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

Armand Ma Linkens, Alfons Jhm Houben, Petra M Niessen, Nicole Eg Wijckmans, Erica Ec de Goei, Mathias Dg Van den Eynde, Jean Ljm Scheijen, Marjo Ph van den Waarenburg, Andrea Mari, Tos Tjm Berendschot, Lukas Streese, Henner Hanssen, Martien Cjm van Dongen, Christel Cjaw van Gool, Coen DA Stehouwer, Simone Jmp Eussen, Casper G Schalkwijk, Armand Ma Linkens, Alfons Jhm Houben, Petra M Niessen, Nicole Eg Wijckmans, Erica Ec de Goei, Mathias Dg Van den Eynde, Jean Ljm Scheijen, Marjo Ph van den Waarenburg, Andrea Mari, Tos Tjm Berendschot, Lukas Streese, Henner Hanssen, Martien Cjm van Dongen, Christel Cjaw van Gool, Coen DA Stehouwer, Simone Jmp Eussen, Casper G Schalkwijk

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.

Keywords: Clinical Trials; Glucose metabolism; Microcirculation; Vascular Biology.

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists

Figures

Figure 1. Consort flowchart.
Figure 1. Consort flowchart.
Figure 2. Box-and-whisker plots of AGEs in…
Figure 2. Box-and-whisker plots of AGEs in 24-hour urine and plasma before and after a 4-week low- or high-AGE diet in abdominally obese individuals.
(A–J) Black lines indicate median, box edges first and third quartiles, and whiskers indicate minimum and maximum of all data. One participant was deemed noncompliant and was not included in statistical analyses of these variables. This participant is shown as a black dot. Differences within groups after the intervention were assessed by a paired-samples t test, whereas differences between groups after the intervention period were assessed by 1-way ANCOVA with sex, age, and the baseline value of the outcome of interest as a covariate. n = 36 and n = 38 for low- and high-AGE diets, respectively. CEL, Nε-(1-carboxyethyl)lysine; CML, Nε-(carboxymethyl)lysine; MG-H1, Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine; pb, protein-bound.

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