Xue, Mingzhan, Weickert, Martin O., Qureshi, S. A., Kandala, Ngianga-Bakwin, Anwar, Attia, Waldron, Molly, Shafie, Alaa, Messenger, David, Fowler, Mark, Jenkins, Gail, Rabbani, Naila and Thornalley, Paul J. (2016) Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation. Diabetes . db160153. doi:10.2337/db16-0153 ISSN 0012-1797.

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Abstract

Risk of insulin resistance, impaired glycemic control and cardiovascular disease is excessive in overweight and obese populations. We hypothesised that increasing expression of glyoxalase 1 (Glo1) – an enzyme that catalyses the metabolism of reactive metabolite and glycating agent, methylglyoxal – may improve metabolic and vascular health. Dietary bioactive compounds were screened for Glo1 inducer activity in a functional reporter assay, hits confirmed in cell culture and an optimised Glo1 inducer formulation evaluated in a randomised, placebo-controlled crossover clinical trial in 29 overweight and obese subjects. We found trans-resveratrol (tRES) and hesperetin (HESP), at concentrations achieved clinically, synergised to increase Glo1 expression. In highly overweight subjects (BMI >27.5 kg/m2), tRES-HESP co-formulation increased expression and activity of Glo1 (+ 27%. P<0.05), decreased plasma methylglyoxal (-37%, P<0.05) and total body methylglyoxal-protein glycation (-14%, P<0.01). It decreased fasting and postprandial plasma glucose (-5%, P<0.01 and – 6%, P<0.03, respectively), increased Oral Glucose Insulin Sensitivity index (+42 mlmin-1m-2, P<0.02) and improved arterial dilatation ΔFMD/ΔGTND (95%CI 0.13–2.11). In all subjects, it decreased vascular inflammation marker sICAM-1 (-10%, P<0.01). In previous clinical evaluations, tRES and HESP individually were ineffective. tRES-HESP co-formulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese populations.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Insulin resistance, Cardiovascular system -- Diseases, Glyoxalase , Glycosylation, Obesity, Metabolism
Journal or Publication Title:	Diabetes
Publisher:	American Diabetes Association
ISSN:	0012-1797
Official Date:	10 May 2016
Dates:	Date Event 10 May 2016 Available 27 April 2016 Accepted 2 February 2016 Submitted
Article Number:	db160153
DOI:	10.2337/db16-0153
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	13 May 2016
Date of first compliant Open Access:	13 May 2016
Funder:	Unilever (Firm), Innovate UK
Grant number:	(Project no 101129).

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