The Gut Microbiome in Lean and Overweight Youth With Type 1 Diabetes and Novel Mechanism of Action of Metformin
Overview
- Phase
- Phase 2
- Intervention
- Metformin
- Conditions
- Type 1 Diabetes
- Sponsor
- Heba M. Ismail
- Enrollment
- 114
- Locations
- 1
- Primary Endpoint
- Differences in the gut microbiome in lean and overweight/obese youth with type 1 diabetes
- Status
- Recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
Ovwerweight and obesity prevalence in persons with T1D has increased, which further complicates management and risk for complications. The proposed study is relevant to public health because it helps us understand the role of the gut microbiome in disease pathophysiology in T1D youth with overweight and obesity as well as potential mechanisms to modify disease.
Investigators
Heba M. Ismail
Assistant Professor of Pediatrics
Indiana University School of Medicine
Eligibility Criteria
Inclusion Criteria
- •Overweight/obese youth 11-18 years of age with T1D at time of enrollment.
- •Lean youth 11-18 years of age with T1D at time of enrollment.
Exclusion Criteria
- •Known monogenic forms of diabetes or Type 2 diabetes (confirmed clinically and by genetic/antibody testing).
- •History of ongoing infection or antibiotic treatment within the past month;
- •History of immune-compromise, recurrent infections, steroid intake (inhaled or oral forms) or other immunosuppressant use in the past 6 months.
- •History of chronic gastrointestinal disease and active within the past 6 months, possible or confirmed celiac disease.
- •Participation in any research intervention trials within the past 3 months.
- •History of treatment or use of metformin, a type 2 diabetes medication.
Arms & Interventions
Metformin
This is a group of 30 youth with type 1 diabetes and overweight/obesity who will receive metformin for 6 months.
Intervention: Metformin
Outcomes
Primary Outcomes
Differences in the gut microbiome in lean and overweight/obese youth with type 1 diabetes
Time Frame: Baseline
cross sectional comparison of stool microbiome using metagenomic sequencing data
Differences in the gut microbial metabolites in lean and overweight/obese youth with type 1 diabetes
Time Frame: Baseline
The investigators will measure and compare the stool and serum secondary bile acids using mass spectrometry
Changes in the gut microbiome in overweight/obese youth with type 1 diabetes in response to metformin
Time Frame: Baseline, Month 3, and Month 6
longitudinal comparison before and after taking metformin for 6 months, stool samples will be collected at baseline, 3 months and 6 months and sequenced for microbiome profile using metagenomic sequencing
Changes in the gut microbial metabolites in overweight/obese youth with type 1 in response to metformin
Time Frame: Baseline, Month 3, and Month 6
The investigators will measure and compare the stool and serum metabolites (short chain fatty acids and secondary bile acids) before, during and after 6 months of daily metformin therapy using mass spectrometry
Secondary Outcomes
- Differences in measures of C-peptide as a measure of beta cell health in lean and overweight/obeseT1D youth(Baseline)
- Changes in measures of C-peptide as a measure of beta cell health in overweight/obese T1D youth in response to metformin(Baseline, Month 3, and Month 6)
- Changes in measures of proinsulin as a measure of beta cell health in overweight/obese T1D youth in response to metformin(Baseline, Month 3, and Month 6)
- Differences in measures Proinsulin as a measure of beta cell health in lean and overweight/obeseT1D youth(Baseline)
- Differences in measures of insulin sensitivity in lean and overweight/obese T1D youth(Baseline)
- Changes in measures of insulin sensitivity in overweight/obese T1D youth in response to metformin(Baseline, Month 3, and Month 6)
- Changes in measures of beta cell function using a timed mixed meal tolerance test(Baseline and Month 6)