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Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?

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Abstract

Insulin-like growth factor (IGF) binding proteins (IGFBPs) moved on to contain both IGF high- and low-affinity binders, exerting mitogenic and metabolic actions through its complex interplay between IGF/insulin and its IGF/insulin-independent manner. Progress on the metabolic-related function of IGFBPs has been rapid in recent years. A wealth of studies in 3T3-L1 adipocytes and the transgenic mice models demonstrated that IGFBPs played important roles in the pathogenesis of obesity and insulin resistance. Studies conducted in humans demonstrated the close relation between IGFBPs and the components of the metabolic syndrome. Abnormal expression of IGFBP was detected in various states of the metabolic disorders, suggesting that it could be used as a convenient and sensitive marker of insulin resistance, identification of insulin-resistant individuals at high cardiovascular risk, and may be an earlier marker of the metabolic syndrome. These exciting findings bring us new insight into the elucidation of the metabolic syndrome, which may have important clinical implications.

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References

  1. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607

    Article  CAS  PubMed  Google Scholar 

  2. Reaven GM (1993) Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 44:121–131

    Article  CAS  PubMed  Google Scholar 

  3. Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406

    Article  CAS  PubMed  Google Scholar 

  4. Alexander CM, Landsman PB, Teutsch SM, Haffner SM (2003) NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52:1210–1214

    Article  CAS  PubMed  Google Scholar 

  5. Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231

    Article  CAS  PubMed  Google Scholar 

  6. Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34

    CAS  PubMed  Google Scholar 

  7. Zapf J, Hauri C, Futo E, Hussain M, Rutishauser J, Maack CA, Froesch ER (1995) Intravenously injected insulin-like growth factor (IGF) I/IGF binding protein-3 complex exerts insulin-like effects in hypophysectomized, but not in normal rats. J Clin Invest 95:179–186

    Article  CAS  PubMed  Google Scholar 

  8. Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG (1996) Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem 271:30322–30325

    Article  CAS  PubMed  Google Scholar 

  9. Kim HS, Nagalla SR, Oh Y, Wilson E, Roberts CT Jr, Rosenfeld RG (1997) Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc Natl Acad Sci USA 94:12981–12986

    Article  CAS  PubMed  Google Scholar 

  10. Yamanaka Y, Wilson EM, Rosenfeld RG, Oh Y (1997) Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem 272:30729–30734

    Article  CAS  PubMed  Google Scholar 

  11. Coverley JA, Baxter RC (1997) Phosphorylation of insulin-like growth factor binding proteins. Mol Cell Endocrinol 128:1–5

    Article  CAS  PubMed  Google Scholar 

  12. Maile LA, Holly JM (1999) Insulin-like growth factor binding protein (IGFBP) proteolysis: occurrence, identification, role and regulation. Growth Horm IGF Res 9:85–95

    Article  CAS  PubMed  Google Scholar 

  13. Bang P, Brismar K, Rosenfeld RG (1994) Increased proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3) in noninsulin-dependent diabetes mellitus serum, with elevation of a 29-kilodalton (kDa) glycosylated IGFBP-3 fragment contained in the approximately 130- to 150-kDa ternary complex. J Clin Endocrinol Metab 78:1119–1127

    Article  CAS  PubMed  Google Scholar 

  14. Lopez-Bermejo A, Khosravi J, Fernandez-Real JM, Hwa V, Pratt KL, Casamitjana R, Garcia-Gil MM, Rosenfeld RG, Ricart W (2006) Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25). Diabetes 55:2333–2339

    Article  CAS  PubMed  Google Scholar 

  15. Baxter RC (2000) Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278:E967–976

    CAS  PubMed  Google Scholar 

  16. Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809

    CAS  PubMed  Google Scholar 

  17. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ (2001) The biology of white adipocyte proliferation. Obes Rev 2:239–254

    Article  CAS  PubMed  Google Scholar 

  18. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  CAS  PubMed  Google Scholar 

  19. Siddals KW, Westwood M, Gibson JM, White A (2002) IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte. J Endocrinol 174:289–297

    Article  CAS  PubMed  Google Scholar 

  20. Rajkumar K, Modric T, Murphy LJ (1999) Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice. J Endocrinol 162:457–465

    Article  CAS  PubMed  Google Scholar 

  21. Rajkumar K, Barron D, Lewitt MS, Murphy LJ (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136:4029–4034

    Article  CAS  PubMed  Google Scholar 

  22. Crossey PA, Jones JS, Miell JP (2000) Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance. Diabetes 49:457–465

    Article  CAS  PubMed  Google Scholar 

  23. Rajkumar K, Krsek M, Dheen ST, Murphy LJ (1996) Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice. J Clin Invest 98:1818–1825

    Article  CAS  PubMed  Google Scholar 

  24. Lewitt MS, Denyer GS, Cooney GJ, Baxter RC (1991) Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129:2254–2256

    Article  CAS  PubMed  Google Scholar 

  25. Boney CM, Moats-Staats BM, Stiles AD, D’Ercole AJ (1994) Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins during adipogenesis. Endocrinology 135:1863–1868

    Article  CAS  PubMed  Google Scholar 

  26. Wheatcroft SB, Kearney MT, Shah AM, Ezzat VA, Miell JR, Modo M, Williams SC, Cawthorn WP, Medina-Gomez G, Vidal-Puig A, Sethi JK, Crossey PA (2007) IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes 56:285–294

    Article  CAS  PubMed  Google Scholar 

  27. Schedlich LJ, Le Page SL, Firth SM, Briggs LJ, Jans DA, Baxter RC (2000) Nuclear import of insulin-like growth factor-binding protein-3 and -5 is mediated by the importin beta subunit. J Biol Chem 275:23462–23470

    Article  CAS  PubMed  Google Scholar 

  28. Chan SS, Twigg SM, Firth SM, Baxter RC (2005) Insulin-like growth factor binding protein-3 leads to insulin resistance in adipocytes. J Clin Endocrinol Metab 90:6588–6595

    Article  CAS  PubMed  Google Scholar 

  29. Silha JV, Gui Y, Murphy LJ (2002) Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice. Am J Physiol Endocrinol Metab 283:E937–945

    CAS  PubMed  Google Scholar 

  30. Kim HS, Ali O, Shim M, Lee KW, Vuguin P, Muzumdar R, Barzilai N, Cohen P (2007) Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo. Pediatr Res 61:159–164

    Article  CAS  PubMed  Google Scholar 

  31. Attia N, Tamborlane WV, Heptulla R, Maggs D, Grozman A, Sherwin RS, Caprio S (1998) The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity. J Clin Endocrinol Metab 83:1467–1471

    Article  CAS  PubMed  Google Scholar 

  32. Suwanichkul A, Allander SV, Morris SL, Powell DR (1994) Glucocorticoids and insulin regulate expression of the human gene for insulin-like growth factor-binding protein-1 through proximal promoter elements. J Biol Chem 269:30835–30841

    CAS  PubMed  Google Scholar 

  33. Yki-Jarvinen H, Makimattila S, Utriainen T, Rutanen EM (1995) Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo. J Clin Endocrinol Metab 80:3227–3232

    Article  CAS  PubMed  Google Scholar 

  34. Katz LE, Satin-Smith MS, Collett-Solberg P, Baker L, Stanley CA, Cohen P (1998) Dual regulation of insulin-like growth factor binding protein-1 levels by insulin and cortisol during fasting. J Clin Endocrinol Metab 83:4426–4430

    Article  CAS  PubMed  Google Scholar 

  35. Conover CA, Lee PD, Kanaley JA, Clarkson JT, Jensen MD (1992) Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab 74:1355–1360

    Article  CAS  PubMed  Google Scholar 

  36. Liew CF, Wise SD, Yeo KP, Lee KO (2005) Insulin-like growth factor binding protein-1 is independently affected by ethnicity, insulin sensitivity, and leptin in healthy, glucose-tolerant young men. J Clin Endocrinol Metab 90:1483–1488

    Article  CAS  PubMed  Google Scholar 

  37. Boni-Schnetzler M, Schmid C, Mary JL, Zimmerli B, Meier PJ, Zapf J, Schwander J, Froesch ER (1990) Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes. Mol Endocrinol 4:1320–1326

    Article  CAS  PubMed  Google Scholar 

  38. Zapf J, Schmid C, Guler HP, Waldvogel M, Hauri C, Futo E, Hossenlopp P, Binoux M, Froesch ER (1990) Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia. J Clin Invest 86:952–961

    Article  CAS  PubMed  Google Scholar 

  39. Camacho-Hubner C, Busby WH Jr, McCusker RH, Wright G, Clemmons DR (1992) Identification of the forms of insulin-like growth factor-binding proteins produced by human fibroblasts and the mechanisms that regulate their secretion. J Biol Chem 267:11949–11956

    CAS  PubMed  Google Scholar 

  40. Camacho-Hubner C, Clemmons DR, D’Ercole AJ (1991) Regulation of insulin-like growth factor (IGF) binding proteins in transgenic mice with altered expression of growth hormone and IGF-I. Endocrinology 129:1201–1206

    Article  CAS  PubMed  Google Scholar 

  41. Hwa V, Tomasini-Sprenger C, Bermejo AL, Rosenfeld RG, Plymate SR (1998) Characterization of insulin-like growth factor-binding protein-related protein-1 in prostate cells. J Clin Endocrinol Metab 83:4355–4362

    Article  CAS  PubMed  Google Scholar 

  42. Maddux BA, Chan A, De Filippis EA, Mandarino LJ, Goldfine ID (2006) IGF-binding protein-1 levels are related to insulin-mediated glucose disposal and are a potential serum marker of insulin resistance. Diabetes Care 29:1535–1537

    Article  CAS  PubMed  Google Scholar 

  43. Mogul HR, Marshall M, Frey M, Burke HB, Wynn PS, Wilker S, Southern AL, Gambert SR (1996) Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women. J Clin Endocrinol Metab 81:4492–4495

    Article  CAS  PubMed  Google Scholar 

  44. Buyalos RP, Pekonen F, Halme JK, Judd HL, Rutanen EM (1995) The relationship between circulating androgens, obesity, and hyperinsulinemia on serum insulin-like growth factor binding protein-1 in the polycystic ovarian syndrome. Am J Obstet Gynecol 172:932–939

    Article  CAS  PubMed  Google Scholar 

  45. Morris DV, Falcone T (1996) The relationship between insulin sensitivity and insulin-like growth factor-binding protein-1. Gynecol Endocrinol 10:407–412

    Article  CAS  PubMed  Google Scholar 

  46. Heald AH, Cruickshank JK, Riste LK, Cade JE, Anderson S, Greenhalgh A, Sampayo J, Taylor W, Fraser W, White A, Gibson JM (2001) Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations. Diabetologia 44:333–339

    Article  CAS  PubMed  Google Scholar 

  47. Leinonen ES, Salonen JT, Salonen RM, Koistinen RA, Leinonen PJ, Sarna SS, Taskinen MR (2002) Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes. Diabetes Care 25:1807–1812

    Article  CAS  PubMed  Google Scholar 

  48. Mohamed-Ali V, Pinkney JH, Panahloo A, Cwyfan-Hughes S, Holly JM, Yudkin JS (1999) Insulin-like growth factor binding protein-1 in NIDDM: relationship with the insulin resistance syndrome. Clin Endocrinol (Oxf) 50:221–228

    Article  CAS  Google Scholar 

  49. Travers SH, Labarta JI, Gargosky SE, Rosenfeld RG, Jeffers BW, Eckel RH (1998) Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children. J Clin Endocrinol Metab 83:1935–1939

    Article  CAS  PubMed  Google Scholar 

  50. Saitoh H, Kamoda T, Nakahara S, Hirano T, Matsui A (1999) Insulin-like growth factor binding protein-1 as a predictor of glucose-stimulated hyperinsulinemia in prepubertal obese children. Eur J Endocrinol 140:231–234

    Article  CAS  PubMed  Google Scholar 

  51. Saitoh H, Kamoda T, Nakahara S, Hirano T, Nakamura N (1998) Serum concentrations of insulin, insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-1 and -3 and growth hormone binding protein in obese children: fasting IGFBP-1 is suppressed in normoinsulinaemic obese children. Clin Endocrinol (Oxf) 48:487–492

    Article  CAS  Google Scholar 

  52. Motaghedi R, Gujral S, Sinha S, Sison C, Ten S, Maclaren NK (2007) Insulin-like growth factor binding protein-1 to screen for insulin resistance in children. Diabetes Technol Ther 9:43–51

    Article  CAS  PubMed  Google Scholar 

  53. Heald AH, Siddals KW, Fraser W, Taylor W, Kaushal K, Morris J, Young RJ, White A, Gibson JM (2002) Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes. Diabetes 51:2629–2636

    Article  CAS  PubMed  Google Scholar 

  54. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D (2004) The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab 89:114–120

    Article  CAS  PubMed  Google Scholar 

  55. Harrela M, Koistinen R, Tuomilehto J, Nissinen A, Seppala M (2000) Low serum insulin-like growth factor-binding protein-1 is associated with an unfavourable cardiovascular risk profile in elderly men. Ann Med 32:424–428

    Article  CAS  PubMed  Google Scholar 

  56. Kalme T, Seppala M, Qiao Q, Koistinen R, Nissinen A, Harrela M, Loukovaara M, Leinonen P, Tuomilehto J (2005) Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men. J Clin Endocrinol Metab 90:1550–1556

    Article  CAS  PubMed  Google Scholar 

  57. Gibson JM, Westwood M, Young RJ, White A (1996) Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). J Clin Endocrinol Metab 81:860–863

    Article  CAS  PubMed  Google Scholar 

  58. Wallander M, Norhammar A, Malmberg K, Ohrvik J, Ryden L, Brismar K (2007) IGF binding protein 1 predicts cardiovascular morbidity and mortality in patients with acute myocardial infarction and type 2 diabetes. Diabetes Care 30:2343–2348

    Article  CAS  PubMed  Google Scholar 

  59. Heald AH, Kaushal K, Siddals KW, Rudenski AS, Anderson SG, Gibson JM (2006) Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome. Exp Clin Endocrinol Diabetes 114:371–376

    Article  CAS  PubMed  Google Scholar 

  60. Martin RM, Holly JM, Davey Smith G, Gunnell D (2006) Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort. J Clin Endocrinol Metab 91:3287–3295

    Article  CAS  PubMed  Google Scholar 

  61. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T (2002) Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case–control study. Circulation 106:939–944

    Article  CAS  PubMed  Google Scholar 

  62. Kawachi S, Takeda N, Sasaki A, Kokubo Y, Takami K, Sarui H, Hayashi M, Yamakita N, Yasuda K (2005) Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 are associated with early carotid atherosclerosis. Arterioscler Thromb Vasc Biol 25:617–621

    Article  CAS  PubMed  Google Scholar 

  63. Shao L, Huang Q, Luo M, Lai M (2004) Detection of the differentially expressed gene IGF-binding protein-related protein-1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients. Endocr Relat Cancer 11:141–148

    Article  CAS  PubMed  Google Scholar 

  64. Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470

    Article  CAS  PubMed  Google Scholar 

  65. Soonthornpun S, Setasuban W, Thamprasit A, Chayanunnukul W, Rattarasarn C, Geater A (2003) Novel insulin sensitivity index derived from oral glucose tolerance test. J Clin Endocrinol Metab 88:1019–1023

    Article  CAS  PubMed  Google Scholar 

  66. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  67. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410

    Article  CAS  PubMed  Google Scholar 

  68. Song SH, McIntyre SS, Shah H, Veldhuis JD, Hayes PC, Butler PC (2000) Direct measurement of pulsatile insulin secretion from the portal vein in human subjects. J Clin Endocrinol Metab 85:4491–4499

    Article  CAS  PubMed  Google Scholar 

  69. Duncan GE, Li SM, Zhou XH (2004) Prevalence and trends of a metabolic syndrome phenotype among U.S. adolescents, 1999–2000. Diabetes Care 27:2438–2443

    Article  PubMed  Google Scholar 

  70. Reaven PD, Traustadottir T, Brennan J, Nader PR (2005) Cardiovascular risk factors associated with insulin resistance in children persist into late adolescence. Diabetes Care 28:148–150

    Article  PubMed  Google Scholar 

  71. Bacha F, Saad R, Gungor N, Arslanian SA (2006) Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents? Diabetes Care 29:1599–1604

    Article  PubMed  Google Scholar 

  72. Cruz ML, Weigensberg MJ, Huang TT, Ball G, Shaibi GQ, Goran MI (2004) The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab 89:108–113

    Article  CAS  PubMed  Google Scholar 

  73. Steinberger J (2003) Diagnosis of the metabolic syndrome in children. Curr Opin Lipidol 14:555–559

    Article  CAS  PubMed  Google Scholar 

  74. Le Stunff C, Bougneres P (1994) Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes 43:696–702

    Article  PubMed  Google Scholar 

  75. Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP (2004) National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 110:1251–1257

    Article  PubMed  Google Scholar 

  76. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716

    Article  PubMed  Google Scholar 

  77. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR (2004) Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110:1245–1250

    Article  PubMed  Google Scholar 

  78. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Ballantyne CM, Heiss G (2005) The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 28:385–390

    Article  PubMed  Google Scholar 

  79. Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB (2005) Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112:3066–3072

    Article  CAS  PubMed  Google Scholar 

  80. Frystyk J, Skjaerbaek C, Vestbo E, Fisker S, Orskov H (1999) Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes. Diabetes Metab Res Rev 15:314–322

    Article  CAS  PubMed  Google Scholar 

  81. Slowinska-Srzednicka J, Zgliczynski W, Makowska A, Jeske W, Brzezinska A, Soszynski P, Zgliczynski S (1992) An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome due to coexistent obesity. J Clin Endocrinol Metab 74:1432–1435

    Article  CAS  PubMed  Google Scholar 

  82. Nam SY, Lee EJ, Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB (1997) Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord 21:355–359

    Article  CAS  PubMed  Google Scholar 

  83. Caprio S, Amiel SA, Merkel P, Tamborlane WV (1993) Insulin-resistant syndromes in children. Horm Res 39 Suppl 3:112–114

    Article  CAS  PubMed  Google Scholar 

  84. Grinspoon S, Clemmons D, Swearingen B, Klibanski A (1995) Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly. J Clin Endocrinol Metab 80:927–932

    Article  CAS  PubMed  Google Scholar 

  85. Alford FP, Hew FL, Christopher MC, Rantzau C (1999) Insulin sensitivity in growth hormone (GH)-deficient adults and effect of GH replacement therapy. J Endocrinol Invest 22:28–32

    CAS  PubMed  Google Scholar 

  86. Lin J, Lai M, Huang Q, Ma Y, Cui J, Ruan W (2007) Methylation patterns of IGFBP7 in colon cancer cell lines are associated with levels of gene expression. J Pathol 212:83–90

    Article  CAS  PubMed  Google Scholar 

  87. Ruan W, Xu E, Xu F, Ma Y, Deng H, Huang Q, Lv B, Hu H, Lin J, Cui J, Di M, Dong J, Lai M (2007) IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. Cancer Biol Ther 6:354–359

    Article  CAS  PubMed  Google Scholar 

  88. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from China National ‘‘973’’ program (2007CB914304), The National Scientific Foundation of China (30770989), and Zhejiang Provincial Natural Science Foundation of China (D2080011).

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Correspondence to Maode Lai.

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Ruan, W., Lai, M. Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?. Acta Diabetol 47, 5–14 (2010). https://doi.org/10.1007/s00592-009-0142-3

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