Download PDF
Horm Metab Res 2016; 48(02): 130-136
DOI: 10.1055/s-0035-1559768
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women

A. S. E. Koegelenberg
1   Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
,
R. Schutte
1   Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
2   MRC Research Unit for Hypertension and Cardiovascular disease, North-West University, Potchefstroom, South Africa
,
W. Smith
1   Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
,
A. E. Schutte
1   Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
2   MRC Research Unit for Hypertension and Cardiovascular disease, North-West University, Potchefstroom, South Africa
› Author Affiliations
Further Information

Publication History

received 19 February 2015

accepted 30 July 2015

Publication Date:
08 September 2015 (online)

Also available at
    Permissions and Reprints

Abstract

Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p<0.001). In multivariate-adjusted analyses, IGF-1/IGFBP-3 was inversely associated with the number of metabolic syndrome components in both sexes (men: β=− 0.11; p=0.013 and women: β=− 0.17; p=0.003). Upon inclusion of ROS, γ-GT and CRP, significance was lost. In patients without diabetes, the results for men changed marginally, but were consistent for women. We found an inverse association between bioavailable IGF-1 and the number of metabolic syndrome components. But the relationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1.

Key words

metabolic syndrome - insulin-like growth factor binding protein-3 - inflammation - oxidative stress - γ-glutamyltransferase

Supporting Information

    for this article is available online at for this article is available online at http://www.thieme-connect.de/products
  • Supporting Information
 

  • References

  • 1 Schini-Kerth V. Dual effects of insulin-like growth factor-I on the constitutive and inducible nitric oxide (NO) synthase-dependent formation of NO in vascular cells. J Endocrinol Invest 1999; 22: 82-88
    PubMedSearch in Google Scholar
  • 2 Conti E, Andreotti F, Sestito A, Riccardi P, Menini E, Crea F, Maseri A, Lanza GA. Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol 2002; 89: 973-975
    CrossrefPubMedSearch in Google Scholar
  • 3 Dimmeler S, Zeiher AM. Exercise and Cardiovascular Health Get Active to “AKTivate” Your Endothelial Nitric Oxide Synthase. Circulation 2003; 107: 3118-3120
    CrossrefPubMedSearch in Google Scholar
  • 4 Twickler MT, Cramer MM, Koppeschaar HP. Unraveling Reaven’s syndrome X: serum insulin-like growth factor-I and cardiovascular disease. Circulation 2003; 107: e190-e192
    PubMedSearch in Google Scholar
  • 5 Spies M, Nesic O, Barrow R, Perez-Polo J, Herndon D. Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound. Gene Ther 2001; 8: 1409-1415
    CrossrefPubMedSearch in Google Scholar
  • 6 Conti E, Musumeci M, De Giusti M, Dito E, Mastromarino V, Volpe M. IGF-1 and atherothrombosis: relevance to pathophysiology and therapy. Clin Sci 2011; 120: 377-402
    CrossrefPubMedSearch in Google Scholar
  • 7 Vasan RS, Sullivan LM, D’Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, Wilson PW. Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study. Ann Intern Med 2003; 139: 642-648
    CrossrefPubMedSearch in Google Scholar
  • 8 Sesti G, Sciacqua A, Cardellini M, Marini MA, Maio R, Vatrano M, Succurro E, Lauro R, Federici M, Perticone F. Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care 2005; 28: 120-125
    CrossrefPubMedSearch in Google Scholar
  • 9 Colao A, Di Somma C, Cascella T, Pivonello R, Vitale G, Grasso LF, Lombardi G, Savastano S. Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects. Eur J Endocrinol 2008; 159: 389-397
    CrossrefPubMedSearch in Google Scholar
  • 10 Hu Y, Pete G, Walsh MF, Sowers J, Dunbar JC. Central IGF-1 decreases systemic blood pressure and increases blood flow in selective vascular beds. Horm Metab Res 1996; 28: 211-214
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Alberti K, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart J, James WPT, Loria CM, Smith SC. Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
    CrossrefPubMedSearch in Google Scholar
  • 12 Parekh N, Roberts CB, Vadiveloo M, Puvananayagam T, Albu JB, Lu-Yao GL. Lifestyle, anthropometric, and obesity-related physiologic determinants of insulin-like growth factor-1 in the Third National Health and Nutrition Examination Survey (1988–1994). Ann Epidemiol 2010; 20: 182-193
    CrossrefPubMedSearch in Google Scholar
  • 13 Sierra-Johnson J, Romero-Corral A, Somers V, Lopez-Jimenez F, Malarstig A, Brismar K, Hamsten A, Fisher R, Hellenius M. IGF-I/IGFBP-3 ratio: a mechanistic insight into the metabolic syndrome. Clin Sci 2009; 116: 507-512
    CrossrefPubMedSearch in Google Scholar
  • 14 De Benedetti F, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest 1997; 99: 643-650
    CrossrefPubMedSearch in Google Scholar
  • 15 Efstratiadis G, Tsiaousis G, Athyros VG, Karagianni D, Pavlitou-Tsiontsi A, Giannakou-Darda A, Manes C. Total serum insulin-like growth factor-1 and C-reactive protein in metabolic syndrome with or without diabetes. Angiology 2006; 57: 303-311
    CrossrefPubMedSearch in Google Scholar
  • 16 Scheidegger KJ, James RW, Delafontaine P. Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. J Biol Chem 2000; 275: 26864-26869
    PubMedSearch in Google Scholar
  • 17 Schutte AE, Huisman HW, van Rooyen JM, Malan L, Malan NT, Fourie CMT, Louw R, van der Westhuizen FH, Schutte R. A significant decline in IGF-I may predispose young Africans to subsequent cardiometabolic vulnerability. J Clin Endocrinol Metab 2010; 95: 2503-2507
    CrossrefPubMedSearch in Google Scholar
  • 18 Hamer M, Malan L, Schutte A, Huisman H, Van Rooyen J, Schutte R, Fourie C, Malan N, Seedat Y. Conventional and behavioral risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: The SABPA study. Atherosclerosis 2011; 215: 237-242
    CrossrefPubMedSearch in Google Scholar
  • 19 Norton K, Olds T. Anthropometrica: a textbook of body measurement for sports and health courses. University of New South Wales Press; 1996
    Search in Google Scholar
  • 20 Verrij E, Van Montfrans G, Bos J. Reintroduction of Riva-Rocci measurements to determine systolic blood pressure. Neth J Med 2008; 66: 480-482
    PubMedSearch in Google Scholar
  • 21 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37: 81-90
    CrossrefPubMedSearch in Google Scholar
  • 22 Hayashi I, Morishita Y, Imai K, Nakamura M, Nakachi K, Hayashi T. High-throughput spectrophotometric assay of reactive oxygen species in serum. Mutat Res 2007; 631: 55-61
    CrossrefPubMedSearch in Google Scholar
  • 23 Higashi Y, Peng T, Du J, Sukhanov S, Li Y, Itabe H, Parthasarathy S, Delafontaine P. A redox-sensitive pathway mediates oxidized LDL-induced downregulation of insulin-like growth factor-1 receptor. J Lipid Res 2005; 46: 1266-1277
    CrossrefPubMedSearch in Google Scholar
  • 24 Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y, Taura N, Shibata H, Fujimoto M, Toriyama K. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatology International 2007; 1: 287-294
    CrossrefPubMedSearch in Google Scholar
  • 25 Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 2003; 27: 277-284
    PubMedSearch in Google Scholar
  • 26 Møller S, Juul A, Becker U, Henriksen JH. The acid-labile subunit of the ternary insulin-like growth factor complex in cirrhosis: relation to liver dysfunction. J Hepatol 2000; 32: 441-446
    CrossrefPubMedSearch in Google Scholar
  • 27 Bassanello M, De Palo EF, Lancerin F, Vitale A, Gatti R, Montin U, Ciarleglio FA, Senzolo M, Burra P, Brolese A. Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: A preliminary prospective study. Liver transplantation 2004; 10: 692-698
    CrossrefPubMedSearch in Google Scholar
  • 28 Succurro E, Andreozzi F, Sciacqua A, Hribal ML, Perticone F, Sesti G. Reciprocal association of plasma IGF-1 and interleukin-6 levels with cardiometabolic risk factors in nondiabetic subjects. Diabetes Care 2008; 31: 1886-1888
    CrossrefPubMedSearch in Google Scholar
  • 29 Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation 2004; 109: II2-10
    CrossrefPubMedSearch in Google Scholar
  • 30 Singh U, Devaraj S, Vasquez-Vivar J, Jialal I. C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol 2007; 43: 780-791
    CrossrefPubMedSearch in Google Scholar
  • 31 Kim C, Park H, Kawada T, Kim J, Lim D, Hubbard N, Kwon B, Erickson K, Yu R. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes 2006; 30: 1347-1355
    CrossrefPubMedSearch in Google Scholar
  • 32 Yubero-Serrano EM, Delgado-Lista J, Peña-Orihuela P, Perez-Martinez P, Fuentes F, Marin C, Tunez I, Tinahones FJ, Perez-Jimenez F, Roche HM. Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study. Exp Mol Med 2013; 45: e28
    CrossrefPubMedSearch in Google Scholar
  • 33 Grundy SM. Gamma-glutamyl transferase: another biomarker for metabolic syndrome and cardiovascular risk. Arterioscler Thromb Vasc Biol 2007; 27: 4-7
    CrossrefPubMedSearch in Google Scholar