title: Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Monash Centre for Health, Research and Implementation, School of Public Health and Preventive Medicine, and Baker IDI Heart and Diabetes Institute, Melbourne, Australia; barbora.decourten@monash.edu josephine.forbes@mater.uq.edu.au.
authors.forename: Barbora
authors.identifier: http://orcid.org/0000-0001-8760-2511
authors.initials: B
authors.lastname: de Courten
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Maximilian Pj
authors.identifier: http://orcid.org/0000-0001-9997-9359
authors.initials: MP
authors.lastname: de Courten
authors.affiliation: Monash Centre for Health, Research and Implementation, School of Public Health and Preventive Medicine, and Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Georgia
authors.initials: G
authors.lastname: Soldatos
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Dougherty
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Nora
authors.initials: N
authors.lastname: Straznicky
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Markus
authors.initials: M
authors.lastname: Schlaich
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Karly C
authors.initials: KC
authors.lastname: Sourris
authors.affiliation: Monash Centre for Health, Research and Implementation, School of Public Health and Preventive Medicine, and Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Vibhasha
authors.initials: V
authors.lastname: Chand
authors.affiliation: Laboratory for Metabolism and Vascular Medicine, Experimental Internal Medicine, Maastricht University, Maastricht, Netherlands;
authors.forename: Jean Ljm
authors.initials: JL
authors.lastname: Scheijen
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Laboratory for Metabolism and Vascular Medicine, Experimental Internal Medicine, Maastricht University, Maastricht, Netherlands;
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Nutrition and Dietetics, Monash University, Melbourne, Australia; Baker IDI Heart and Diabetes Institute, Melbourne, Australia;
authors.forename: Karen Z
authors.initials: KZ
authors.lastname: Walker
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia; Glycation and Diabetes, Mater Research Institute-University of Queensland, ITranslational Research Institute, Brisbane, Australia; and Mater Clinical School, University of Queensland, Brisbane, Australia barbora.decourten@monash.edu josephine.forbes@mater.uq.edu.au.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004032:Diet; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D006801:Humans; D048289:Imidazolidines / Q000097:blood / Q000652:urine; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000178:diet therapy*; D011765:Pyruvaldehyde / Q000097:blood / Q000652:urine
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D048289:Imidazolidines; D007328:Insulin; C000612723:N(6)-carboxyethyllysine; C048496:N(6)-carboxymethyllysine; D011765:Pyruvaldehyde; D008239:Lysine
keywords: glycotoxin; insulin resistance; insulin secretion; obesity; receptors for AGEs