A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals.

BACKGROUNDAccumulation of advanced glycation endproducts (AGEs) may contribute to the pathophysiology of type 2 diabetes and its vascular complications. AGEs are widely present in food, but whether restricting AGE intake improves risk factors for type 2 diabetes and vascular dysfunction is controversial.METHODSAbdominally obese but otherwise healthy individuals were randomly assigned to a specifically designed 4-week diet low or high in AGEs in a double-blind, parallel design. Insulin sensitivity, secretion, and clearance were assessed by a combined hyperinsulinemic-euglycemic and hyperglycemic clamp. Micro- and macrovascular function, inflammation, and lipid profiles were assessed by state-of-the-art in vivo measurements and biomarkers. Specific urinary and plasma AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were assessed by mass spectrometry.RESULTSIn 73 individuals (22 males, mean ± SD age and BMI 52 ± 14 years, 30.6 ± 4.0 kg/m2), intake of CML, CEL, and MG-H1 differed 2.7-, 5.3-, and 3.7-fold between the low- and high-AGE diets, leading to corresponding changes of these AGEs in urine and plasma. Despite this, there was no difference in insulin sensitivity, secretion, or clearance; micro- and macrovascular function; overall inflammation; or lipid profile between the low and high dietary AGE groups (for all treatment effects, P > 0.05).CONCLUSIONThis comprehensive RCT demonstrates very limited biological consequences of a 4-week diet low or high in AGEs in abdominally obese individuals.TRIAL REGISTRATIONClinicaltrials.gov, NCT03866343; trialregister.nl, NTR7594.FUNDINGDiabetesfonds and ZonMw.

Habitual Intake of Dietary Advanced Glycation End Products Is Not Associated with Arterial Stiffness of the Aorta and Carotid Artery in Adults: The Maastricht Study.

BACKGROUND: Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to arterial stiffness, which in turn is a causal factor in the pathogenesis of stroke, myocardial infarction, and heart failure. Whether AGEs derived from food also contribute to arterial stiffness is not clear. OBJECTIVES: We investigated whether higher intake of dietary AGEs is associated with arterial stiffness. METHODS: In this cross-sectional observational study in 2255 participants of The Maastricht Study (mean ± SD age: 60 ± 8 y, 51% male, mean ± SD BMI: 26.9 ± 4.4 kg/m2, n = 1326 normal glucose metabolism, n = 341 prediabetes, and n = 585 type 2 diabetes mellitus), we estimated intake of the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) by a validated FFQ coupled to our ultra-performance liquid chromatography tandem mass spectrometry dietary AGE database. Arterial stiffness was determined using carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and carotid Young's elastic modulus (YEM). We performed multiple linear regression analyses adjusting for potential confounders (demographic, hemodynamic, cardiovascular, and dietary factors). RESULTS: In the fully adjusted models we observed no statistically significant associations between intake of the dietary AGEs CML, CEL, and MG-H1 and arterial stiffness expressed as cfPWV, carotid DC, and carotid YEM. CONCLUSIONS: In adults aged 40-75 y, habitual intake of the dietary AGEs CML, CEL, and MG-H1 is not associated with arterial stiffness measured as cfPWV, carotid DC, or carotid YEM.