Abstract
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.
Highlights
In-vivo accumulation of advanced glycation endproducts (AGEs), a heterogeneous group of sugar-modified amino groups within proteins and other macromolecules, may drive the pathophysiology of type 2 diabetes [1,2,3,4,5,6] and its associated vascular dysfunction [7,8,9,10,11]
De Courten et al showed an improvement in insulin sensitivity by 2.1 mg/kg/min after a 2 week low compared to high AGE diet in a well-controlled randomized controlled trial (RCT) with crossover design [29]
It is unlikely that the small difference in fat content between our low and high AGE diets masked a change in insulin sensitivity, as far greater differences were needed in intervention trials to elicit such an effect [41], and we found no difference in insulin sensitivity while adjusting for macronutrient intake
Summary
In-vivo accumulation of advanced glycation endproducts (AGEs), a heterogeneous group of sugar-modified amino groups within proteins and other macromolecules, may drive the pathophysiology of type 2 diabetes [1,2,3,4,5,6] and its associated vascular dysfunction [7,8,9,10,11]. Whether reducing AGE intake improves risk factors for type 2 diabetes and vascular dysfunction remains controversial [19]. Micro- and macrovascular function, important contributors to insulin sensitivity [31], beta-cell function [32,33], and cardiovascular risk [34,35,36], have not yet been investigated in a well-controlled RCT. AGEs are widely present in food, but whether restricting AGE intake improves risk factors for type 2 diabetes and vascular dysfunction is controversial. 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
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