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. 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.
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. 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.
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
SN - 2379-3708
VL - 7
JO - JCI INSIGHT
JF - JCI INSIGHT
IS - 6
M1 - e156950
ER -