Probiotics as a Novel Approach to Modulate Gut Hormone Secretion and Risk Factors of Type 2 Diabetes and Complications

Phase 1

• Conditions: Obesity; Type 2 Diabetes
• Interventions: Dietary Supplement: Lactobacillus reuteri

• Registration Number: NCT01250106
• Lead Sponsor: German Diabetes Center

Brief Summary

The investigators aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion and compare these findings to healthy lean subjects.

Detailed Description

Prediabetes and diabetes are accompanied by insufficient gut hormone release, insulin resistance, insufficient insulin secretory capacity and low grade systemic inflammation. Results of recent animal experiments suggest that ingestion of probiotics not only influences gut microbiota composition and intestinal permeability but also secretion of GLP-2 as well as insulin resistance, components of metabolic syndrome and diabetes development. GLP-2 secretion has been suggested to be a key mediator of probiotic effects mediating decreased intestine permeability through binding to intestinal GLP2 receptor in animal studies. Insulinotropic GLP-1, which is reduced in patients with type 2 diabetes, has also been described to be influenced by gut microbiota composition. We aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion. In a prospective, double-blinded, placebo controlled randomized 10 weeks trial we aim to investigate metabolic and immunological changes related to modified gut microbiota by analysing (1) gut hormone secretion, (2) insulin sensitivity and glucose tolerance, and (3) systemic LPS concentrations and immune status.

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-24
• Study First Submitted QC: 2010-11-29
• Study First Posted: 2010-11-30
• Status Verified: 2011-07
• Last Update Submitted: 2011-07-28
• Last Update Posted: 2011-07-29
• Primary Completion: 2011-12
• Study Completion: 2011-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Obese subjects: age 40 - 65 years, obesity (BMI 30-45 kg/m2), non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks.
• Healthy control subjects: non-obese (BMI 19-25 kg/m2), non-diabetic subjects, matched for age and sex, non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks.

Exclusion Criteria

• pregnancy, cancer, chronic diseases, antibiotic therapy, competitive athletes.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Probiotic capsule	Lactobacillus reuteri	-
placebo capsule	Lactobacillus reuteri	-

Primary Outcome Measures

Name	Time	Method
Insulin resistance	8 weeks

Secondary Outcome Measures

Name	Time	Method
gut hormones (GLP-1, GLP-2, GIP)	8 and 10 weeks
insulin secretion	8 and 10 weeks
measurement of cytokines to define the immune status	8 and 10 weeks	measurement and analysis of proinflammatory cytokines (Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß, Macropahge inflammatory protein (MIP)-1ß) and regulatory cytokines (IL-10, transforming growth factor (TGF)-ß, IL1ra) from peripheral blood samples collected during this trial
body weight	8 and 10 weeks

Trial Locations

Locations (1)

German Diabetes Center; 🇩🇪 Düsseldorf, Duesseldorf, Germany