Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
Condition: Insulin Sensitivity
MeSH terms: Insulin Resistance
Intervention: Sevelamer; Synbiotic; Maltodextrin; High Fat diet; Low Fat diet
Intervention description: 1.6 g sevelamer + 4.4 g maltodextrin three times a day; 5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.; This is a control group. Maltodextrin, 6 g three times a day; The High Fat diet consists of 60% energy from fat (50% saturated), 15% of energy as carbohydrate and 25% from protein consumed while study intervention is being administered.; The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.
Intervention MeSH terms: Sevelamer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Both genders. All races and ethnic groups.

          -  Premenopausal women in the follicular phase, non-lactating, and with a negative
             pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone
             replacement for ≥6 months.

          -  Hematocrit (HCT)≥ 34%, serum creatinine ≤ 1.4 mg/dl, and normal serum electrolytes,
             urinalysis, and coagulation tests. Liver function tests (LFTs) up to 2 times normal.

          -  Stable body weight (±2%) for ≥ 3 months

          -  Two or less sessions of strenuous exercise/wk for last 6 months.

        Exclusion Criteria:

          -  Presence of diabetes or impaired glucose tolerance based on ADA criteria.

          -  Current treatment with drugs known to affect glucose and lipid homeostasis. If the
             subject has been on a stable dose for the past 3 months, the following agents will be
             permitted: calcium channel blockers, β-blockers, ACE inhibitors, angiotensin receptor
             blockers, and statins

          -  History of allergy to sevelamer.

          -  History of Non-steroidal anti-inflammatory drugs or systemic steroid use for more than
             a week within 3 months.

          -  Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and
             clopidogrel will be permitted if these can be held for seven days prior to the biopsy
             in accordance with the primary physician.

          -  Use of agents that affect gut flora (e.g. antibiotics, colestyramine, lactulose, PEG)
             within 3 months.

          -  History of heart disease (New York Heart Classification greater than grade II; more
             than non-specific ST-T wave changes on the ECG), peripheral vascular disease,
             pulmonary disease, smokers.

          -  Poorly controlled blood pressure (systolic BP>170, diastolic BP>95 mmHg).

          -  Active inflammatory, autoimmune, hepatic, gastrointestinal, malignant, and psychiatric
             disease.

          -  History of gastrointestinal surgery or gastrointestinal obstruction within two years.