title: The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients.
abstract: OBJECTIVE
  Dipeptidyl peptidase (DPP)-4 in responsible for incretin degradation and some observations suggest that DPP-4 activity is increased in type 2 diabetes (T2D). We aimed to assess the effect of T2D and glucose control on DPP-4 activity.
  
  
  METHODS
  In the first set (SET1) of patients, we compared plasma DPP-4 activity between 30 T2D and 20 age- and sex-matched non-diabetic subjects. In the second set (SET2), we measured serum DPP-4 activity in 42 T2D patients before and after a trial of glucose control achieved by add-on basal insulin therapy (NCT00699686). Serum/plasma DPP-4 activity was determined using chromogenic and fluorigenic substrates, as well as several positive and negative controls.
  
  
  RESULTS
  In SET1, plasma DPP-4 activity was significantly higher in T2D vs. controls (32.2 ± 1.2 U/l vs. 21.2 ± 1.1 U/l, p < 10(-6)). From a meta-analysis of the literature, we found that T2D is associated with a 33% increase in DPP-4 activity compared to controls. In SET2, serum DPP-4 activity was not lowered by intensified glucose control, despite an average haemoglobin A1c (HbA1c) reduction of 1.5%. In both sets of diabetic patients, the use of metformin was associated with a significantly lower DPP-4 activity, independently of age, sex, body mass index and HbA1c.
  
  
  CONCLUSIONS
  DPP-4 activity is increased in T2D, but is not lowered by glucose control, suggesting that hyperglycaemia is not a direct determinant of DPP-4 activity. However, metformin may indirectly reduce DPP-4 activity.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy. gianpaolo.fadini@unipd.it
authors.forename: Gian P
authors.initials: GP
authors.lastname: Fadini
authors.forename: M
authors.initials: M
authors.lastname: Albiero
authors.forename: L
authors.initials: L
authors.lastname: Menegazzo
authors.forename: S V
authors.initials: SV
authors.lastname: de Kreutzenberg
authors.forename: A
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D054795:Incretins / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D008687:Metformin; C517652:hemoglobin A1c protein, human