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 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 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.

TRIAL REGISTRATION: clinicaltrials.gov: NCT03866343, trialregister.nl: NTR7594.

FUNDING: Diabetesfonds and ZonMw.

Original languageEnglish
Article number156950
Number of pages16
JournalJCI INSIGHT
Volume7
Issue number6
Early online date8 Feb 2022
DOIs
Publication statusPublished - 22 Mar 2022

Keywords

  • CARBOXYMETHYL-LYSINE
  • CASE-COHORT
  • DIABETES-MELLITUS
  • ENDOTHELIAL DYSFUNCTION
  • FOLLOW-UP
  • GLYCATION END-PRODUCTS
  • INSULIN-RESISTANCE
  • MICROVASCULAR RECRUITMENT
  • OXIDATIVE STRESS
  • PULSE-WAVE VELOCITY

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