Application of dietary supplements in the prevention of type 2 diabetes-related cardiovascular complications

Joint review by the Leicester Institute for Pharmaceutical Innovation and the Institute for Allied Health Sciences Research, based on invited plenary lecture presented by Prof. Randolph Arroo at the conference 'Natural Products in Drug Discovery and Human Health' in Lisbon, 28-31 July, 2019 The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Type 2 diabetes, which accounts for the vast majority of diabetes worldwide is the result of a lowered sensitivity of the insulin receptors, resulting in impaired sugar metabolism is and chronic hyperglycaemia. There is no cure for type 2 diabetes, though some people with pre-diabetes and diabetes manage to reach and hold normal blood sugar levels, thus avoiding most of the complications that come with chronic hyperglycaemia; this is sometimes referred to as ‘reversing diabetes’. A healthy diet, with sufficient amounts of fruits, nuts, and vegetables is positively correlated with maintaining glycaemic control and prevention of diabetes-related complications. Whereas many different dietary phytochemicals have been considered to play a role in the glycaemic control and in prevention of degenerative diseases, there is currently no consensus on a particular mode of action. In this review, a range of pre-clinical studies and intervention studies, including randomised double-blind, placebo controlled clinical studies, are considered that investigate the role of dietary compounds in the prevention of type 2 diabetes-related complications. Three generic mechanisms of action can be discerned: compounds that reduce sugar uptake, compounds that restore insulin function, and compounds that attenuate the effects of oxidative stress and chronic inflammation. Particularly the latter has received wide attention in the form of activation of the Nrf2-antioxidant response element signalling pathway by various polyphenolic or triterpenoid compounds. Although individual reports may present models with clear looking signalling cascades, an overall review shows that many biologically active compounds in the human diet are pan assay interference substances that alter several cell functions simultaneously, which makes them less attractive for drug development