Serum ferritin is associated with non-alcoholic fatty liver disease and decreased Β-cell function in non-diabetic men and women
Kristina M Utzschneider, Anna Largajolli, Alessandra Bertoldo, Santica Marcovina, James E Nelson, Matthew M Yeh, Kris V Kowdley, Steven E Kahn, Kristina M Utzschneider, Anna Largajolli, Alessandra Bertoldo, Santica Marcovina, James E Nelson, Matthew M Yeh, Kris V Kowdley, Steven E Kahn
Abstract
Aims: We sought to determine whether NAFLD is associated with poorer β-cell function and if any β-cell dysfunction is associated with abnormal markers of iron or inflammation.
Methods: This was a cross-sectional study of 15 non-diabetic adults with NAFLD and 15 non-diabetic age and BMI-matched controls. Insulin sensitivity was measured by isotope-labeled hyperinsulinemic-euglycemic clamps and β-cell function by both oral (OGTT) and intravenous glucose tolerance tests. Liver and abdominal fat composition was evaluated by CT scan. Fasting serum levels of ferritin, transferrin-iron saturation, IL-6, TNFα and hsCRP were measured.
Results: Compared to controls, subjects with NAFLD had lower hepatic and systemic insulin sensitivity and β-cell function was decreased as measured by the oral disposition index. Fasting serum ferritin and transferrin-iron saturation were higher in NAFLD and were positively associated with liver fat. Serum ferritin was negatively associated with β-cell function measured by both oral and intravenous tests, but was not associated with insulin sensitivity. IL-6, TNFα and hsCRP did not differ between groups and did not correlate with serum ferritin, liver fat or measures of β-cell function.
Conclusions: These findings support a potential pathophysiological link between iron metabolism, liver fat and diabetes risk.
Keywords: Fatty liver; Ferritin; Insulin secretion in vivo; Insulin sensitivity.
Conflict of interest statement
Disclosures: The authors have nothing to disclose. There is no conflict of interest.
Published by Elsevier Inc.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3943487/bin/nihms544840f1.jpg)
Figure 2
Glucose (A), insulin (B), free…
Figure 2
Glucose (A), insulin (B), free fatty acid levels (C) and whole body insulin…
Figure 3
Correlations between iron and liver…
Figure 3
Correlations between iron and liver fat measured by the liver/spleen ratio (A and…
- Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans.Kratz M, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Callahan HS, Song X, Di C, Utzschneider KM. Kratz M, et al. Am J Clin Nutr. 2014 Jun;99(6):1385-96. doi: 10.3945/ajcn.113.075457. Epub 2014 Apr 16. Am J Clin Nutr. 2014. PMID: 24740208 Free PMC article. Clinical Trial.
- Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity.Mörwald K, Aigner E, Bergsten P, Brunner SM, Forslund A, Kullberg J, Ahlström H, Manell H, Roomp K, Schütz S, Zsoldos F, Renner W, Furthner D, Maruszczak K, Zandanell S, Weghuber D, Mangge H. Mörwald K, et al. Front Endocrinol (Lausanne). 2020 Jun 18;11:340. doi: 10.3389/fendo.2020.00340. eCollection 2020. Front Endocrinol (Lausanne). 2020. PMID: 32625166 Free PMC article.
- Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease: a cross-sectional study.Yan H, Chang X, Xia M, Bian H, Zhang L, Lin H, Chen G, Zeng M, Gao X. Yan H, et al. Lipids Health Dis. 2013 Oct 27;12:157. doi: 10.1186/1476-511X-12-157. Lipids Health Dis. 2013. PMID: 24160775 Free PMC article.
- Hepatic Insulin Extraction in NAFLD Is Related to Insulin Resistance Rather Than Liver Fat Content.Utzschneider KM, Kahn SE, Polidori DC. Utzschneider KM, et al. J Clin Endocrinol Metab. 2019 May 1;104(5):1855-1865. doi: 10.1210/jc.2018-01808. J Clin Endocrinol Metab. 2019. PMID: 30566676 Free PMC article.
- Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease.Valenti L, Dongiovanni P, Fargion S. Valenti L, et al. World J Gastroenterol. 2012 Aug 7;18(29):3782-6. doi: 10.3748/wjg.v18.i29.3782. World J Gastroenterol. 2012. PMID: 22876027 Free PMC article. Review.
- Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.Maruszczak K, Radzikowski K, Schütz S, Mangge H, Bergsten P, Forslund A, Manell H, Pixner T, Ahlström H, Kullberg J, Mörwald K, Weghuber D. Maruszczak K, et al. Front Endocrinol (Lausanne). 2022 Sep 5;13:1004128. doi: 10.3389/fendo.2022.1004128. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36133310 Free PMC article.
- Oxidative Stress and Lipid Peroxidation: Prospective Associations Between Ferroptosis and Delayed Wound Healing in Diabetic Ulcers.Feng J, Wang J, Wang Y, Huang X, Shao T, Deng X, Cao Y, Zhou M, Zhao C. Feng J, et al. Front Cell Dev Biol. 2022 Jul 8;10:898657. doi: 10.3389/fcell.2022.898657. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35874833 Free PMC article. Review.
- The association between non-alcoholic fatty liver disease and serum ferritin levels in American adults.Yang N, Lu Y, Cao L, Lu M. Yang N, et al. J Clin Lab Anal. 2022 Feb;36(2):e24225. doi: 10.1002/jcla.24225. Epub 2022 Jan 7. J Clin Lab Anal. 2022. PMID: 34997649 Free PMC article.
- Genetic Support of A Causal Relationship Between Iron Status and Type 2 Diabetes: A Mendelian Randomization Study.Wang X, Fang X, Zheng W, Zhou J, Song Z, Xu M, Min J, Wang F. Wang X, et al. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4641-e4651. doi: 10.1210/clinem/dgab454. J Clin Endocrinol Metab. 2021. PMID: 34147035 Free PMC article.
- Association between central obesity indices and iron status indicators among Qatari adults.Kerkadi A, Mohsen Ali R, A H Shehada A, Abdelnasser AbouHassanein E, Moawad J, Bawadi H, Shi Z. Kerkadi A, et al. PLoS One. 2021 Apr 29;16(4):e0250759. doi: 10.1371/journal.pone.0250759. eCollection 2021. PLoS One. 2021. PMID: 33914792 Free PMC article.
- Research Support, N.I.H., Extramural
- Adult
- Case-Control Studies
- Cross-Sectional Studies
- Fatty Liver / blood*
- Fatty Liver / metabolism
- Fatty Liver / physiopathology*
- Female
- Ferritins / blood*
- Glucose Clamp Technique
- Humans
- Insulin Resistance
- Insulin-Secreting Cells / physiology*
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease
- Ferritins
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3943487/bin/nihms544840f2.jpg)
Figure 3
Correlations between iron and liver…
Figure 3
Correlations between iron and liver fat measured by the liver/spleen ratio (A and…
- Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans.Kratz M, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Callahan HS, Song X, Di C, Utzschneider KM. Kratz M, et al. Am J Clin Nutr. 2014 Jun;99(6):1385-96. doi: 10.3945/ajcn.113.075457. Epub 2014 Apr 16. Am J Clin Nutr. 2014. PMID: 24740208 Free PMC article. Clinical Trial.
- Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity.Mörwald K, Aigner E, Bergsten P, Brunner SM, Forslund A, Kullberg J, Ahlström H, Manell H, Roomp K, Schütz S, Zsoldos F, Renner W, Furthner D, Maruszczak K, Zandanell S, Weghuber D, Mangge H. Mörwald K, et al. Front Endocrinol (Lausanne). 2020 Jun 18;11:340. doi: 10.3389/fendo.2020.00340. eCollection 2020. Front Endocrinol (Lausanne). 2020. PMID: 32625166 Free PMC article.
- Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease: a cross-sectional study.Yan H, Chang X, Xia M, Bian H, Zhang L, Lin H, Chen G, Zeng M, Gao X. Yan H, et al. Lipids Health Dis. 2013 Oct 27;12:157. doi: 10.1186/1476-511X-12-157. Lipids Health Dis. 2013. PMID: 24160775 Free PMC article.
- Hepatic Insulin Extraction in NAFLD Is Related to Insulin Resistance Rather Than Liver Fat Content.Utzschneider KM, Kahn SE, Polidori DC. Utzschneider KM, et al. J Clin Endocrinol Metab. 2019 May 1;104(5):1855-1865. doi: 10.1210/jc.2018-01808. J Clin Endocrinol Metab. 2019. PMID: 30566676 Free PMC article.
- Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease.Valenti L, Dongiovanni P, Fargion S. Valenti L, et al. World J Gastroenterol. 2012 Aug 7;18(29):3782-6. doi: 10.3748/wjg.v18.i29.3782. World J Gastroenterol. 2012. PMID: 22876027 Free PMC article. Review.
- Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.Maruszczak K, Radzikowski K, Schütz S, Mangge H, Bergsten P, Forslund A, Manell H, Pixner T, Ahlström H, Kullberg J, Mörwald K, Weghuber D. Maruszczak K, et al. Front Endocrinol (Lausanne). 2022 Sep 5;13:1004128. doi: 10.3389/fendo.2022.1004128. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36133310 Free PMC article.
- Oxidative Stress and Lipid Peroxidation: Prospective Associations Between Ferroptosis and Delayed Wound Healing in Diabetic Ulcers.Feng J, Wang J, Wang Y, Huang X, Shao T, Deng X, Cao Y, Zhou M, Zhao C. Feng J, et al. Front Cell Dev Biol. 2022 Jul 8;10:898657. doi: 10.3389/fcell.2022.898657. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35874833 Free PMC article. Review.
- The association between non-alcoholic fatty liver disease and serum ferritin levels in American adults.Yang N, Lu Y, Cao L, Lu M. Yang N, et al. J Clin Lab Anal. 2022 Feb;36(2):e24225. doi: 10.1002/jcla.24225. Epub 2022 Jan 7. J Clin Lab Anal. 2022. PMID: 34997649 Free PMC article.
- Genetic Support of A Causal Relationship Between Iron Status and Type 2 Diabetes: A Mendelian Randomization Study.Wang X, Fang X, Zheng W, Zhou J, Song Z, Xu M, Min J, Wang F. Wang X, et al. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4641-e4651. doi: 10.1210/clinem/dgab454. J Clin Endocrinol Metab. 2021. PMID: 34147035 Free PMC article.
- Association between central obesity indices and iron status indicators among Qatari adults.Kerkadi A, Mohsen Ali R, A H Shehada A, Abdelnasser AbouHassanein E, Moawad J, Bawadi H, Shi Z. Kerkadi A, et al. PLoS One. 2021 Apr 29;16(4):e0250759. doi: 10.1371/journal.pone.0250759. eCollection 2021. PLoS One. 2021. PMID: 33914792 Free PMC article.
- Research Support, N.I.H., Extramural
- Adult
- Case-Control Studies
- Cross-Sectional Studies
- Fatty Liver / blood*
- Fatty Liver / metabolism
- Fatty Liver / physiopathology*
- Female
- Ferritins / blood*
- Glucose Clamp Technique
- Humans
- Insulin Resistance
- Insulin-Secreting Cells / physiology*
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease
- Ferritins
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3943487/bin/nihms544840f3.jpg)
Source: PubMed