Skip to main content

Advertisement

SpringerLink
Log in

The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background and objective

Fetuin-A is a liver-derived circulating protein that is associated with insulin resistance and diabetes. The objective of this systematic review and meta-analysis of published observational studies was to investigate mean levels of fetuin-A in T2D patients and the relationship between blood fetuin-A levels and T2D risk.

Materials and methods

PubMed, Embase, Google Scholar, Web of Science, and The Cochrane Library were systematically searched for potential relevant studies up to 1 December 2016. Natural logarithm-transformed estimate risks, standard mean differences on the basis of Hedges’s adjusted g, and 95% confidence intervals (CIs) were calculated for all eligible studies and were combined to measure the pooled data using random-effects model.

Results

A total of 32 studies including 27 case–control and 5 cohort studies were included in the current study. Fetuin-A levels in T2D patients were significantly higher than control groups [Hedges’ g = 1.73, 95% CI (1.25–2.22), P < 0.001], with significant heterogeneity across studies (P < 0.001, I 2 = 98.46%). Findings from meta-analyses of cohort studies showed a statistically significant association between fetuin-A levels and T2D risk [rate ratio = 1.62, 95% CI (1.26–2.08), P < 0.001], with no significant heterogeneity (P = 0.10, I 2 = 46.06%).

Conclusion

We found a significant relationship between the fetuin-A levels with T2D risk. Although fetuin-A may be as a potential screening and prediction biomarker or a therapeutic target in T2D patients, further studies are required in this regard.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Association AD (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Supplement 1):S62–S69

    Article  Google Scholar 

  2. Beulens JW, Grobbee DE, Nealb B (2010) The global burden of diabetes and its complications: an emerging pandemic. Eur J Cardiovasc Prev Rehabil 17(1 suppl):s3–s8

    PubMed  Google Scholar 

  3. Iroz A, Couty J-P, Postic C (2015) Hepatokines: unlocking the multi-organ network in metabolic diseases. Diabetologia 58(8):1699–1703

    Article  CAS  PubMed  Google Scholar 

  4. Stefan N, Häring H-U (2013) The role of hepatokines in metabolism. Nat Rev Endocrinol 9(3):144–152

    Article  CAS  PubMed  Google Scholar 

  5. Denecke B, Gräber S, Schäfer C, Heiss A, Wöltje M, Jahnen-Dechent W (2003) Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J 376(1):135–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chatterjee P, Seal S, Mukherjee S, Kundu R, Mukherjee S, Ray S, Mukhopadhyay S, Majumdar SS, Bhattacharya S (2013) Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. J Biol Chem 288(39):28324–28330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS, Jen K-LC, Charron MJ, Jahnen-Dechent W, Grunberger G (2002) Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 51(8):2450–2458

    Article  CAS  PubMed  Google Scholar 

  8. Mathews ST, Rakhade S, Zhou X, Parker GC, Coscina DV, Grunberger G (2006) Fetuin-null mice are protected against obesity and insulin resistance associated with aging. Biochem Biophys Res Commun 350(2):437–443

    Article  CAS  PubMed  Google Scholar 

  9. Sun Q, Cornelis MC, Manson JE, Hu FB (2013) Plasma levels of fetuin-A and hepatic enzymes and risk of type 2 diabetes in women in the US. Diabetes 62(1):49–55

    Article  CAS  PubMed  Google Scholar 

  10. Stefan N, Sun Q, Fritsche A, Machann J, Schick F, Gerst F, Jeppesen C, Joost H-G, Hu FB, Boeing H (2014) Impact of the adipokine adiponectin and the hepatokine fetuin-A on the development of type 2 diabetes: prospective cohort-and cross-sectional phenotyping studies. PLoS One 9(3):e92238

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Häring H-U, Stefan N (2008) Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One 3(3):e1765

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dasgupta S, Bhattacharya S, Biswas A, Majumdar SS, Mukhopadhyay S, Ray S, Bhattacharya S (2010) NF-κB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem J 429(3):451–462

    Article  CAS  PubMed  Google Scholar 

  13. Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS, Grunberger G (2000) α 2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164(1):87–98

    Article  CAS  PubMed  Google Scholar 

  14. Scialla JJ, Kao WL, Crainiceanu C, Sozio SM, Oberai PC, Shafi T, Coresh J, Powe NR, Plantinga LC, Jaar BG (2014) Biomarkers of vascular calcification and mortality in patients with ESRD. Clin J Am Soc Nephrol 9(4):745–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y (2006) Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29(2):468

    Article  PubMed  Google Scholar 

  16. Kim HR, Kim S-H, Han M-J, Yoon Y-S, Oh D-J (2013) The ratio of osteoprotegerin to fetuin-a is independently associated with vascular stiffness in hemodialysis patients. Nephron Clin Pract 123(3–4):165–172

    Article  CAS  PubMed  Google Scholar 

  17. Gunduz FO, Yildirmak ST, Temizel M, Faki Y, Cakmak M, Durmuscan M, Sezgin F (2011) Serum visfatin and fetuin-a levels and glycemic control in patients with obese type 2 diabetes mellitus. Diabetes Metab J 35(5):523–528

    Article  PubMed  PubMed Central  Google Scholar 

  18. Axelsson J, Wang X, Ketteler M, Qureshi AR, Heimbürger O, Bárány P, Lindholm B, Nordfors L, Stenvinkel P (2008) Is fetuin-A/α2-Heremans-Schmid glycoprotein associated with the metabolic syndrome in patients with chronic kidney disease? Am J Nephrol 28(4):669–676

    Article  CAS  PubMed  Google Scholar 

  19. Ford ML, Tomlinson LA, Smith ER, Rajkumar C, Holt SG (2010) Fetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stages 3 and 4. Nephrol Dial Transplant 25:1853–1858

    Article  CAS  PubMed  Google Scholar 

  20. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 283(15):2008–2012

    Article  CAS  PubMed  Google Scholar 

  21. Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, Tugwell P (2000) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 3rd Symposium on Systematic Reviews. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed Feb 2017

  22. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5(1):1

    Article  Google Scholar 

  23. Tönjes A, Fasshauer M, Kratzsch J, Stumvoll M, Blüher M (2010) Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One 5(11):e13911

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ishibashi A, Ikeda Y, Ohguro T, Kumon Y, Yamanaka S, Takata H, Inoue M, Suehiro T, Terada Y (2010) Serum fetuin-A is an independent marker of insulin resistance in Japanese men. J Atheroscler Thromb 17(9):925–933

    Article  CAS  PubMed  Google Scholar 

  25. Song A, Xu M, Bi Y, Xu Y, Huang Y, Li M, Wang T, Wu Y, Liu Y, Li X (2011) Serum fetuin-A associates with type 2 diabetes and insulin resistance in Chinese adults. PLoS One 6(4):e19228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lorant DP, Grujicic M, Hoebaus C, Brix J-M, Hoellerl F, Schernthaner G, Koppensteiner R, Schernthaner G-H (2011) Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes Care 34(1):156–161

    Article  CAS  PubMed  Google Scholar 

  27. Krajnc M, Pečovnik-Balon B, Hojs R, Rupreht M (2011) Comparison of coronary artery calcification and some coronary artery calcification risk factors in patients on haemodialysis and in patients with type 2 diabetes. J Int Med Res 39(3):1006–1015

    Article  CAS  PubMed  Google Scholar 

  28. Ou HY, Yang YC, Wu HT, Wu JS, Lu FH, Chang CJ (2011) Serum fetuin-A concentrations are elevated in subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes. Clin Endocrinol 75(4):450–455

    Article  CAS  Google Scholar 

  29. Erdmann J, Salmhofer H, Knauß A, Mayr M, Wagenpfeil S, Sypchenko O, Luppa P, Schusdziarra V (2012) Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus. Regul Pept 178(1):6–10

    Article  CAS  PubMed  Google Scholar 

  30. Zhao Z-W, Lin C-G, Wu L-Z, Luo Y-K, Fan L, X-f Dong, Zheng H (2013) Serum fetuin-A levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes. Biomarkers 18(2):160–164

    Article  CAS  PubMed  Google Scholar 

  31. Faizehalkuobaili KH (2013) Elevated fetuin-A level associated with an atherogenic lipid profile in type 2 diabetes. Int J Pharm Sci Rev Res 21(1):266–269

    Google Scholar 

  32. Fatima F, Zuberi NA, Noor S, Alam SM, Alam F (2013) Role of fetuin-A in insulin resistance in type 2 diabetes mellitus. Annals of Abbasi Shaheed Hospital & Karachi Medical & Dental College 18(2):58–62

  33. Obuchi A, Adachi H, Enomoto M, Fukami A, Kumagai E, Nakamura S, Yoshimura A, Nohara Y, Nakao E, Umeki Y, Fukumoto Y, Imaizumi T (2014) High plasma fetuin-A levels are associated with metabolic syndrome among males but not females in a Japanese general population. Diabetes Res Clin Pract 106(1):128–135

    Article  CAS  PubMed  Google Scholar 

  34. Dutta D, Mondal SA, Kumar M, Hasanoor Reza AH, Biswas D, Singh P, Chakrabarti S, Mukhopadhyay S (2014) Serum fetuin-A concentration predicts glycaemic outcomes in people with prediabetes: a prospective study from eastern India. Diabet Med 31(12):1594–1599

    Article  CAS  PubMed  Google Scholar 

  35. Ahmed LI, Mousa SG, Mohamed NAE-G, Yousry ZA, Abd-El Khalaa MR (2014) Fetuin-A and type II diabetes mellitus. Egypt J Intern Med 26(4):157

    Article  Google Scholar 

  36. Zhao C, Hou J, Wang S, Jiang R (2015) Relation of serum and vitreous concentrations of fetuin-A with diabetic retinopathy. Med Sci Monit 21:1839

    Article  PubMed  PubMed Central  Google Scholar 

  37. Yin L, Cai W-J, Zhu L-Y, Li J, Su X-H, Wang X-L, Chang X-Y, Sun K (2015) Association of plasma fetuin-A and clinical characteristics in patients with new-onset type 2 diabetes mellitus. Int J Clin Exp Med 8(1):991

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Akin F, Celik O, Altun I, Ayca B, Diker VO, Satilmis S, Sahin C (2015) Relationship of fibroblast growth factor 23 and fetuin-A to coronary atherosclerosis. J Diabetes Complicat 29(4):550–555

    Article  PubMed  Google Scholar 

  39. Zhou ZW, Ju HX, Sun MZ, Fu QP, Chen HM, Ji HB, Ji F, Jiang DM (2016) Serum fetuin-A levels are independently correlated with vascular endothelial growth factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy. Clin Chim Acta 455:113–117

    Article  CAS  PubMed  Google Scholar 

  40. Reinehr T, Karges B, Meissner T, Wiegand S, Stoffel-Wagner B, Holl RW, Woelfle J (2016) Inflammatory markers in obese adolescents with type 2 diabetes and their relationship to hepatokines and adipokines. J Pediatr 173:131–135

    Article  CAS  PubMed  Google Scholar 

  41. Ali SA, Nassif WM, Abdelaziz DH (2016) Alterations in serum levels of fetuin A and selenoprotein P in chronic hepatitis C patients with concomitant type 2 diabetes: a case-control study. Clin Res Hepatol Gastroenterol 40(4):465–470

    Article  CAS  PubMed  Google Scholar 

  42. Sindhu S, Akhter N, Shenouda S, Wilson A, Ahmad R (2016) Plasma fetuin-A/α2-HS-glycoprotein correlates negatively with inflammatory cytokines, chemokines and activation biomarkers in individuals with type-2 diabetes. BMC Immunol 17(1):33

    Article  PubMed  PubMed Central  Google Scholar 

  43. Eleftheriadou I, Grigoropoulou P, Kokkinos A, Mourouzis I, Perrea D, Katsilambros N, Sfikakis PP, Tentolouris N (2017) Association of plasma fetuin-A levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus. J Diabetes Complicat 31(3):599–604

    Article  PubMed  Google Scholar 

  44. Beigi T, Shafaei A, Khoshnia M, Marjani A (2015) Serum fetuin a level, liver enzymes activities and insulin resistance in patients with type 2 diabetes. J Med Sci (Faisalabad) 15(5):229–234

    Article  Google Scholar 

  45. Ix JH, Wassel CL, Kanaya AM, Vittinghoff E, Johnson KC, Koster A, Cauley JA, Harris TB, Cummings SR, Shlipak MG (2008) Fetuin-A and incident diabetes mellitus in older persons. JAMA 300(2):182–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ix JH, Biggs ML, Mukamal KJ, Kizer JR, Zieman SJ, Siscovick DS, Mozaffarian D, Jensen MK, Nelson L, Ruderman N (2012) Association of fetuin-A with incident diabetes mellitus in community-living older adults the cardiovascular health study. Circulation 125(19):2316–2322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Aroner SA, Mukamal KJ, St-Jules DE, Budoff MJ, Katz R, Criqui MH, Allison MA, de Boer IH, Siscovick DS, Ix JH (2017) Fetuin-A and risk of diabetes independent of liver fat content the multi-ethnic study of atherosclerosis. Am J Epidemiol 185(1):54–64

    Article  PubMed  Google Scholar 

  48. Roever L, Resende E, Borges A (2015) The role of hepatokines in cardiovascular disease. J Metab Syndr 5(1):1–3

    Google Scholar 

  49. Jung TW, Yoo HJ, Choi KM (2016) Implication of hepatokines in metabolic disorders and cardiovascular diseases. BBA Clin 5:108–113

    Article  PubMed  PubMed Central  Google Scholar 

  50. Yoo HJ, Choi KM (2015) Hepatokines as a link between obesity and cardiovascular diseases. Diabetes Metab J 39(1):10–15

    Article  PubMed  PubMed Central  Google Scholar 

  51. Robinson KN, Teran-Garcia M (2016) From infancy to aging: biological and behavioral modifiers of fetuin-A. Biochimie 124:141–149

    Article  CAS  PubMed  Google Scholar 

  52. Mukhopadhyay S, Mondal S, Kumar M, Dutta D (2014) Proinflammatory and antiinflammatory attributes of fetuin-A: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome. Endocr Pract 20(12):1345–1351

    PubMed  Google Scholar 

  53. Stefan N, Fritsche A, Weikert C, Boeing H, Joost H-G, Häring H-U, Schulze MB (2008) Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 57(10):2762–2767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Laughlin GA, Barrett-Connor E, Cummins KM, Daniels LB, Wassel CL, Ix JH (2013) Sex-specific association of fetuin-A with type 2 diabetes in older community-dwelling adults the rancho Bernardo study. Diabetes Care 36(7):1994–2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kadoglou NP, Kottas G, Lampropoulos S, Vitta I, Liapis CD (2014) Serum levels of fetuin-A, osteoprotegerin and osteopontin in patients with coronary artery disease: effects of statin (HMGCoA-reductase inhibitor) therapy. Clin Drug Investig 34(3):165–171

    Article  CAS  PubMed  Google Scholar 

  56. Ochi A, Mori K, Emoto M, Nakatani S, Morioka T, Motoyama K, Fukumoto S, Imanishi Y, Koyama H, Ishimura E (2014) Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression. PLoS One 9(2):e88704

    Article  PubMed  PubMed Central  Google Scholar 

  57. Haukeland JW, Dahl TB, Yndestad A, Gladhaug IP, Løberg EM, Haaland T, Konopski Z, Wium C, Aasheim ET, Johansen OE (2012) Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol 166(3):503–510

    Article  CAS  PubMed  Google Scholar 

  58. Jenkins NT, McKenzie JA, Hagberg JM, Witkowski S (2011) Plasma fetuin-A concentrations in young and older high-and low-active men. Metabolism 60(2):265–271

    Article  CAS  PubMed  Google Scholar 

  59. Inoue M, Takata H, Ikeda Y, Suehiro T, Inada S, Osaki F, Arii K, Kumon Y, Hashimoto K (2008) A promoter polymorphism of the α2-HS glycoprotein gene is associated with its transcriptional activity. Diabetes Res Clin Pract 79(1):164–170

    Article  CAS  PubMed  Google Scholar 

  60. Metry G, Stenvinkel P, Qureshi A, Carrero J, Yilmaz M, Bárány P, Snaedal S, Heimbürger O, Lindholm B, Suliman M (2008) Low serum fetuin-A concentration predicts poor outcome only in the presence of inflammation in prevalent haemodialysis patients. Eur J Clin Invest 38(11):804–811

    Article  CAS  PubMed  Google Scholar 

  61. Munafò MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet 20(9):439–444

    Article  PubMed  Google Scholar 

  62. Roca-Rivada A, Alonso J, Al-Massadi O, Castelao C, Peinado JR, Seoane LM, Casanueva FF, Pardo M (2011) Secretome analysis of rat adipose tissues shows location-specific roles for each depot type. J Proteomics 74(7):1068–1079

    Article  CAS  PubMed  Google Scholar 

  63. Pérez-Sotelo D, Roca-Rivada A, Larrosa-García M, Castelao C, Baamonde I, Baltar J, Crujeiras AB, Seoane LM, Casanueva FF, Pardo M (2017) Visceral and subcutaneous adipose tissue express and secrete functional alpha2hsglycoprotein (fetuin A) especially in obesity. Endocrine 55(2):435–446

    Article  PubMed  Google Scholar 

  64. Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA (2006) Association between human fetuin-A and the metabolic syndrome data from the heart and soul study. Circulation 113(14):1760–1767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Brix JM, Stingl H, Höllerl F, Schernthaner GH, Kopp H-P, Schernthaner G (2010) Elevated Fetuin-A concentrations in morbid obesity decrease after dramatic weight loss. J Clin Endocrinol Metab 95(11):4877–4881

    Article  CAS  PubMed  Google Scholar 

  66. Trepanowski J, Mey J, Varady KA (2015) Fetuin-A: a novel link between obesity and related complications. Int J Obes 39(5):734–741

    Article  CAS  Google Scholar 

  67. Murdolo G, Tortoioli C, Celi F, Bini V, Papi F, Brozzetti A, Falorni A (2017) Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren. Endocrine 56(2):357–365

    Article  CAS  PubMed  Google Scholar 

  68. Abate N, Chandalia M (2003) The impact of ethnicity on type 2 diabetes. J Diabetes Complicat 17(1):39–58

    Article  PubMed  Google Scholar 

  69. Sun Z-L, Xie Q-Y, Guo G-L, Ma K, Huang Y-Y (2014) Serum fetuin-A levels in patients with cardiovascular disease: a meta-analysis. BioMed Res Int 2014:1–9

    Google Scholar 

  70. Liu H, Choi JW, Yun JW (2012) Gender differences in rat plasma proteome in response to high-fat diet. Proteomics 12(2):269–283

    Article  CAS  PubMed  Google Scholar 

  71. Kautzky-Willer A, Harreiter J, Pacini G (2016) Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocr Rev 37(3):278–316

    Article  PubMed  PubMed Central  Google Scholar 

  72. Eraso LH, Ginwala N, Qasim AN, Mehta NN, Dlugash R, Kapoor S, Schwartz S, Schutta M, Iqbal N, Mohler ER (2010) Association of lower plasma fetuin-A levels with peripheral arterial disease in type 2 diabetes. Diabetes Care 33(2):408–410

    Article  CAS  PubMed  Google Scholar 

  73. Roos M, Oikonomou D, von Eynatten M, Luppa PB, Heemann U, Lutz J, Baumann M, Nawroth PP, Bierhaus A, Humpert PM (2010) Associations of fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy. Cardiovasc Diabetol 9(1):1

    Article  Google Scholar 

  74. Smith ER, Ford ML, Tomlinson LA, Rocks BF, Rajkumar C, Holt SG (2010) Poor agreement between commercial ELISAs for plasma fetuin-A: an effect of protein glycosylation? Clin Chim Acta 411(17):1367–1370

    Article  CAS  PubMed  Google Scholar 

  75. Martin B, Warram J, Krolewski A, Soeldner J, Kahn C, Bergman R (1992) Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 340(8825):925–929

    Article  CAS  PubMed  Google Scholar 

  76. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Kröber SM, Machicao F, Fritsche A, Häring H-U (2006) α2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 29(4):853–857

    Article  CAS  PubMed  Google Scholar 

  77. Auberger P, Falquerho L, Contreres JO, Pages G, Le Cam G, Rossi B, Le Cam A (1989) Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell 58(4):631–640

    Article  CAS  PubMed  Google Scholar 

  78. Malin SK, Mulya A, Fealy CE, Haus JM, Pagadala MR, Scelsi AR, Huang H, Flask CA, McCullough AJ, Kirwan JP (2013) Fetuin-A is linked to improved glucose tolerance after short-term exercise training in nonalcoholic fatty liver disease. J Appl Physiol 115(7):988–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S (2012) Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18(8):1279–1285

    Article  CAS  PubMed  Google Scholar 

  80. Vionnet N, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Leprêtre F, Lecoeur C, Gallina P (2000) Genomewide search for type 2 diabetes–susceptibility genes in French Whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2–diabetes locus on chromosome 1q21–q24. Am J Hum Genet 67(6):1470–1480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ix JH, Sharma K (2010) Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol 21(3):406–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jung TW, Youn B-S, Choi HY, Lee SY, Hong HC, Yang SJ, Yoo HJ, Kim B-H, Baik SH, Choi KM (2013) Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. Biochem Pharmacol 86(7):960–969

    Article  CAS  PubMed  Google Scholar 

  83. Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, Federspil G, Sechi LA, Vettor R (2005) Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 152(1):113–118

    Article  CAS  PubMed  Google Scholar 

  84. Musso G, Gambino R, Durazzo M, Biroli G, Carello M, Faga E, Pacini G, De Michieli F, Rabbione L, Premoli A (2005) Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology 42(5):1175–1183

    Article  CAS  PubMed  Google Scholar 

  85. Fisher E, Stefan N, Saar K, Drogan D, Schulze MB, Fritsche A, Joost H-G, Häring H-U, Hubner N, Boeing H (2009) Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam study. Circ Cardiovasc Genet 2(6):607–613

    Article  CAS  PubMed  Google Scholar 

  86. Dahlman I, Eriksson P, Kaaman M, Jiao H, Lindgren C, Kere J, Arner P (2004) α2-Heremans–Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action. Diabetologia 47(11):1974–1979

    Article  CAS  PubMed  Google Scholar 

  87. Siddiq A, Lepretre F, Hercberg S, Froguel P, Gibson F (2005) A synonymous coding polymorphism in the α2-Heremans-Schmid glycoprotein gene is associated with type 2 diabetes in French Caucasians. Diabetes 54(8):2477–2481

    Article  CAS  PubMed  Google Scholar 

  88. Osawa M, Umetsu K, Ohki T, Nagasawa T, Suzuki T, Takeichi S (1996) Molecular evidence for human alpha2-HS glycoprotein (AHSG) polymorphism. Hum Genet 99(1):18–21

    Article  Google Scholar 

  89. Mori K, Emoto M, Inaba M (2011) Fetuin-A: a multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov 5(2):124–146

    Article  CAS  PubMed  Google Scholar 

  90. Wang H, Sama AE (2012) Anti-inflammatory role of fetuin-A in injury and infection. Curr Mol Med 12(5):625–633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran

    F. Roshanzamir

  2. Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    F. Roshanzamir, M. H. Rouhani, R. Ghiasvand & S. M. Safavi

  3. Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

    F. Roshanzamir & S. M. Safavi

  4. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    M. Miraghajani

  5. Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

    M. H. Rouhani & R. Ghiasvand

  6. Department of Biostatistics and Epidemiology, Health School, Isfahan University of Medical Sciences, Isfahan, Iran

    M. Mansourian

Authors
  1. F. Roshanzamir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Miraghajani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. H. Rouhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Mansourian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Ghiasvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. M. Safavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. M. Safavi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical disclosure

All included studies have been reviewed by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Informed consent

All persons gave their informed consent prior to their inclusion in the studies.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roshanzamir, F., Miraghajani, M., Rouhani, M.H. et al. The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies. J Endocrinol Invest 41, 33–47 (2018). https://doi.org/10.1007/s40618-017-0697-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0697-8

Keywords

Search

Navigation