Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3663
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
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.
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.
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.
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.
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%.
C-peptide is the second most important predictor of NAFLD in United States population after waist circumference.
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.