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
Research background

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Additionally, NAFLD can progress to more severe liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Many factors were found to be independently associated with NAFLD and/or severity of liver fibrosis in NAFLD. Nevertheless, there is limited evidence of the association between NAFLD and C-peptide.

Research motivation

Among many risk factors that are associated with NAFLD, obesity and insulin resistance are probably the most well-known ones. C-peptide levels can be used to measure insulin secretion and a surrogate marker of insulin resistance. However, C-peptide is not routinely used in clinical practice to diagnose type 2 diabetes or monitor insulin resistance status in NAFLD.

Research objectives

The objective of this study was to determine if fasting C-peptide is independently associated with NAFLD using multivariate analysis in the United States general population.

Research methods

Using the National Health and Nutrition Examination Survey 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. The participants with excessive alcohol intake (> 2 drinks per day for males and > 1 drink per day for female) were excluded from the study. 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 selected as predictors in regression model. Univariate logistic regression and multivariate step-wise logistic regression were used to determine if the significant predictors of NAFLD, respectively.

Research results

There were 3235 participants (n = 3235) that passed the exclusion criteria. Based on ultrasound findings, 817 (25.26%) participants were classified as NAFLD. Twenty-four variables were significantly associated with NAFLD in univariate level; the P-value of these significant factors mostly below 0.001. Using multivariate analysis, we found 9 out of 24 factors to be significantly associated with NAFLD. Ranked by ΔR2, the top three factors ranked are waist circumference (OR = 1.03, ΔR2 = 2.13%, P < 0.001), C-peptide level (OR = 1.82, ΔR2 = 1.33%, P < 0.001), and loge of ALT (OR = 1.76, ΔR2 = 1.16%, P < 0.001). The pseudo R2 of the multivariate model is 16.68%.

Research conclusions

C-peptide is the second most important predictor of NAFLD in United States population after waist circumference.

Research perspectives

Further prospective research is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients. Moreover, C-peptide should be considered as a potential factor for calculative liver scores to evaluate the fibrosis level.