Skip to main content
Erschienen in: Acta Diabetologica 1/2010

01.03.2010 | Review Article

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

verfasst von: Wenjing Ruan, Maode Lai

Erschienen in: Acta Diabetologica | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607CrossRefPubMed Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607CrossRefPubMed
2.
Zurück zum Zitat Reaven GM (1993) Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 44:121–131CrossRefPubMed Reaven GM (1993) Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 44:121–131CrossRefPubMed
3.
Zurück zum Zitat Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406CrossRefPubMed Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406CrossRefPubMed
4.
Zurück zum Zitat 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 52:1210–1214CrossRefPubMed 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 52:1210–1214CrossRefPubMed
6.
Zurück zum Zitat Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34PubMed Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34PubMed
7.
Zurück zum Zitat 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 95:179–186CrossRefPubMed 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 95:179–186CrossRefPubMed
8.
Zurück zum Zitat 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 271:30322–30325CrossRefPubMed 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 271:30322–30325CrossRefPubMed
9.
Zurück zum Zitat 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 94:12981–12986CrossRefPubMed 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 94:12981–12986CrossRefPubMed
10.
Zurück zum Zitat Yamanaka Y, Wilson EM, Rosenfeld RG, Oh Y (1997) Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem 272:30729–30734CrossRefPubMed Yamanaka Y, Wilson EM, Rosenfeld RG, Oh Y (1997) Inhibition of insulin receptor activation by insulin-like growth factor binding proteins. J Biol Chem 272:30729–30734CrossRefPubMed
11.
Zurück zum Zitat Coverley JA, Baxter RC (1997) Phosphorylation of insulin-like growth factor binding proteins. Mol Cell Endocrinol 128:1–5CrossRefPubMed Coverley JA, Baxter RC (1997) Phosphorylation of insulin-like growth factor binding proteins. Mol Cell Endocrinol 128:1–5CrossRefPubMed
12.
Zurück zum Zitat Maile LA, Holly JM (1999) Insulin-like growth factor binding protein (IGFBP) proteolysis: occurrence, identification, role and regulation. Growth Horm IGF Res 9:85–95CrossRefPubMed Maile LA, Holly JM (1999) Insulin-like growth factor binding protein (IGFBP) proteolysis: occurrence, identification, role and regulation. Growth Horm IGF Res 9:85–95CrossRefPubMed
13.
Zurück zum Zitat 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 78:1119–1127CrossRefPubMed 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 78:1119–1127CrossRefPubMed
14.
Zurück zum Zitat 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 55:2333–2339CrossRefPubMed 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 55:2333–2339CrossRefPubMed
15.
Zurück zum Zitat Baxter RC (2000) Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278:E967–976PubMed Baxter RC (2000) Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278:E967–976PubMed
16.
Zurück zum Zitat Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809PubMed Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809PubMed
17.
Zurück zum Zitat Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ (2001) The biology of white adipocyte proliferation. Obes Rev 2:239–254CrossRefPubMed Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ (2001) The biology of white adipocyte proliferation. Obes Rev 2:239–254CrossRefPubMed
18.
Zurück zum Zitat Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556CrossRefPubMed Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556CrossRefPubMed
19.
Zurück zum Zitat 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 174:289–297CrossRefPubMed 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 174:289–297CrossRefPubMed
20.
Zurück zum Zitat Rajkumar K, Modric T, Murphy LJ (1999) Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice. J Endocrinol 162:457–465CrossRefPubMed Rajkumar K, Modric T, Murphy LJ (1999) Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice. J Endocrinol 162:457–465CrossRefPubMed
21.
Zurück zum Zitat Rajkumar K, Barron D, Lewitt MS, Murphy LJ (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136:4029–4034CrossRefPubMed Rajkumar K, Barron D, Lewitt MS, Murphy LJ (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136:4029–4034CrossRefPubMed
22.
Zurück zum Zitat 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 49:457–465CrossRefPubMed 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 49:457–465CrossRefPubMed
23.
Zurück zum Zitat 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 98:1818–1825CrossRefPubMed 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 98:1818–1825CrossRefPubMed
24.
Zurück zum Zitat Lewitt MS, Denyer GS, Cooney GJ, Baxter RC (1991) Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129:2254–2256CrossRefPubMed Lewitt MS, Denyer GS, Cooney GJ, Baxter RC (1991) Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129:2254–2256CrossRefPubMed
25.
Zurück zum Zitat 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 135:1863–1868CrossRefPubMed 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 135:1863–1868CrossRefPubMed
26.
Zurück zum Zitat 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 56:285–294CrossRefPubMed 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 56:285–294CrossRefPubMed
27.
Zurück zum Zitat 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 275:23462–23470CrossRefPubMed 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 275:23462–23470CrossRefPubMed
28.
Zurück zum Zitat 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 90:6588–6595CrossRefPubMed 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 90:6588–6595CrossRefPubMed
29.
Zurück zum Zitat 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:E937–945PubMed 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:E937–945PubMed
30.
Zurück zum Zitat 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 61:159–164CrossRefPubMed 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 61:159–164CrossRefPubMed
31.
Zurück zum Zitat 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 83:1467–1471CrossRefPubMed 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 83:1467–1471CrossRefPubMed
32.
Zurück zum Zitat 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 269:30835–30841PubMed 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 269:30835–30841PubMed
33.
Zurück zum Zitat 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 80:3227–3232CrossRefPubMed 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 80:3227–3232CrossRefPubMed
34.
Zurück zum Zitat 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 83:4426–4430CrossRefPubMed 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 83:4426–4430CrossRefPubMed
35.
Zurück zum Zitat 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 74:1355–1360CrossRefPubMed 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 74:1355–1360CrossRefPubMed
36.
Zurück zum Zitat 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 90:1483–1488CrossRefPubMed 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 90:1483–1488CrossRefPubMed
37.
Zurück zum Zitat 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 4:1320–1326CrossRefPubMed 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 4:1320–1326CrossRefPubMed
38.
Zurück zum Zitat 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 86:952–961CrossRefPubMed 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 86:952–961CrossRefPubMed
39.
Zurück zum Zitat 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 267:11949–11956PubMed 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 267:11949–11956PubMed
40.
Zurück zum Zitat 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 129:1201–1206CrossRefPubMed 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 129:1201–1206CrossRefPubMed
41.
Zurück zum Zitat 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 83:4355–4362CrossRefPubMed 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 83:4355–4362CrossRefPubMed
42.
Zurück zum Zitat 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 29:1535–1537CrossRefPubMed 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 29:1535–1537CrossRefPubMed
43.
Zurück zum Zitat 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 81:4492–4495CrossRefPubMed 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 81:4492–4495CrossRefPubMed
44.
Zurück zum Zitat 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 172:932–939CrossRefPubMed 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 172:932–939CrossRefPubMed
45.
Zurück zum Zitat Morris DV, Falcone T (1996) The relationship between insulin sensitivity and insulin-like growth factor-binding protein-1. Gynecol Endocrinol 10:407–412CrossRefPubMed Morris DV, Falcone T (1996) The relationship between insulin sensitivity and insulin-like growth factor-binding protein-1. Gynecol Endocrinol 10:407–412CrossRefPubMed
46.
Zurück zum Zitat 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 44:333–339CrossRefPubMed 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 44:333–339CrossRefPubMed
47.
Zurück zum Zitat 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 25:1807–1812CrossRefPubMed 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 25:1807–1812CrossRefPubMed
48.
Zurück zum Zitat 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) 50:221–228CrossRef 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) 50:221–228CrossRef
49.
Zurück zum Zitat 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 83:1935–1939CrossRefPubMed 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 83:1935–1939CrossRefPubMed
50.
Zurück zum Zitat 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 140:231–234CrossRefPubMed 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 140:231–234CrossRefPubMed
51.
Zurück zum Zitat 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) 48:487–492CrossRef 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) 48:487–492CrossRef
52.
Zurück zum Zitat 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 9:43–51CrossRefPubMed 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 9:43–51CrossRefPubMed
53.
Zurück zum Zitat 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 51:2629–2636CrossRefPubMed 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 51:2629–2636CrossRefPubMed
54.
Zurück zum Zitat 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 89:114–120CrossRefPubMed 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 89:114–120CrossRefPubMed
55.
Zurück zum Zitat 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 32:424–428CrossRefPubMed 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 32:424–428CrossRefPubMed
56.
Zurück zum Zitat 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 90:1550–1556CrossRefPubMed 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 90:1550–1556CrossRefPubMed
57.
Zurück zum Zitat 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 81:860–863CrossRefPubMed 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 81:860–863CrossRefPubMed
58.
Zurück zum Zitat 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 30:2343–2348CrossRefPubMed 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 30:2343–2348CrossRefPubMed
59.
Zurück zum Zitat 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 114:371–376CrossRefPubMed 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 114:371–376CrossRefPubMed
60.
Zurück zum Zitat 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 91:3287–3295CrossRefPubMed 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 91:3287–3295CrossRefPubMed
61.
Zurück zum Zitat 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 106:939–944CrossRefPubMed 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 106:939–944CrossRefPubMed
62.
Zurück zum Zitat 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 25:617–621CrossRefPubMed 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 25:617–621CrossRefPubMed
63.
Zurück zum Zitat 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 11:141–148CrossRefPubMed 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 11:141–148CrossRefPubMed
64.
Zurück zum Zitat Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470CrossRefPubMed Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470CrossRefPubMed
65.
Zurück zum Zitat 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 88:1019–1023CrossRefPubMed 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 88:1019–1023CrossRefPubMed
66.
Zurück zum Zitat 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 28:412–419CrossRefPubMed 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 28:412–419CrossRefPubMed
67.
Zurück zum Zitat 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 85:2402–2410CrossRefPubMed 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 85:2402–2410CrossRefPubMed
68.
Zurück zum Zitat 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 85:4491–4499CrossRefPubMed 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 85:4491–4499CrossRefPubMed
69.
Zurück zum Zitat Duncan GE, Li SM, Zhou XH (2004) Prevalence and trends of a metabolic syndrome phenotype among U.S. adolescents, 1999–2000. Diabetes Care 27:2438–2443CrossRefPubMed Duncan GE, Li SM, Zhou XH (2004) Prevalence and trends of a metabolic syndrome phenotype among U.S. adolescents, 1999–2000. Diabetes Care 27:2438–2443CrossRefPubMed
70.
Zurück zum Zitat Reaven PD, Traustadottir T, Brennan J, Nader PR (2005) Cardiovascular risk factors associated with insulin resistance in children persist into late adolescence. Diabetes Care 28:148–150CrossRefPubMed Reaven PD, Traustadottir T, Brennan J, Nader PR (2005) Cardiovascular risk factors associated with insulin resistance in children persist into late adolescence. Diabetes Care 28:148–150CrossRefPubMed
71.
Zurück zum Zitat 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 29:1599–1604CrossRefPubMed 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 29:1599–1604CrossRefPubMed
72.
Zurück zum Zitat 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 89:108–113CrossRefPubMed 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 89:108–113CrossRefPubMed
73.
Zurück zum Zitat Steinberger J (2003) Diagnosis of the metabolic syndrome in children. Curr Opin Lipidol 14:555–559CrossRefPubMed Steinberger J (2003) Diagnosis of the metabolic syndrome in children. Curr Opin Lipidol 14:555–559CrossRefPubMed
74.
Zurück zum Zitat Le Stunff C, Bougneres P (1994) Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes 43:696–702CrossRefPubMed Le Stunff C, Bougneres P (1994) Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes 43:696–702CrossRefPubMed
75.
Zurück zum Zitat 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 110:1251–1257CrossRefPubMed 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 110:1251–1257CrossRefPubMed
76.
Zurück zum Zitat 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 288:2709–2716CrossRefPubMed 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 288:2709–2716CrossRefPubMed
77.
Zurück zum Zitat 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 110:1245–1250CrossRefPubMed 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 110:1245–1250CrossRefPubMed
78.
Zurück zum Zitat 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 28:385–390CrossRefPubMed 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 28:385–390CrossRefPubMed
79.
Zurück zum Zitat 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 112:3066–3072CrossRefPubMed 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 112:3066–3072CrossRefPubMed
80.
Zurück zum Zitat 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 15:314–322CrossRefPubMed 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 15:314–322CrossRefPubMed
81.
Zurück zum Zitat 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 74:1432–1435CrossRefPubMed 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 74:1432–1435CrossRefPubMed
82.
Zurück zum Zitat 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 21:355–359CrossRefPubMed 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 21:355–359CrossRefPubMed
83.
Zurück zum Zitat Caprio S, Amiel SA, Merkel P, Tamborlane WV (1993) Insulin-resistant syndromes in children. Horm Res 39 Suppl 3:112–114CrossRefPubMed Caprio S, Amiel SA, Merkel P, Tamborlane WV (1993) Insulin-resistant syndromes in children. Horm Res 39 Suppl 3:112–114CrossRefPubMed
84.
Zurück zum Zitat 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 80:927–932CrossRefPubMed 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 80:927–932CrossRefPubMed
85.
Zurück zum Zitat 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 22:28–32PubMed 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 22:28–32PubMed
86.
Zurück zum Zitat 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 212:83–90CrossRefPubMed 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 212:83–90CrossRefPubMed
87.
Zurück zum Zitat 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 6:354–359PubMedCrossRef 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 6:354–359PubMedCrossRef
88.
Zurück zum Zitat 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 346:393–403CrossRefPubMed 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 346:393–403CrossRefPubMed
Metadaten
Titel
Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?
verfasst von
Wenjing Ruan
Maode Lai
Publikationsdatum
01.03.2010
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 1/2010
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-009-0142-3

Weitere Artikel der Ausgabe 1/2010

Acta Diabetologica 1/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.