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.

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 those 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 T2M could impact clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.

糖尿病前期与低度慢性炎症相关，这种炎症会增加患2型糖尿病（T2D）和心血管疾病（CVD）的风险。与肠道微生物群失调相关的脂多糖浓度升高，与2型糖尿病和心血管疾病的发生都有关系。用益生元对肠道微生物群进行选择性调节可降低啮齿动物的肠道通透性和内毒素浓度、炎症以及代谢功能障碍。在有患2型糖尿病风险的人群中，补充益生元对心脏代谢功能的影响尚不清楚。本试验的主要目的是确定补充菊粉益生元对有患2型糖尿病风险的成年人的胰岛素敏感性和骨骼肌代谢灵活性的影响。我们假设补充菊粉益生元将提高胰岛素敏感性和骨骼肌代谢灵活性。我们将把48名患有糖尿病前期或在美国糖尿病协会（ADA）风险筛查中得分≥5的成年人（40 - 75岁）随机分为两组，分别接受为期6周的菊粉益生元补充（10克/天）或安慰剂。在研究期间，将为受试者提供所有食物，以避免因个体间饮食摄入差异而可能产生的混杂因素。将在基线和治疗后测量肠道通透性、血清内毒素浓度、胰岛素敏感性、骨骼肌代谢灵活性、内皮功能、动脉僵硬度以及粪便细菌组成。确定补充菊粉益生元是降低有患2型糖尿病风险个体的心脏代谢风险的有效策略，这可能会通过为饮食建议提供依据以及提高科学界和医学界对益生元的接受度来影响临床实践。