Objective The correlation between the insulin secretion levels and the risk of hepatocarcinogenesis is clinically important. The aim of the present study was to determine the effects of various clinical parameters on
C-peptide (
CPR) levels in patients with
non-alcoholic fatty liver disease (
NAFLD). Methods In this retrospective cohort study, the effects of clinical parameters on
insulin resistance (HOMA-IR) and insulin secretion levels (HOMA-β and fasting
CPR) were investigated. Patients A total of 244 Japanese patients with histopathologically confirmed
NAFLD were evaluated. Of these, 77 underwent the meal tolerance test (MTT) to evaluate the association of various clinical parameters with the
CPR levels at 120 minutes. Results A multivariate analysis identified fasting plasma
glucose (FPG) (≥110 mg/dL),
aspartate aminotransferase (≥1.0×ULN IU/L), and a large waist circumference as independent predictors of
insulin resistance (HOMA-IR ≥2.5) or high fasting
CPR levels. Significant parameters for a low insulin secretion capacity (HOMA-β <30%) were not detected, except for the parameters mentioned in the diagnostic criteria of
diabetes mellitus. Regarding the MTT, the
CPR levels at 120 minutes were significantly higher in patients with
fibrosis stage 3-4 than in those with stage 0-2. Body composition and genetic variation did not affect the
CPR levels at 120 minutes. A multivariate analysis identified
fibrosis stage (3-4),
hyperuricemia, FPG (≥110 mg/dL), and
procollagen III
peptide (>1.0 U/mL) as independent predictors of high
CPR levels at 120 minutes. Conclusion The present study showed that high plasma
glucose levels and severe
liver fibrosis stage influence insulin secretion levels in Japanese patients with
NAFLD. Conservation of delayed insulin secretion levels was confirmed in patients with severe
liver fibrosis.