Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial

• Published in: The American journal of clinical nutrition 2016-06, Vol.103 (6), p.1426-1433
• Main Authors: de Courten, Barbora, de Courten, Maximilian Pj, Soldatos, Georgia, Dougherty, Sonia L, Straznicky, Nora, Schlaich, Markus, Sourris, Karly C, Chand, Vibhasha, Scheijen, Jean Ljm, Kingwell, Bronwyn A, Cooper, Mark E, Schalkwijk, Casper G, Walker, Karen Z, Forbes, Josephine M
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - analysis; Cardiovascular disease; Cross-Over Studies; Diabetes; Diet; Double-Blind Method; Female; Glucose Clamp Technique; Glucose Tolerance Test; Glycation End Products, Advanced - administration & dosage; Glycation End Products, Advanced - blood; Glycation End Products, Advanced - urine; Humans; Imidazolidines - blood; Imidazolidines - urine; Insulin; Insulin - blood; Insulin Resistance - physiology; Lysine - analogs & derivatives; Lysine - blood; Lysine - urine; Male; Mass spectrometry; Middle Aged; Obesity; Overweight - diet therapy; Pyruvaldehyde - blood; Pyruvaldehyde - urine; Risk assessment; Rodents
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.115.125427

The consumption of advanced glycation end products (AGEs) has increased because of modern food processing and has been linked to the development of type 2 diabetes in rodents. We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals. We performed a double-blind, randomized, crossover trial of diets in 20 participants [6 women and 14 men; mean ± SD body mass index (in kg/m(2)): 29.8 ± 3.7]. Isoenergetic- and macronutrient-matched diets that were high or low in AGE content were alternately consumed for 2 wk and separated by a 4-wk washout period. At the beginning and end of each dietary period, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance test were performed. Dietary, plasma and urinary AGEs N(€)-(carboxymethyl)lysine (CML), N(€)-(carboxyethyl)lysin (CEL), and methylglyoxal-derived hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry. Participants consumed less CML, CEL, and MG-H1 during the low-AGE dietary period than during the high-AGE period (all P < 0.05), which was confirmed by changes in urinary AGE excretion. There was an overall difference in insulin sensitivity of -2.1 mg · kg(-1) · min(-1) between diets (P = 0.001). Insulin sensitivity increased by 1.3 mg · kg(-1) · min(-1) after the low-AGE diet (P = 0.004), whereas it showed a tendency to decrease by 0.8 mg · kg(-1) · min(-1) after the high-AGE diet (P = 0.086). There was no difference in body weight or insulin secretion between diets (P = NS). A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence, a restriction in dietary AGE content may be an effective strategy to decrease diabetes and cardiovascular disease risks in overweight individuals. This trial was registered at clinicaltrials.gov as NCT00422253.