The study demonstrated the compounds’ effectiveness in lowering blood sugar levels and insulin resistance at a rate that surpasses current pharmaceutical interventions.
As well as helping to treat diabetes, their potency could also provide benefits for patients with obesity and high risk of heart disease.
Researchers from Warwick University hypothesised that increasing the action of the enzyme glyoxalase 1 (Glo1) would improve metabolic and vascular health.
Glo1’s main function is to catalyse the metabolism of reactive metabolites and methylglyoxal (MG), a compound identified as binding directly to nerve endings, increasing the chronic soreness experienced in diabetic neuropathy.
Fruit compounds
Part of the researcher’s hypothesis focused on the mechanisms of action trans-resveratrol (tRES) – found in red grapes, and hesperetin (HESP) – found in oranges, exerted on Glo1.
They believed their effect on Glo1 would decrease levels of MG, improving the health of the overweight and likely help patients with diabetes too.
It has already been proven experimentally that blocking MG improves health impairment in obesity and type 1 and type 2 diabetes.
Researchers enrolled 32 overweight and obese people aged 18-80, who had a BMI between 25-40.
These subjects were given a supplement containing tRES and HESP once a day for eight weeks and asked to fill in a food intake questionnaire. Participants were asked to keep physical activity levels unchanged.
Changes to sugar levels were monitored via blood samples whilst artery health, measured by artery wall flexibility, was assessed by analysis of blood markers.
Results indicated that tRES and HESP at certain concentrations increased Glo1 activity. In highly overweight subjects (BMI >27.5 kg/m2), the tRES-HESP combination increased Glo1 activity, and decreased methylglyoxal concentrations in the blood.
Additionally, fasting and postprandial plasma glucose (-5% and -6%) decreased whilst insulin sensitivity increased (+42 ml/min-1m-2). In all subjects, the presence of the vascular inflammation marker sICAM-1 was down by 10%.
“Glo1 deficiency has been identified as a driver of health problems in obesity, diabetes and cardiovascular disease,” said Paul Thornalley, professor in Systems Biology at Warwick Medical School.
“The key steps to discovery were to focus on increasing Glo1 and then to combine tRES and HESP together in the formulation for effective treatment.”
“As exciting as our breakthrough is it is important to stress that physical activity, diet, other lifestyle factors and current treatments should be adhered to.”
Methylglyoxal toxicity
Previous studies investigating methylglyoxal in diabetes and its resulting complications have established its role especially in diabetic-associated vascular diseases.
Additional studies have already demonstrated that diabetics have MG levels two- to four-fold higher in circulation.
The rate of methylglyoxal detoxification is lower than the rate of its production and inevitably MG accumulates in cells and becomes toxic.
Source: Diabetes
Published online ahead of print, doi: 10.2337/db16-0153
“Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation.”
Authors: Mingzhan Xue et al.