PMID- 31431395
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20200219
IS  - 1590-3729 (Electronic)
IS  - 0939-4753 (Linking)
VI  - 29
IP  - 10
DP  - 2019 Oct
TI  - Greater circulating DPP4 activity is associated with impaired flow-mediated 
      dilatation in adults with type 2 diabetes mellitus.
PG  - 1087-1094
LID - S0939-4753(19)30278-9 [pii]
LID - 10.1016/j.numecd.2019.07.010 [doi]
AB  - BACKGROUND AND AIM: Dipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the 
      regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 
      (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors 
      (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. 
      DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in 
      experimental models. The relationship between DPP4 activity and endothelial 
      function in diabetes has not been explored yet. Aim of this study was to 
      investigate systemic plasma DPP4 activity in relation to endothelial function in 
      patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Sixty-two 
      T2DM individuals were recruited in our Diabetes outpatient clinics, Sapienza 
      University, Rome, Italy. All participants underwent complete clinical work-up; 
      endothelial function was evaluated by flow-mediated dilatation (FMD) test; plasma 
      DPP4 activity was assessed by measuring the 7-amino-4-methylcoumarin (AMC) 
      cleavage rate from the synthetic substrate H-glycyl-prolyl-AMC and compared with 
      DPP4 activity measured in sixty-two age-, sex-, BMI-matched non-diabetic 
      subjects. Patients with T2DM had significantly higher DPP4 activity than 
      non-diabetic individuals (211,466 +/- 87657 vs 158,087 +/- 60267 nmol/min/ml, 
      p < 0.001); in T2DM patients, greater DPP4 activity significantly correlated with 
      lower FMD whereas was not associated with BMI and metabolic control. Greater 
      systemic DPP4 activity was an independent predictor of reduced FMD after 
      adjusting for age, gender and other confounders. CONCLUSIONS: Circulating DPP4 
      activity is increased in individuals with T2DM and associated with signs of 
      endothelial dysfunction such as impaired FMD. DPP4 may negatively affect 
      endothelial function through mechanisms beyond glucose homeostasis and metabolic 
      control.
CI  - Copyright (c) 2019 The Italian Society of Diabetology, the Italian Society for the 
      Study of Atherosclerosis, the Italian Society of Human Nutrition, and the 
      Department of Clinical Medicine and Surgery, Federico II University. All rights 
      reserved.
FAU - Barchetta, Ilaria
AU  - Barchetta I
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Ciccarelli, Gea
AU  - Ciccarelli G
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Barone, Eugenio
AU  - Barone E
AD  - Department of Biochemical Sciences, Sapienza University of Rome, Italy.
FAU - Cimini, Flavia A
AU  - Cimini FA
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Ceccarelli, Valentina
AU  - Ceccarelli V
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Bertoccini, Laura
AU  - Bertoccini L
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Sentinelli, Federica
AU  - Sentinelli F
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Tramutola, Antonella
AU  - Tramutola A
AD  - Department of Biochemical Sciences, Sapienza University of Rome, Italy.
FAU - Del Ben, Maria
AU  - Del Ben M
AD  - Department of Internal Medicine and Medical Specialties, Sapienza University of 
      Rome, Italy.
FAU - Angelico, Francesco
AU  - Angelico F
AD  - Department of Internal Medicine and Medical Specialties, Sapienza University of 
      Rome, Italy.
FAU - Baroni, Marco G
AU  - Baroni MG
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Lenzi, Andrea
AU  - Lenzi A
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy.
FAU - Cavallo, Maria G
AU  - Cavallo MG
AD  - Department of Experimental Medicine, Sapienza University of Rome, Italy. 
      Electronic address: gisella.cavallo@uniroma1.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190723
PL  - Netherlands
TA  - Nutr Metab Cardiovasc Dis
JT  - Nutrition, metabolism, and cardiovascular diseases : NMCD
JID - 9111474
RN  - 0 (Biomarkers)
RN  - EC 3.4.14.5 (DPP4 protein, human)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Brachial Artery/enzymology/*physiopathology
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*blood/diagnosis/enzymology/*physiopathology
MH  - Dipeptidyl Peptidase 4/*blood
MH  - Endothelium, Vascular/enzymology/*physiopathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Rome
MH  - Up-Regulation
MH  - *Vasodilation
OTO - NOTNLM
OT  - Cardiovascular disease
OT  - Dipeptidyl peptidase 4
OT  - Endothelial function
OT  - Type 2 diabetes mellitus
EDAT- 2019/08/23 06:00
MHDA- 2020/02/20 06:00
CRDT- 2019/08/22 06:00
PHST- 2019/02/27 00:00 [received]
PHST- 2019/07/01 00:00 [revised]
PHST- 2019/07/15 00:00 [accepted]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2019/08/22 06:00 [entrez]
AID - S0939-4753(19)30278-9 [pii]
AID - 10.1016/j.numecd.2019.07.010 [doi]
PST - ppublish
SO  - Nutr Metab Cardiovasc Dis. 2019 Oct;29(10):1087-1094. doi: 
      10.1016/j.numecd.2019.07.010. Epub 2019 Jul 23.