglitazone on visfatin and adiponectin plasma concentrations in patients with type 2 diabetes and coronary artery disease.  Clin Lab. , in press
  • 24 Pfützner A, Forst T, Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M. The release of the adipocytokine visfatin is regulated by glucose and insulin (Diabetologia 2006; 49: 1909-1914).  Diabetologia. 2006;  49 2795

Correspondence

A. PfütznerMD,PhD 

Professor of Applied Clinical Research

Institute for Clinical Research and Development

Parcusstrasse 8

55116 Mainz

Germany

Phone: +49/6131/576 36 13

Fax: +49/6131/576 36 11

Email: andreasp@ikfe.de

    >