Elevated serum advanced glycation endproducts in obese indicate risk for the metabolic syndrome: a link between healthy and unhealthy obesity?

Abstract

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 ((ϵ)N-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, TNFα, 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, may indicate 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.

Figure 1.

A, Dietary AGE intake in MS and non-MS subjects. Daily dietary AGE intake expressed as percentage above that in non-MS subjects taken as 100%. [score 0: non-MS with normal WC; score 1: non-MS with high WC; score 2–4: MS subjects with two or more MS criteria (only one subject displayed all five features of the MS and was not included)]. B, Relationship of serum MG and serum CML in persons with MS (straight line) and non-MS (dashed line). Both parameters were assessed simultaneously and in the fasting state (MS, r = 0.704, P < .001; non-MS, r = 0.733, P < .001). Insets: b1, Relationship of serum CML and iCML in MS subjects. Both parameters were assessed simultaneously and in the fasting state (r = 0.809, P < .001; non-MS). b2, Relationship of sMG and iMG in MS subjects. Both parameters were assessed simultaneously and in the fasting state (r = 0.802, P < .001; non-MS). C, Relationship of fasting serum MG levels and percentage body fat determined (by bioimpedance) in persons with MS (solid line) and non-MS (dashed line). Both parameters were assessed simultaneously and in the fasting state (MS, r = −0.074, P = .414; non-MS, r = 0.174, P = .073). D, Serum MG (sMG) levels according to components of the MS. Data are shown as box plots denoting levels of sMG in persons with or without MS [score 0: non-MS with normal WC; score 1: non-MS with high WC; score 2–4: MS subjects with two or more MS criteria (only one subject displayed all five features of the MS and was not included)]. E, TNFα levels according to components of the MS. Data are shown as box plots denoting TNFα protein measured in PMNCs from each of the groups shown in panel B. Differences of means in panels A, D, and E were not significant (NS) between score 0 and 1 or between score 2, 3, and 4 but were significant between each of scores 2, 3, or 4 and scores 0 and 1.

Figure 2.

Fasting sMG levels plotted against markers of insulin resistance, inflammation, and OS in MS (solid lines) and non-MS subjects (dashed lines) (A–D) and against markers of innate defense mechanisms (E and F). A, sMG vs HOMA (MS: r = 0.464, P < .001; non-MS: r = 0.230; P < .001). B, sMG vs plasma leptin (MS: r = 0.677; P < .001; non-MS: r = 0.262; P = .018). C, 8-Plasma isoprostanes (MS, r = 0.784; P < .001; non-MS, r = 0.594; P < .001). D, PMNC TNFα protein (MS, r = 0.654; P < .001; non-MS, r = 0.489; P < .001). E, sMG vs AGER1 mRNA (MS, r = −0.508; P = .002; non-MS, r = 0.336; P < .001). F, sMG vs SIRT1 mRNA (MS, r = −0.619; P < .001; non-MS, r = −0.255; P = .002).