RT Journal Article
SR Electronic
T1 Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus
JF Open Heart
JO Open Heart
FD British Cardiovascular Society
SP e000647
DO 10.1136/openhrt-2017-000647
VO 4
IS 2
A1 Radzi M Noh
A1 Sowmya Venkatasubramanian
A1 Shruti Daga
A1 Jeremy Langrish
A1 Nicholas L Mills
A1 Ninian N Lang
A1 Ethan Hoffmann
A1 Brian Waterhouse
A1 David E Newby
A1 Brian M Frier
YR 2017
UL http://openheart.bmj.com/content/4/2/e000647.abstract
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.