Type 2 Diabetes mellitus alters the cargo of (poly)phenol metabolome and the oxidative status in circulating lipoproteins

The incidence of diabetes on the worldwide population has tripled in the past 5 decades. While drug-based therapies are valuable strategies to treat and ease the socio-economic burden of diabetes, nutritional strategies offer valuable alternatives to prevent and manage diabetes onset and contribute to the sustainability of health budgets. Whilst, intervention studies have shown that (poly)phenol-rich diets improve fasting glucose levels and other blood parameters, very little is known about the distribution of ingested polyphenols in circulation and the impact of diabetes on its cargo. In this study we investigate the impact of type 2 diabetes on the cargo of plasma (poly)phenols. Our results show that phenolic compounds are heterogeneously distributed in circulation though mainly transported by lipoprotein populations. We also found that diabetes has a marked effect on the phenolic content transported by VLDL resulting in the decrease in the content of flavonoids and consequently a decrease in the antioxidant capacity. In addition to the reduced bioavailability of (poly)phenol metabolites and increase of oxidative status in LDL and HDL populations in diabetes, cell-based assays show that sub-micromolar amounts of microbial (poly)phenol metabolites are able to counteract the pro-inflammatory status in glucose-challenged endothelial cells. Our findings highlight the relevance of triglyceride-rich lipoproteins in the transport and delivery of bioactive plant-based compounds to the endothelium in T2DM supporting the adoption of nutritional guidelines as an alternative strategy to drug-based therapeutic approaches.