The Gut Microbiome in Type 1 Diabetes and Mechanism of Metformin Action

Phase 2

Recruiting

• Conditions: Type 1 Diabetes; Obesity
• Interventions: Drug: Metformin

• Registration Number: NCT05414409
• Lead Sponsor: Heba M. Ismail

Brief Summary

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 obesity as well as potential mechanisms to modify disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-06-08
• Study First Posted: 2022-06-10
• Study Start: 2022-09-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-08-01
• Study Completion: 2026-11-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

1. Obese youth 11-18 years of age with T1D at time of enrollment.
2. Lean youth 11-18 years of age with T1D at time of enrollment.

Exclusion Criteria

1. Known monogenic forms of diabetes or Type 2 diabetes (confirmed clinically and by genetic/antibody testing).
2. History of ongoing infection or antibiotic treatment within the past month;
3. History of immune-compromise, recurrent infections, steroid intake (inhaled or oral forms) or other immunosuppressant use in the past 6 months.
4. History of chronic gastrointestinal disease, possible or confirmed celiac disease;
5. Participation in any research intervention trials within the past 3 months.
6. History of treatment or use of metformin, a type 2 diabetes medication.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	This is a group of 30 youth with type 1 diabetes and obesity who will receive metformin for 6 months.

Primary Outcome Measures

Name	Time	Method
Changes in the gut microbiome in obese youth with type 1 diabetes in response to metformin	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
Differences in the gut microbiome in lean and obese youth with type 1 diabetes	Baseline	cross sectional comparison of stool microbiome using metagenomic sequencing data
Differences in the gut microbial metabolites in lean and obese youth with type 1 diabetes	Baseline	The investigators will measure and compare the stool and serum secondary bile acids using mass spectrometry
Changes in the gut microbial metabolites in obese youth with type 1 in response to metformin	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 Outcome Measures

Name	Time	Method
Changes in measures of proinsulin as a measure of beta cell health in obese T1D youth in response to metformin	Baseline, Month 3, and Month 6	Serum proinsulin will be used to calculate proinsulin to C-peptide ratio as a measure of beta cell health before and after metformin therapy
Differences in measures of insulin sensitivity in lean and obese T1D youth	Baseline	Insulin sensitivity will be assessed in individuals using the estimated insulin sensitivity score (eIS), which is based on waist circumference (cm), HbA1c (%) and triglycerides (mg/dl)
Changes in measures of C-peptide as a measure of beta cell health in obese T1D youth in response to metformin	Baseline, Month 3, and Month 6	Serum C-peptide will be used to calculate proinsulin to C-peptide ratio as a measure of beta cell health before and after metformin therapy
Changes in measures of insulin sensitivity in obese T1D youth in response to metformin	Baseline, Month 3, and Month 6	Estimated insulin sensitivity score will be used to assess response metformin therapy
Differences in measures Proinsulin as a measure of beta cell health in lean and obese T1D youth	Baseline	The investigators will measure serum proinsulin and calculate a ratio of proinsulin to C-peptide as a marker of beta cell health. These measures will then be compared between the lean and obese T1D youth.
Differences in measures of C-peptide as a measure of beta cell health in lean and obese T1D youth	Baseline	The investigators will measure serum C-peptide to calculate a ratio of proinsulin to C-peptide as a marker of beta cell health. These measures will then be compared between the lean and obese T1D youth.
Changes in measures of beta cell function using a timed mixed meal tolerance test	Baseline and Month 6	Participants in the metformin trial will undergo a standard 2-hour mixed meal tolerance test at baseline and after 6 months of oral metformin therapy

Trial Locations

Locations (1)

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States