TY - JOUR
T1 - A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals
AU - Linkens, Armand M. A.
AU - Houben, Alfons J.
AU - Niessen, Petra M.
AU - Wijckmans, Nicole
AU - de Goei, Erica
AU - Van den Eynde, Mathias D. G.
AU - Scheijen, Jean L. J. M.
AU - Waarenburg, Marjo
AU - Mari, Andrea
AU - Berendschot, Tos T. J. M.
AU - Streese, Lukas
AU - Hanssen, Henner
AU - van Dongen, Martien C. J. M.
AU - van Gool, Christel
AU - Stehouwer, Coen D. A.
AU - Eussen, Simone J. P. M.
AU - Schalkwijk, Casper
PY - 2022/3/22
Y1 - 2022/3/22
N2 - 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.
AB - 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.
KW - CARBOXYMETHYL-LYSINE
KW - CASE-COHORT
KW - DIABETES-MELLITUS
KW - ENDOTHELIAL DYSFUNCTION
KW - FOLLOW-UP
KW - GLYCATION END-PRODUCTS
KW - INSULIN-RESISTANCE
KW - MICROVASCULAR RECRUITMENT
KW - OXIDATIVE STRESS
KW - PULSE-WAVE VELOCITY
U2 - 10.1172/jci.insight.156950
DO - 10.1172/jci.insight.156950
M3 - Article
C2 - 35133989
VL - 7
JO - JCI INSIGHT
JF - JCI INSIGHT
SN - 2379-3708
IS - 6
M1 - 156950
ER -