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

Abstract

Background: Accumulation 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. Research design and methods: Abdominally 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 profile were assessed by state-of-art in vivo measurements and biomarkers. Specific urinary and plasma AGEs N ε -(carboxymethyl)lysine (CML), N ε -(1-carboxyethyl)lysine (CEL), and N δ -(5-hydro-5methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were assessed by mass spectrometry.Results: In 73 individuals (22 males, mean ± SD age and BMI 52 y ± 14, 30.6 kg/m2 ± 4.0), intake of CML, CEL, and MG-H1 differed 2.7, 5.3, and 3.7-fold between the low and high AGE diets, which led 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 (all p for treatment effects > 0.05). Conclusions:This comprehensive RCT demonstrates very limited biological consequences of a 4-week diet low or high in AGEs in abdominally obese individuals.

Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus

“…Stirban et al demonstrated that nutritional AGEs showed direct detrimental effects on the vasculature [ 109 ]. In contrast to Stirban et al’s result, Linkens et al could not find a correlation between high AGE levels and vascular complications [ 110 ].…”

Advanced Glycation End-Products and Their Effects on Gut Health

“…To date, the current literature has questioned many findings from animal and human studies due to the unreliability of the methods used for AGEs measurements. Most studies in the past predominantly measured AGE levels in foods using ELISA [ 61 , 62 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ] instead of ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS), which is currently considered the gold standard for AGE measurements [ 19 , 104 ]. In addition, many studies focused on producing high-AGE and low-AGE diets using high and low baking (heat-treated) methods or changing the cooking technique (boiling, poaching instead of grilling, frying) to adjust the AGE concentrations in foods.…”

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

“…For example, studies in human participants with obesity revealed that one year of oral AGE restriction resulted in reduced insulin resistance compared to individuals consuming a regular AGE diet [14]. In contrast, a recent study reported that 4 weeks of consumption of a high-AGE diet in participants with obesity had no effect on glucose metabolism or vascular function [15]. The basis of these discrepancies may be due to such factors as the differences in the duration of AGE feeding, baseline adiposity, the metabolic state of the studies' participants, and the specific foods and their preparation modes deemed as "high" vs. "regular" or "low"-AGE.…”