Role of Methane in Glycemic Control
Nøgleord
Abstrakt
Beskrivelse
Pre-diabetes is defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and affects more than 40% of US adults. While glycemic dysregulation and insulin resistance are central to the progression from pre-diabetes to diabetes, obesity also plays a key role. Research has begun to define the relationship between gut flora, metabolism and weight gain. Animal studies have linked a specific methanogen, Methanobrevibacter smithii, to weight gain, and in humans we have found that increased methane on breath test is associated both with increased body mass index (BMI) and higher blood glucose levels. We also found that methane gas directly slows gut transit by 59% in an in vivo animal model. We hypothesize that this slowing of transit could result in a greater time to harvest nutrients and absorb calories, representing a potential mechanism for elevated post-prandial glycemic excursions and weight gain. In this study, we will test this hypothesis by determining the effects of enteric methane production on glucose excursions, gut transit and energy utilization in obese or overweight, prediabetic, adult subjects.
We will explore the relationship between methane, M. smithii, obesity and gut transit in human subjects using objective measures of metabolic function, glucose excursions, energy utilization and transit studies, to evaluate whether intestinal methane production is associated with a higher incidence of diabetes risk in an obese study population. We will then repeat testing following a course of antibiotics known to eliminate methanogens. This will potentially provide novel therapies for the pre-diabetic patient, and allow new avenues for research.
Datoer
Sidst bekræftet: | 12/31/2018 |
Først indsendt: | 04/29/2012 |
Anslået tilmelding indsendt: | 07/08/2012 |
Først indsendt: | 07/10/2012 |
Sidste opdatering indsendt: | 01/28/2019 |
Sidste opdatering indsendt: | 05/01/2019 |
Dato for første indsendte resultater: | 09/26/2016 |
Dato for første indsendte QC-resultater: | 01/28/2019 |
Dato for første bogførte resultater: | 05/01/2019 |
Faktisk startdato for undersøgelsen: | 03/31/2012 |
Anslået primær afslutningsdato: | 03/31/2014 |
Anslået afslutningsdato for undersøgelsen: | 03/31/2014 |
Tilstand eller sygdom
Intervention / behandling
Drug: Obese/overweight, prediabetic methane positive
Drug: Obese/overweight, prediabetic methane positive
Fase
Armgrupper
Arm | Intervention / behandling |
---|---|
Experimental: Obese/overweight, prediabetic methane positive Neomycin Rifaximin | Drug: Obese/overweight, prediabetic methane positive Neomycin: 500mg po bid for 10 days |
Kriterier for støtteberettigelse
Alder berettiget til undersøgelse | 18 Years Til 18 Years |
Køn, der er berettiget til undersøgelse | All |
Accepterer sunde frivillige | Ja |
Kriterier | Inclusion Criteria: - 18-65 years old with pre-diabetes (hemoglobin a1c of 5.7-6.4%) - BMI > 25.0 - presence of methane on a breath sample (>3ppm) Exclusion Criteria: Subjects will be excluded from the study if they exhibit any of the following: - Diabetes/diabetes medications - Prokinetic medication - Pregnancy - History of bariatric or intestinal surgery (other than cholecystectomy or appendectomy) - Unstable thyroid disease - An active weight loss treatment/plan - Smoking - Dietary restrictions (lactose intolerance, vegan etc) - Other inability to comply with the study procedures, including known allergy to the study antibiotics (neomycin and rifaximin) - Active inflammatory bowel disease (celiac, Crohn's disease, ulcerative colitis) - Antibiotic use in the past month - Subjects who do not have a microwave (for reheating study meals) and a freezer (for storing leftovers and stool samples) will be excluded from this study. - Subjects who have an aspirin sensitivity - Proton pump inhibitor medications or antacids - History of bezoar - Disorders of swallowing - Suspected strictures, fistulas or physiological GI obstruction - GI surgery within 3 months - Severe dysphagia to food or pills - Diverticulitis - Subjects who use an implanted or portable electromechanical device such as a cardiac pacemaker or infusion pump - Subject who have a peanut allergy |
Resultat
Primære resultatforanstaltninger
1. Number of Subjects Who Eradicated Methane on Breath Test [Baseline and 1-14 days following completion of antibiotic treatment]
2. Stool Methanogen Levels [Baseline and 1-60 days following completion of antibiotic treatment]
3. Stool Total Bacteria Levels [Baseline and 1-60 days following completion of antibiotic treatment]
4. Low Density Lipoprotein (LDL) Levels Before and After Antibiotic Therapy [Baseline and 1-60 days following completion of antibiotic treatment]
5. Total Cholesterol Levels Before and After Antibiotic Therapy [Baseline and 1-60 days following completion of antibiotic treatment]
6. Average Daily Caloric Loss in Stool [Baseline and 1-60 days following completion of antibiotic treatment]
7. Gastric Emptying [Baseline and 1-60 days following completion of antibiotic treatment]
Sekundære resultatforanstaltninger
1. Bowel Symptoms - Bloating [Baseline and 1-60 days following completion of antibiotic treatment]
2. Bowel Symptoms - Abdominal Pain [Baseline and 1-60 days following completion of antibiotic treatment]
3. Bowel Symptoms - Constipation [Baseline and 1-60 days following completion of antibiotic treatment]
4. Bowel Symptoms - Diarrhea [Baseline and 1-60 days following completion of antibiotic treatment]
5. Bowel Symptoms - Straining [Baseline and 1-60 days following completion of antibiotic treatment]
6. % Stool Dry Weight [Baseline and 1-60 days following completion of antibiotic treatment]