Circulating dipeptidyl peptidase-4 activity correlates with measures of hepatocyte apoptosis and fibrosis in non-alcoholic fatty liver disease in type 2 diabetes mellitus and obesity: A dual cohort cross-sectional study.

Abstract:

BACKGROUND:Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few studies have examined associations between cDPP4 activity and NAFLD severity in humans. This study aimed to examine the relationship of cDPP4 activity with measures of liver disease severity in NAFLD in subjects with diabetes and/or obesity. METHODS:cDPP4 was measured in 106 individuals with type 2 diabetes who had transient elastography (Cohort 1) and 145 individuals with morbid obesity who had liver biopsy (Cohort 2). Both cohorts had caspase-cleaved keratin-18 (ccK18) measured as a marker of apoptosis. RESULTS:Natural log increases in cDPP4 activity were associated with increasing quartiles of ccK18 (Cohorts 1 and 2) and with median liver stiffness ≥10.3 kPa (Cohort 1) and significant fibrosis (F ≥ 2) on liver biopsy (Cohort 2). CONCLUSIONS:In diabetes and/or obesity, cDPP4 activity is associated with current apoptosis and liver fibrosis. Given the pathogenic mechanisms by which DPP4 may progress NAFLD, measurement of cDPP4 activity may have utility to predict disease progression and DPP4 inhibition may improve liver histology over time.

journal_name

J Diabetes

journal_title

Journal of diabetes

authors

Williams KH,Vieira De Ribeiro AJ,Prakoso E,Veillard AS,Shackel NA,Brooks B,Bu Y,Cavanagh E,Raleigh J,McLennan SV,McCaughan GW,Keane FM,Zekry A,Gorrell MD,Twigg SM

doi

10.1111/1753-0407.12237

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

809-19

issue

6

eissn

1753-0393

issn

1753-0407

journal_volume

7

pub_type

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