title: Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial.
abstract: BACKGROUND
  Advanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes.
  
  
  METHODS
  Thirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40-60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks. After a 2-week washout period, study subjects will crossover to receive the alternative dietary treatment for 12 weeks. The primary outcome is the difference in markers of the advanced glycation pathway carboxymethyllysine (CML) and methylglyoxal (MG) between experimental and control treatments. Secondary outcomes include HbA1c, insulin sensitivity, lipid levels, blood pressure, serum glutathione, adiponectin, IL-6, E-selectin, myeloperoxidase, C-reactive protein, Toll-like Receptor 4 (TLR4), soluble receptor for AGE (sRAGE), urinary 8-isoprostanes, faecal bacterial composition and short chain fatty acid profile. Anthropometric measures including BMI and waist circumference will be collected in addition to comprehensive dietary and lifestyle data.
  
  
  CONCLUSIONS
  Prebiotics which selectively stimulate the growth of beneficial bacteria in the human colon might offer protection against AGE-related pathology in people at risk of developing type 2 diabetes.
  
  
  BACKGROUND
  Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000130763.
authors.affiliation: Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria 3004, Australia. nicole.kellow@monash.edu.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Kellow
authors.forename: Melinda T
authors.initials: MT
authors.lastname: Coughlan
authors.forename: Gayle S
authors.initials: GS
authors.lastname: Savige
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reid
mesh_terms: D000328:Adult; D001315:Australia; D015415:Biomarkers / Q000032:analysis; D002985:Clinical Protocols; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000378:metabolism; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018384:Oxidative Stress; D056692:Prebiotics; D011236:Prediabetic State / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D056692:Prebiotics