title: The effect of prebiotic supplementation with inulin on cardiometabolic health: Rationale, design, and methods of a controlled feeding efficacy trial in adults at risk of type 2 diabetes.
abstract: Prediabetes is associated with low-grade chronic inflammation that increases the risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). An elevated lipopolysaccharide concentration, associated with dysbiosis of the intestinal microbiota, has been implicated in the development of both T2D and CVD. Selective modulation of the intestinal microbiota with prebiotics reduces intestinal permeability and endotoxin concentrations, inflammation, and metabolic dysfunction in rodents. The effect of prebiotic supplementation on cardio-metabolic function in humans at risk for T2D is not known. The primary aim of this trial is to determine the influence of prebiotic supplementation with inulin on insulin sensitivity and skeletal muscle metabolic flexibility in adults at risk for T2D. We hypothesize that prebiotic supplementation with inulin will improve insulin sensitivity and skeletal muscle metabolic flexibility. We will randomize 48 adults (40-75 yrs) with prediabetes or a score ≥ 5 on the American Diabetes Association (ADA) risk screener to 6 weeks of prebiotic supplementation with inulin (10 g/day) or placebo. Subjects will be provided with all food for the duration of the study, to avoid potential confounding through differences in dietary intake between individuals. Intestinal permeability, serum endotoxin concentrations, insulin sensitivity, skeletal muscle metabolic flexibility, endothelial function, arterial stiffness, and fecal bacterial composition will be measured at baseline and following treatment. The identification of prebiotic supplementation with inulin as an efficacious strategy for reducing cardio-metabolic risk in individuals at risk of T2D could impact clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Mitchell
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Davy
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Halliday
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24060, USA; The Metabolic Phenotyping Core at Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Mathew W
authors.initials: MW
authors.lastname: Hulver
authors.affiliation: The Department of Food Science and Technology, Blacksburg, VA 24060, USA; The Metabolic Phenotyping Core at Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Neilson
authors.affiliation: The Department of Food Science and Technology, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Ponder
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24060, USA; The Metabolic Phenotyping Core at Virginia Tech, Blacksburg, VA 24060, USA; Fralin Translational Obesity Research Center, Virginia Tech, Blacksburg, VA 24060, USA. Electronic address: kdavy@vt.edu.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Davy
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004032:Diet; D019587:Dietary Supplements; D004731:Endotoxins / Q000097:blood; D005243:Feces / Q000382:microbiology; D005260:Female; D065569:Gastrointestinal Absorption / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007444:Inulin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D056692:Prebiotics / Q000008:administration & dosage*; D011236:Prediabetic State / Q000188:drug therapy*; D012107:Research Design; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D004731:Endotoxins; D056692:Prebiotics; D007444:Inulin
keywords: Cardiovascular disease; Diabetes; Diet; Microbiome; Prebiotics