Insulin Sensitivity Clinical Trial
Official title:
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
The purpose of this study is to determine insulin sensitivity in individuals that are lean normal glucose tolerant subjects after consumption of a normal low fat diet and after a high fat diet and to explore the effects of high fat consumption on the intestinal microbiome, and metabolic endotoxemia.( Aim 1 of the protocol, a separate record is available for Aim 2)
We will test the hypothesis that a high fat diet given to lean, normal glucose tolerant subjects will impair insulin signaling and sensitivity and modify gut microbiome composition and enhance intestinal permeability, which will increase plasma LPS concentration, induce an inflammatory response in peripheral tissues (skeletal muscle). Also we will test the hypothesis that the inflammatory response and insulin resistance caused by high fat ingestion can be ameliorated by administering - a synbiotic (Bifidobacterium longum R0175 and oligofructose) which protects the intestinal epithelial barrier and decreases intestinal translocation of LPS; and - sevelamer, an agent which sequesters lipopolysaccharide (LPS) in the gastrointestinal tract limiting its translocation into the circulation. All subjects are fed both a low fat diet (considered a normal diet) and high fat diet, first one and then the other in no particular sequence. After a washout period participants are fed the other type of high or low fat diet, depending on which diet they were first assigned to in order to compare the effects of the intervention on insulin sensitivity during each diet. ;
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