JCI Insight (Mar 2022)

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

  • Armand M.A. Linkens,
  • Alfons J.H.M. Houben,
  • Petra M. Niessen,
  • Nicole E.G. Wijckmans,
  • Erica E.C. de Goei,
  • Mathias D.G. Van den Eynde,
  • Jean L.J.M. Scheijen,
  • Marjo P.H. van den Waarenburg,
  • Andrea Mari,
  • Tos T.J.M. Berendschot,
  • Lukas Streese,
  • Henner Hanssen,
  • Martien C.J.M. van Dongen,
  • Christel C.J.A.W. van Gool,
  • Coen D.A. Stehouwer,
  • Simone J.M.P. Eussen,
  • Casper G. Schalkwijk

Journal volume & issue
Vol. 7, no. 6

Abstract

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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.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 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.RESULTS In 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).CONCLUSION This comprehensive RCT demonstrates very limited biological consequences of a 4-week diet low or high in AGEs in abdominally obese individuals.TRIAL REGISTRATION Clinicaltrials.gov, NCT03866343; trialregister.nl, NTR7594.FUNDING Diabetesfonds and ZonMw.

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