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

J Endocrinol Invest. 2018 Jan;41(1):33-47. doi: 10.1007/s40618-017-0697-8. Epub 2017 Jun 22.


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.

Keywords: Fetuin-A; Meta-analysis; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Humans
  • Insulin Resistance
  • Risk Factors
  • alpha-2-HS-Glycoprotein / metabolism*


  • Biomarkers
  • alpha-2-HS-Glycoprotein