Postprandial insulin secretion pattern is associated with histological severity in non-alcoholic fatty liver disease patients without prior known diabetes mellitus.
OBJECTIVE
Insulin resistance and diabetes mellitus (DM) are known to contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, the relationship between glucose metabolism and NAFLD is not well known. In this study, we investigated whether secretion patterns of glucose and insulin could influence the histological severity in NAFLD patients without prior known type 2 DM.


METHODS
A 75-g glucose tolerance test was performed on 173 biopsy-proven NAFLD patients without prior known type 2 DM. Plasma glucose and insulin levels were analyzed periodically for 3 h after oral glucose loading.


RESULTS
Of the 173 NAFLD patients, 168 had non-alcoholic steatohepatitis, whereas no patient had cirrhosis. Irrespective of the hemoglobin A1c levels, impaired glucose tolerance, including DM, was detected in 60% of the NAFLD patients. While the secretion pattern of glucose after glucose loading was similar among the NAFLD patients, postprandial insulin levels increased and delayed insulin secretion increased in severity in parallel with the aggravation of histological findings (fibrosis stages). Factors associated with advanced fibrosis were higher insulin levels at 120 min after oral glucose loading (P = 0.0001; odds ratio [OR], 3.56; 95% confidence interval [CI], 1.61-7.86), aspartate aminotransferase (P = 0.003; OR, 2.70; 95% CI: 1.19-6.12), and age (P = 0.02; OR, 2.49; 95% CI: 1.15-5.37) as determined by multivariate analysis.


CONCLUSIONS
Postprandial hyperinsulinemia (but not glucose levels) was associated with advanced fibrosis. The oral glucose tolerance test should be considered in NAFLD patients without prior known type 2 DM in order to facilitate early therapeutic intervention.
Department of Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Yuki
Y
Kimura
Hideyuki
H
Hyogo
Tomokazu
T
Ishitobi
Yoshitaka
Y
Nabeshima
Koji
K
Arihiro
Kazuaki
K
Chayama
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007564:Japan; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D016017:Odds Ratio; D019518:Postprandial Period; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin