Advanced Glycation Endproducts clinical trials

Restriction of Dietary AGEs to Prevent Diabetes in Overweight Individuals

Current efforts to arrest the epidemic of type 2 diabetes mellitus (T2DM) have had limited success. Thus there is an urgent need for effective approaches to prevent the development of T2DM. It is widely accepted that the current epidemic is driven by an increase in global food abundance and reduced food quality, making changes in diet a key determinant of the T2DM epidemic. Dietary factors can affect cardio-metabolic health; among these factors, advanced glycation end-products (AGEs) in food are potential risk factors for insulin resistance and T2DM. AGEs are a heterogeneous group of unavoidable stable bioactive compounds. Endogenous formation of AGEs is a continuous naturally occurring process, and is the result of normal metabolism. However, increased formation of AGEs occurs during ageing and under hyperglycaemic conditions. AGEs are implicated in the development of diabetes and vascular complications. Over the past several decades, methods of food processing have changed and meals now contain excess fat and sugar and are most susceptible for the formation of AGEs. In addition, AGEs in food are highly desirable due to their profound effect on shelf life, sterility, flavour, colour, and thus food consumption. Hence, a substantial portion of AGEs are derived from exogenous sources, particularly food. These exogenous AGEs are potential risk factors for insulin resistance and the development of T2DM. The investigators recently found that dietary AGEs represent a significant source of circulating AGEs, and have similar pathogenic properties compared to their endogenous counterparts including the development of insulin resistance and T2DM. Taken together, dietary AGEs are proposed to play a pivotal role in the development and progression of T2DM and its complications. Reduction of dietary intake of AGEs may therefore be an alternative strategy to reduce the risk of vascular disease and insulin resistance. The investigators therefore hypothesize that dietary restriction of AGEs in overweight individuals improves insulin sensitivity, β-cell function, and vascular function.