title: 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.
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Charles Perkins Centre and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia.|NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Williams
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Ana Júlia
authors.initials: AJ
authors.lastname: Vieira De Ribeiro
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Emilia
authors.initials: E
authors.lastname: Prakoso
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Veillard
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Shackel
authors.affiliation: Sydney Nursing School, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Brooks
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Yangmin
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Erika
authors.initials: E
authors.lastname: Cavanagh
authors.affiliation: Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Raleigh
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Charles Perkins Centre and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Susan V
authors.initials: SV
authors.lastname: McLennan
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Keane
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.|St George Hospital, Sydney, New South Wales, Australia.
authors.forename: Amany
authors.initials: A
authors.lastname: Zekry
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Centenary Institute, Sydney, New South Wales, Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
authors.affiliation: Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|Charles Perkins Centre and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D054459:Elasticity Imaging Techniques; D005260:Female; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D009767:Obesity, Morbid / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C488421:KRT18 protein, human; D053538:Keratin-18; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: apoptosis; diabetes; dipeptidyl peptidase-4; fibrosis; non-alcoholic fatty liver disease; 关键词：细胞凋亡，糖尿病，二肽基肽酶-4，纤维化，非酒精性脂肪性肝病