title: Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.
abstract: BACKGROUND
  In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL).
  
  
  RESULTS
  sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82 type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs) controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes"), 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests); NAFLD(NGTonly): 3.23 (p = 0.0013 vs CNTRL); NAFLD(IFG/IGT/type 2 diabetes): 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group). sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L) and abnormal glucose metabolism (30.38U/L) than in CNTRL (25.89U/L, p<0.001 and p = 0.013) or in T2D groups (23.97U/L, p<0.001 and p = 0.004). Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210.
  
  
  CONCLUSIONS
  The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly suggests that serum DPP-4 activity should be considered as a novel liver disease biomarker.
authors.affiliation: Department of Medicine, Semmelweis University, Budapest, Hungary. firneisz@bel2.sote.hu
authors.forename: Gábor
authors.initials: G
authors.lastname: Firneisz
authors.forename: Tímea
authors.initials: T
authors.lastname: Varga
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lengyel
authors.forename: János
authors.initials: J
authors.lastname: Fehér
authors.forename: Dóra
authors.initials: D
authors.lastname: Ghyczy
authors.forename: Barna
authors.initials: B
authors.lastname: Wichmann
authors.forename: László
authors.initials: L
authors.lastname: Selmeci
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
authors.forename: Anikó
authors.initials: A
authors.lastname: Somogyi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000378:metabolism*; D005215:Fasting; D005234:Fatty Liver / Q000097:blood* / Q000201:enzymology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000201:enzymology
chemical_list: D015415:Biomarkers; D018819:Dipeptidyl Peptidase 4
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