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CC BY-NC-ND 4.0 · Horm Metab Res 2020; 52(11): 809-814
DOI: 10.1055/a-1216-4405
Endocrine Care

No Independent Association of Circulating Fetuin-A with Insulin Sensitivity in Young Women

Sabrina Reif
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Sarah Moschko
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Christina Gar
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Uta Ferrari
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
4   Department of Geriatrics, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
,
Nina Hesse
5   Klinik und Poliklinik für Radiologie, Klinikum der Universität München, München, Germany
,
Nora N. Sommer
5   Klinik und Poliklinik für Radiologie, Klinikum der Universität München, München, Germany
,
Jochen Seißler
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Andreas Lechner
1   Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
2   Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany
3   German Center for Diabetes Research (DZD), Neuherberg, Germany
› Author Affiliations Funding Information: German Center for Diabetes Research; Helmholtz Zentrum München; Klinikum der Universität München
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Abstract

Animal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

Key words

type 2 diabetes - metabolic syndrome - non-alcoholic fatty liver disease - mineral metabolism

Supplementary Material



Publication History

Received: 20 January 2020

Accepted after revision: 08 July 2020

Article published online:
06 August 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Holt SG, Smith ER. Fetuin-A-containing calciprotein particles in mineral trafficking and vascular disease. Nephrol Dial Transplant 2016; 31: 1583-1587
    CrossrefPubMedGoogle Scholar
  • 2 Hennige AM, Staiger H, Wicke C. et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PloS one 2008; 3: e1765
    CrossrefPubMedGoogle Scholar
  • 3 Pal D, Dasgupta S, Kundu R. et al. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 2012; 18: 1279-1285
    CrossrefPubMedGoogle Scholar
  • 4 Srinivas PR, Deutsch DD, Mathews ST. et al. Recombinant human alpha 2-HS glycoprotein inhibits insulin-stimulated mitogenic pathway without affecting metabolic signalling in Chinese hamster ovary cells overexpressing the human insulin receptor. Cell Signal 1996; 8: 567-573
    CrossrefPubMedGoogle Scholar
  • 5 Stefan N, Haring HU. Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat Med 2013; 19: 394-395
    CrossrefPubMedGoogle Scholar
  • 6 Stefan N, Hennige AM, Staiger H. et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 2006; 29: 853-857
    CrossrefPubMedGoogle Scholar
  • 7 Erdmann J, Salmhofer H, Knauss A. et al. Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus. Regul Peptides 2012; 178: 6-10
    CrossrefPubMedGoogle Scholar
  • 8 Ishibashi A, Ikeda Y, Ohguro T. et al. Serum fetuin-A is an independent marker of insulin resistance in Japanese men. J Atheroscler Thromb 2010; 17: 925-933
    CrossrefPubMedGoogle Scholar
  • 9 Mori K, Emoto M, Yokoyama H. et al. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 2006; 29: 468
    CrossrefPubMedGoogle Scholar
  • 10 Ou HY, Yang YC, Wu HT. et al. Increased fetuin-A concentrations in impaired glucose tolerance with or without nonalcoholic fatty liver disease, but not impaired fasting glucose. J Clin Endocrinol Metab 2012; 97: 4717-4723
    CrossrefPubMedGoogle Scholar
  • 11 Rottenkolber M, Ferrari U, Holland L. et al. The diabetes risk phenotype of young women with recent gestational diabetes. J Clin Endocrinol Metab 2015; 100: E910-E918
    CrossrefPubMedGoogle Scholar
  • 12 Sujana C, Huth C, Zierer A. et al. Association of fetuin-A with incident type 2 diabetes: results from the MONICA/KORA Augsburg study and a systematic meta-Analysis. Eur J Endocrinol 2018; 178: 389-398
    CrossrefPubMedGoogle Scholar
  • 13 Stefan N, Sun Q, Fritsche A. et al. 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 2014; 9: e92238
    CrossrefPubMedGoogle Scholar
  • 14 Kroger J, Meidtner K, Stefan N. et al. Circulating fetuin-A and risk of type 2 diabetes: A mendelian randomization analysis. Diabetes 2018; 67: 1200-1205
    CrossrefPubMedGoogle Scholar
  • 15 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
    CrossrefPubMedGoogle Scholar