The effect of the knock down of gut microbiota by antibiotics on parameters of body weight control and insulin sensitivity

Completed

Conditions: adult-onset diabetes
diabetes type 2
obesity
overweight
10018424
10013317

Registration Number: NL-OMON39276

Lead Sponsor: niversiteit Maastricht

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 56

Inclusion Criteria

BMI 25-35 kg/m2, insulin resistant (HOMA_IR > 2.2), caucasian, male, 35-70 years, impaired glucose tolerance (IGT: 2h plasma glucose during 75g OGTT 7.8-11.1 mmol/l) and/or impaired fasting glucose (plasma glucose >= 5.6), stable body weight for at least three months (±3 kg).

Exclusion Criteria

Known allergic reaction to vancomycin, teicoplanine, amoxicillin and other β-lactam antibiotics (penicillins and cefalosporins) or related antibiotics. Diabetes mellitus, hearing disorders, cardiovascular disease, kidney disease, cancer, asthma or bronchitis, liver malfunction, major illness with a life expectancy < 5 years, diseases affecting glucose tolerance (e.g. pheochromocytoma, Cushing*s syndrome, acromegaly), use of antibiotics in the past 3 months, gastrointestinal disease, plans to lose weight and participation in organized sports activities for >3 hours per week.
The use of the following drugs: β-blockers, lipid lowering-drugs (e.g. PPAR γ or PPARa (fibrates) agonists), glucose-lowering agents (including all sulfonylureas, biguanides, a-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin), anti-oxidants or chronic corticosteroids treatment (> 7 consecutive days of treatment).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Before and after treatment, insulin sensitivity (2 step hyperinsulinemic<br /><br>euglycemic clamp) will be investigated (hepatic and peripheral)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary parameters are: fasting and postprandial energy expenditure and<br /><br>substrate metabolism (indirect calorimetry), in vivo fatty acid handling and<br /><br>fatty acid partitioning in skeletal muscle, and gut permeability (multi-sugar<br /><br>test). Furthermore, adipose tissue and skeletal muscle gene/protein expression<br /><br>of markers of oxidative capacity and inflammation will be determined (i.e.<br /><br>AMPK) in addition to inflammatory markers in plasma. Faecal and circulating<br /><br>short- chain fatty acids, and faecal gut microbiota composition (HITChip /NTG<br /><br>sequencing) will be assessed. </p><br>