Risk of insulin resistance, impaired glycemic control, and cardiovascular disease is excessive in overweight and obese populations. We hypothesized that increasing expression of glyoxalase 1 (Glo1)-an enzyme that catalyzes 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 were confirmed in cell culture, and an optimized Glo1 inducer formulation was evaluated in a randomized, placebo-controlled crossover clinical trial in 29 overweight and obese subjects. We found trans-resveratrol (tRES) and hesperetin (HESP), at concentrations achieved clinically, synergized to increase Glo1 expression. In highly overweight subjects (BMI >27.5 kg/m 2 ), tRES-HESP coformulation increased expression and activity of Glo1 (27%, P < 0.05) and decreased plasma methylglyoxal (237%, P < 0.05) and total body methylglyoxal-protein glycation (214%, P < 0.01). It decreased fasting and postprandial plasma glucose (25%, P < 0.01, and 28%, P < 0.03, respectively), increased oral glucose insulin sensitivity index (42 mL $ min 21 $ m 22, P < 0.02), and improved arterial dilatation Dbrachial artery flowmediated dilatation/Ddilation response to glyceryl nitrate (95% CI 0.13-2.11). In all subjects, it decreased vascular inflammation marker soluble intercellular adhesion molecule-1 (210%, P < 0.01). In previous clinical evaluations, tRES and HESP individually were ineffective. tRES-HESP coformulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese populations.

ObjectivesTo investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).DesignCross-sectional study.SettingUniversity Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence.ParticipantsPatients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities.Main outcome measureTo identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment.ResultsMUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients.ConclusionsGiven the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.