PMID- 29773079
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20221207
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 17
IP  - 1
DP  - 2018 May 17
TI  - Effects of linagliptin on endothelial function and postprandial lipids in 
      coronary artery disease patients with early diabetes: a randomized, 
      placebo-controlled, double-blind trial.
PG  - 71
LID - 10.1186/s12933-018-0716-x [doi]
LID - 71
AB  - BACKGROUND: Early glucose lowering intervention in subjects with type 2 diabetes 
      mellitus was demonstrated to be beneficial in terms of micro- and macrovascular 
      risk reduction. However, most of currently ongoing cardiovascular outcome trials 
      are performed in subjects with manifest atherosclerosis and long-standing 
      diabetes. Therefore, the aim of this study is to investigate the effects of the 
      dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery 
      disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of 
      cardiovascular surrogate measurements. METHODS: In this randomized, 
      placebo-controlled, double-blind, single-center study, we included subjects with 
      early diabetes (postchallenge diabetes (2 h glucose > 200 mg/dl) or T2DM treated 
      with diet only or on a stable dose of metformin monotherapy and an 
      HbA1c < 75 mmol/mol) and established CAD. Participants were randomized to receive 
      either linagliptin (5 mg) once daily orally or placebo for 12 weeks. The primary 
      outcome was the change in flow mediated dilatation (FMD). The secondary objective 
      was to investigate the effect of linagliptin treatment on arginine 
      bioavailability ratios [Global arginine bioavailability ratio (GABR) and arginine 
      to ornithine ratio (AOR)]. Arginine, ornithine and citrulline were measured in 
      serum samples with a conventional usual amino acid analysis technique, involving 
      separation of amino acids by ion exchange chromatography followed by postcolumn 
      continuous reaction with ninhydrin. GABR was calculated by L-arginine divided by 
      the sum of (L-ornithine plus L-citrulline). The AOR was calculated by dividing 
      L-arginine by L-ornithine levels. Group comparisons were calculated by using a 
      two-sample t-test with Satterthwaite adjustment for unequal variances. RESULTS: 
      We investigated 43 patients (21% female) with a mean age of 63.3 +/- 8.2 years. FMD 
      at baseline was 3.5 +/- 3.1% in the linagliptin group vs. 4.0 +/- 2.9% in the placebo 
      group. The change in mean FMD in the linagliptin group was not significantly 
      different compared to the change in the placebo group (0.43 +/- 4.84% vs. 
      - 0.45 +/- 3.01%; p = 0.486). No significant improvements were seen in the arginine 
      bioavailability ratios (GABR; p = 0.608 and AOR; p = 0.549). CONCLUSION: 
      Linagliptin treatment in subjects with CAD and early T2DM did not improve 
      endothelial function or the arginine bioavailability ratios. Trial registration 
      ClinicalTrials.gov, NCT02350478 ( https://clinicaltrials.gov/ct2/show/NCT02350478 
      ).
FAU - Tripolt, Norbert J
AU  - Tripolt NJ
AD  - Cardiovascular Diabetology Research Group, Division of Endocrinology and 
      Diabetology, Department of Internal Medicine, Medical University of Graz, 
      Auenbruggerplatz 15, 8036, Graz, Austria.
FAU - Aberer, Felix
AU  - Aberer F
AD  - Cardiovascular Diabetology Research Group, Division of Endocrinology and 
      Diabetology, Department of Internal Medicine, Medical University of Graz, 
      Auenbruggerplatz 15, 8036, Graz, Austria.
FAU - Riedl, Regina
AU  - Riedl R
AD  - Institute for Medical Informatics, Statistics and Documentation, Medical 
      University of Graz, Graz, Austria.
FAU - Url, Jasmin
AU  - Url J
AD  - Cardiovascular Diabetology Research Group, Division of Endocrinology and 
      Diabetology, Department of Internal Medicine, Medical University of Graz, 
      Auenbruggerplatz 15, 8036, Graz, Austria.
FAU - Dimsity, Gudrun
AU  - Dimsity G
AD  - Division of Angiology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Meinitzer, Andreas
AU  - Meinitzer A
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, Graz, Austria.
FAU - Stojakovic, Tatjana
AU  - Stojakovic T
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, Graz, Austria.
FAU - Aziz, Faisal
AU  - Aziz F
AD  - Cardiovascular Diabetology Research Group, Division of Endocrinology and 
      Diabetology, Department of Internal Medicine, Medical University of Graz, 
      Auenbruggerplatz 15, 8036, Graz, Austria.
AD  - Center for Biomarker Research in Medicine, CBmed, Graz, Austria.
FAU - Hodl, Ronald
AU  - Hodl R
AD  - Center for Cardiovascular Rehabilitation St. Radegund, St. Radegund, Austria.
FAU - Brachtl, Gabriele
AU  - Brachtl G
AD  - Experimental & Clinical Cell Therapy Institute, Spinal Cord & Tissue Regeneration 
      Center Salzburg, Paracelsus Private Medical University, Salzburg, Austria.
FAU - Strunk, Dirk
AU  - Strunk D
AD  - Experimental & Clinical Cell Therapy Institute, Spinal Cord & Tissue Regeneration 
      Center Salzburg, Paracelsus Private Medical University, Salzburg, Austria.
FAU - Brodmann, Marianne
AU  - Brodmann M
AD  - Division of Angiology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Hafner, Franz
AU  - Hafner F
AD  - Division of Angiology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Sourij, Harald
AU  - Sourij H
AD  - Cardiovascular Diabetology Research Group, Division of Endocrinology and 
      Diabetology, Department of Internal Medicine, Medical University of Graz, 
      Auenbruggerplatz 15, 8036, Graz, Austria. ha.sourij@medunigraz.at.
AD  - Center for Biomarker Research in Medicine, CBmed, Graz, Austria. 
      ha.sourij@medunigraz.at.
LA  - eng
SI  - ClinicalTrials.gov/NCT02350478
GR  - 15941/Oesterreichische Nationalbank/International
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180517
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Lipids)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 29VT07BGDA (Citrulline)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - 94ZLA3W45F (Arginine)
RN  - E524N2IXA3 (Ornithine)
SB  - IM
MH  - Aged
MH  - Arginine/blood
MH  - Austria
MH  - Biomarkers/blood
MH  - Blood Glucose/*drug effects/metabolism
MH  - Citrulline/blood
MH  - Coronary Artery Disease/blood/diagnosis/*drug therapy/physiopathology
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/physiopathology
MH  - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Endothelium, Vascular/*drug effects/metabolism/physiopathology
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Linagliptin/adverse effects/*therapeutic use
MH  - Lipids/*blood
MH  - Male
MH  - Middle Aged
MH  - Ornithine/blood
MH  - Postprandial Period
MH  - Prospective Studies
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vasodilation/*drug effects
PMC - PMC5958406
OTO - NOTNLM
OT  - Coronary artery disease
OT  - DPP-4 inhibitor
OT  - Endothelial function
OT  - Flow mediated dilatation
OT  - Linagliptin
OT  - RCT
OT  - Type 2 diabetes
EDAT- 2018/05/19 06:00
MHDA- 2019/01/29 06:00
PMCR- 2018/05/17
CRDT- 2018/05/19 06:00
PHST- 2018/02/27 00:00 [received]
PHST- 2018/05/10 00:00 [accepted]
PHST- 2018/05/19 06:00 [entrez]
PHST- 2018/05/19 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2018/05/17 00:00 [pmc-release]
AID - 10.1186/s12933-018-0716-x [pii]
AID - 716 [pii]
AID - 10.1186/s12933-018-0716-x [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2018 May 17;17(1):71. doi: 10.1186/s12933-018-0716-x.