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
| Autor: | Kathryn H, Williams, Ana Júlia, Vieira De Ribeiro, Emilia, Prakoso, Anne-Sophie, Veillard, Nicholas A, Shackel, Belinda, Brooks, Yangmin, Bu, Erika, Cavanagh, Jim, Raleigh, Susan V, McLennan, Geoffrey W, McCaughan, Fiona M, Keane, Amany, Zekry, Mark D, Gorrell, Stephen M, Twigg |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Liver Cirrhosis Male Keratin-18 Biopsy Dipeptidyl Peptidase 4 Apoptosis Middle Aged Prognosis Severity of Illness Index Obesity Morbid Cohort Studies Cross-Sectional Studies Diabetes Mellitus Type 2 Non-alcoholic Fatty Liver Disease Predictive Value of Tests Risk Factors Hepatocytes Elasticity Imaging Techniques Humans Female Biomarkers Aged |
| Zdroj: | Journal of diabetes. 7(6) |
| ISSN: | 1753-0407 |
| Popis: | 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.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.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).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. |
| Databáze: | OpenAIRE |
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