Elevated Serum Advanced Glycation Endproducts in Obese Indicate Risk for the Metabolic Syndrome: A Link Between Healthy and Unhealthy Obesity?

Context: Although obesity can predispose to the metabolic syndrome (MS), diabetes, and cardiovascular disease, not all obese subjects develop MS, hence the need for new indicators of risk for this syndrome. Advanced glycation end products (AGEs) correlate with factors involved in the MS, including inflammation and insulin resistance (IR). Because AGEs can be derived from food and are modifiable, it is important to determine whether they are a risk factor for MS. Objective: The objective of this study was to assess the association of endogenous and exogenous AGEs with MS criteria. Design: The following data were collected in a cross-sectional study of subjects with and without the MS: serum AGEs (sAGEs) and mononuclear cell AGEs, metabolites, pro-and antiinflammatory markers, body fat mass measures, including abdominal magnetic resonance imaging, and caloric and dietary AGE (dAGE) consumption. Setting: The study was conducted in the general community. Participants: Participants included 130 MS and 139 non-MS subjects of both sexes, older than 50 years. Results: sAGEs (N-epsilon-carboxymethyllysine, methylglyoxal) were markedly elevated in obese persons with more than one other MS criteria but not in obese without MS criteria. sAGEs directly correlated with markers of IR (HOMA) and inflammation (leptin, TNF alpha, RAGE) and inversely with innate defenses (SIRT1, AGE receptor 1 [AGER1], glyoxalase-I, adiponectin). sAGEs correlated with dAGEs but not with calories, nutrient consumption, or fat mass measures. Consumption of dAGE, but not of calories, was markedly higher in MS than in non-MS. Conclusion: High sAGEs, a modifiable risk factor for IR, mayindicate risk for the MS, type 2 diabetes, and cardiovascular disease. High dietary AGE consumption and serum AGE levels may link healthy obesity to at-risk obesity.