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Association of insulin resistance with serum ferritin and aminotransferases-iron hypothesis
Jean Huang, Rudruidee Karnchanasorn, Horng-Yih Ou, Wei Feng, Lee-Ming Chuang, Ken C Chiu, Raynald Samoa
Jean Huang, Wei Feng, Ken C Chiu, Raynald Samoa, Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
Jean Huang, Wei Feng, Ken C Chiu, Raynald Samoa, Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502, United States
Rudruidee Karnchanasorn, Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
Horng-Yih Ou, Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
Lee-Ming Chuang, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Lee-Ming Chuang, Graduate Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei 100, Taiwan
Author contributions: Chuang LM, Chiu KC and Samoa R conceived and designed the study; Huang J, Karnchanasorn R and Ou HY obtained data under the direction of Chiu KC, Chuang LM and Samoa R; Feng W, Chiu KC and Samoa R reviewed data; Huang J, Karnchanasorn R, Chuang LM, Chiu KC and Samoa R did statistical analyses and interpreted data; Huang J, Chiu KC and Samoa R drafted the manuscript; all authors revised the manuscript for important intellectual content; Feng W, Chiu KC and Samoa R provided administrative, technical, and material support; Chiu KC and Samoa R contributed equally as senior authors of this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Institutional review board statement: The National Center for Health Statistics of the Centers for Disease Control and Prevention conducted the NHANES III in the United States from 1988 through 1994. This survey was designed to assess the health and nutrition status of a large representative sample in the United States. The survey and data collection was approved by the NHANES Institutional Review Board (IRB).
Informed consent statement: Documented consent was obtained from participants of the NHANES III at the participation of survey.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ken C Chiu, MD, FACE, Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, United States.
kchiu@coh.org
Telephone: +1-626-2180111 Fax: +1-626-2188489
Received: May 10, 2015
Peer-review started: May 12, 2015
First decision: July 27, 2015
Revised: October 19, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: November 20, 2015
Processing time: 197 Days and 7.3 Hours
AIM: To investigate the relationship of iron indices with diabetes mellitus (DM) in those without hemochromatosis.
METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey (NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included (n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated.
RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects (P = 0.0001 to < 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement (P = 0.03 to < 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity (P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration (P = 0.02 to < 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance.
CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2 diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2 diabetes through its effect on liver function.
Core tip: Hemochromatosis and excess iron load has been implicated to play a role in the pathogenesis of diabetes mellitus. Serum ferritin concentration was significantly higher in diabetic subjects. Serum ferritin concentration was negatively associated with insulin sensitivity, but not with beta cell function. The association of alanine aminotransferase correlated with serum ferritin concentration, but not insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance. Disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2 diabetes mellitus through its effect on liver function.
