PMID- 28912956
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220129
IS  - 2053-3624 (Print)
IS  - 2053-3624 (Electronic)
IS  - 2053-3624 (Linking)
VI  - 4
IP  - 2
DP  - 2017
TI  - Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 
      2 diabetes mellitus.
PG  - e000647
LID - 10.1136/openhrt-2017-000647 [doi]
LID - e000647
AB  - BACKGROUND: The cardiometabolic effects of SRT2104, a novel SIRT1 activator, were 
      investigated in people with type 2 diabetes mellitus (T2DM). METHODS: Fifteen 
      adults with T2DM underwent a randomised, double-blind, placebo-controlled 
      cross-over trial and received 28 days of oral SRT2104 (2.0 g/day) or placebo. 
      Forearm vasodilatation (measured during intrabrachial bradykinin, acetylcholine 
      and sodium nitroprusside infusions) as well as markers of glycaemic control, 
      lipid profile, plasma fibrinolytic factors, and markers of platelet-monocyte 
      activation, were measured at baseline and at the end of each treatment period. 
      RESULTS: Lipid profile and platelet-monocyte activation were similar in both 
      treatment arms (p>0.05 for all). Forearm vasodilatation was similar on exposure 
      to acetylcholine and sodium nitroprusside (p>0.05, respectively). 
      Bradykinin-induced vasodilatation was less during treatment with SRT2104 versus 
      placebo (7.753vs9.044, respectively, mean difference=-1.291,(95% CI -2.296 to 
      -0.285, p=0.012)). Estimated net plasminogen activator inhibitor type 1 antigen 
      release was reduced in the SRT2104 arm versus placebo (mean 
      difference=-38.89 ng/100 mL tissue/min, (95% CI -75.47, to -2.305, p=0.038)). 
      There were no differences in other plasma fibrinolytic factors (p>0.05 for all). 
      After 28 days, SRT2104 exposure was associated with weight reduction (-0.93 kg 
      (95% CI -1.72 to -0.15), p=0.0236), and a rise in glycated haemoglobin (5 
      mmol/mol or 0.48% (0.26 to 0.70), p=0.004). CONCLUSIONS: In people with T2DM, 
      SRT2104 had inconsistent, predominantly neutral effects on endothelial and 
      fibrinolytic function, and no discernible effect on lipids or platelet function. 
      In contrast, weight loss was induced along with deterioration in glycaemic 
      control, suggestive of potentially important metabolic effects. CLINICAL TRIAL 
      REGISTRATION: NCT01031108; Results.
FAU - Noh, Radzi M
AU  - Noh RM
AD  - Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK.
FAU - Venkatasubramanian, Sowmya
AU  - Venkatasubramanian S
AD  - Department of Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
FAU - Daga, Shruti
AU  - Daga S
AD  - Clinical Development, GSK, Surrey, UK.
FAU - Langrish, Jeremy
AU  - Langrish J
AD  - Department of Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
FAU - Mills, Nicholas L
AU  - Mills NL
AD  - Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK.
FAU - Lang, Ninian N
AU  - Lang NN
AD  - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
FAU - Hoffmann, Ethan
AU  - Hoffmann E
AD  - Research and Development, GlaxoSmithKline, Philadelphia, Pennsylvania, USA.
FAU - Waterhouse, Brian
AU  - Waterhouse B
AD  - Research and Development, GlaxoSmithKline, Philadelphia, Pennsylvania, USA.
FAU - Newby, David E
AU  - Newby DE
AD  - Division of Health Sciences, Centre for Cardiovascular Sciences, University of 
      Edinburgh, Edinburgh, Edinburgh, UK.
FAU - Frier, Brian M
AU  - Frier BM
AD  - Department of Diabetes, Royal Infirmary Edinburgh, NHS Lothian, Edinburgh, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT01031108
GR  - Wellcome Trust/United Kingdom
GR  - FS/16/14/32023/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170902
PL  - England
TA  - Open Heart
JT  - Open heart
JID - 101631219
PMC - PMC5588958
OTO - NOTNLM
OT  - SIRT-1 activator
OT  - cardiovascular risk
OT  - endothelial dysfunction
OT  - lipids
OT  - platelet activation
OT  - sirtuins
OT  - type 2 diabetes mellitus
OT  - weight loss
COIS- Competing interests: None declared.
EDAT- 2017/09/16 06:00
MHDA- 2017/09/16 06:01
PMCR- 2017/09/02
CRDT- 2017/09/16 06:00
PHST- 2017/04/21 00:00 [received]
PHST- 2017/07/28 00:00 [revised]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/09/16 06:00 [entrez]
PHST- 2017/09/16 06:00 [pubmed]
PHST- 2017/09/16 06:01 [medline]
PHST- 2017/09/02 00:00 [pmc-release]
AID - openhrt-2017-000647 [pii]
AID - 10.1136/openhrt-2017-000647 [doi]
PST - epublish
SO  - Open Heart. 2017 Sep 2;4(2):e000647. doi: 10.1136/openhrt-2017-000647. 
      eCollection 2017.