Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2018; 24(32): 3663-3670
Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3663
C-peptide as a key risk factor for non-alcoholic fatty liver disease in the United States population
Amporn Atsawarungruangkit, Jirat Chenbhanich, George Dickstein
Amporn Atsawarungruangkit, Jirat Chenbhanich, George Dickstein, Department of Medicine, MetroWest Medical Center, Framingham, MA 01702, United States
Amporn Atsawarungruangkit, Jirat Chenbhanich, George Dickstein, Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, United States
Author contributions: Atsawarungruangkit A contributed to the study concept and design, analysis and interpretation of data, and preparation of manuscript; Chenbhanich J and Dickstein G contributed to interpretation of data and preparation and manuscript; all authors read and approved the final manuscript.
Institutional review board statement: This study uses the publicly available data from the Third National Health and Nutrition Examination Survey (NHANES III), which is conducted by the National Center for Health Statistics (NCHS). The NHANES protocol was approved by the NCHS Research Ethics Review Board.
Informed consent statement: In NHANES III, the consent form was signed by participants in the survey.
Conflict-of-interest statement: No conflict of interest exists.
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:
Correspondence to: Amporn Atsawarungruangkit, BPharm, MD, Doctor, Research Fellow, Department of Medicine, MetroWest Medical Center, 115 Lincoln St., Framingham, MA 01702, United States.
Telephone: +1-857-3126114
Received: May 30, 2018
Peer-review started: May 31, 2018
First decision: July 4, 2018
Revised: July 6, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: August 28, 2018

To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease (NAFLD) in United States population.


Using the National Health and Nutrition Examination Survey (NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD (e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05.


Of 18825 participants aged ≥ 20, 3235 participants (n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2, were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase (ALT), total protein, being Mexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level.


Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.

Keywords: Insulin resistance, Fatty liver, Hepatosteatosis, Metabolic syndrome, C-peptide

Core tip: Non-alcoholic fatty liver disease (NAFLD) is a growing global epidemic and associated with many conditions and factors, including insulin resistance. However, C-peptide has not been used in practice to assess insulin resistance in NAFLD patients. Using a large national dataset, we demonstrated that three most important risk factors for NAFLD are waist circumference, fasting C-peptide, and alanine aminotransferase, respectively. Such results revealed that C-peptide superior to measurement of fasting insulin levels and can potentially be used for screening or monitoring the degree of insulin resistance in NAFLD.