The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Iron Depletion by Phlebotomy Improves Insulin Resistance in Patients With Nonalcoholic Fatty Liver Disease and Hyperferritinemia: Evidence from a Case-Control Study
Abstract
OBJECTIVES: Hyperferritinemia is frequently observed in nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome characterized by hepatic insulin resistance and considered high cardiovascular risk. Iron depletion by phlebotomy has been reported to decrease insulin resistance in NAFLD in small, uncontrolled studies. Aims of this study were to define the relationship between ferritin and iron stores in patients with NAFLD, the effect of iron depletion on insulin resistance, and whether basal ferritin levels influence treatment outcome. METHODS: Subjects were included if ferritin and/or ALT were persistently elevated after 4 months of standard therapy. Sixty-four phlebotomized subjects were matched 1:1 for age, sex, ferritin, obesity, and ALT levels with patients who underwent lifestyle modifications only. Insulin resistance was evaluated by insulin levels, determined by RIA and the HOMA-R index, at baseline and after 8 months. RESULTS: Baseline ferritin levels were associated with body iron stores (P<0.0001). Iron depletion produced a significantly larger decrease in insulin resistance (P=0.0016 for insulin, P=0.0042 for HOMA-R) compared with nutritional counseling alone, independent of changes in BMI, baseline HOMA-R, and the presence of the metabolic syndrome. Iron depletion was more effective in reducing HOMA-R in patients in the top two tertiles of ferritin concentrations (P<0.05 vs controls), and in carriers of the mutations in the HFE gene of hereditary hemochromatosis (P<0.05 vs noncarriers). CONCLUSIONS: Given that phlebotomy reduces insulin resistance, which is associated with liver tissue damage, future studies should evaluate the effect of iron depletion on liver histology and cardiovascular end points.
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Cites
Nonalcoholic Fatty Liver Disease
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Self-citationReactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · cited 1×
“insulin, leading to peripheral hyperinsulinemia (26), and may increase the cellular oxidative stress, inhibiting the internalization and the actions of insulin (27).”
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A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis
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Cross-Talk Between Iron Metabolism and Diabetes
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Prevalence of Body Iron Excess in the Metabolic Syndrome
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Cited by
EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
(2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.004 · Cited by 4,836
Kell, D. B., & Pretorius, E. (2014) · Metallomics · doi:10.1039/c3mt00347g · Cited by 667
Preclinical models of non-alcoholic fatty liver disease
Santhekadur, P. K., Kumar, D. P., & Sanyal, A. J. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.031 · Cited by 380
The role of iron in type 2 diabetes in humans
Rajpathak, S. N., Crandall, J. P., Wylie-Rosett, J., Kabat, G. C., Rohan, T. E., & Hu, F. B. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.04.005 · Cited by 363
Involvement of free radicals and oxidative stress in NAFLD/NASH
Sumida, Y., Niki, E., Naito, Y., & Yoshikawa, T. (2013) · Free Radical Research · doi:10.3109/10715762.2013.837577 · Cited by 280
Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
Dharmalingam, M., & Yamasandhi, P. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_585_17 · Cited by 239
Pathways underlying iron accumulation in human nonalcoholic fatty liver disease
Aigner, E., Theurl, I., Theurl, M., Lederer, D., Haufe, H., Dietze, O., Strasser, M., Datz, C., & Weiss, G. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.5.1374 · Cited by 190
Iron homeostasis in the metabolic syndrome
Datz, C., Felder, T. K., Niederseer, D., & Aigner, E. (2013) · European Journal of Clinical Investigation · doi:10.1111/eci.12032 · Cited by 181
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Review article: the iron overload syndromes
Siddique, A., & Kowdley, K. V. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2012.05051.x · Cited by 162
Hepatocellular carcinoma in nonalcoholic fatty liver: role of environmental and genetic factors
Dongiovanni, P. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i36.12945 · Cited by 145
Self-citationIron Overload Is Associated with Hepatic Oxidative Damage to DNA in Nonalcoholic Steatohepatitis
Fujita, N., Miyachi, H., Tanaka, H., Takeo, M., Nakagawa, N., Kobayashi, Y., Iwasa, M., Watanabe, S., & Takei, Y. (2009) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0725 · Cited by 107
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Metadata
- Authors
- Valenti, L., Fracanzani, A. L., Dongiovanni, P., Bugianesi, E., Marchesini, G., Manzini, P., Vanni, E., & Fargion, S.
- Venue
- The American Journal of Gastroenterology
- Published
- 2007-06
- Volume
- 102
- Issue
- 6
- Pages
- 1251-1258
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W2052131645
- Cited by
- 290
- References
- 8
- FWCI
- 13.82
- Type
- journal article
- Language
- en
- Open access
- closed
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