Obesity, Type 1 Diabetes
Conditions
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.
Interventions
DRUGMetformin
Metformin is an oral medication that improves insulin sensitivity.
Sponsors
Heba M. Ismail
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The investigators will examine the differences in the gut microbiome between lean and overweight/obese youth with type 1 diabetes and then enroll the overweight/obese youth with type 1 diabetes into the clinical trial to receive metformin as an intervention.
Eligibility
Sex/Gender
ALL
Age
11 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Overweight/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 and active within the past 6 months, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in the gut microbiome in lean and overweight/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 overweight/obese youth with type 1 diabetes | Baseline | The investigators will measure and compare the stool and serum short chain fatty acids using mass spectrometry |
| Changes in the gut microbiome in overweight/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 |
| Changes in the gut microbial metabolites in overweight/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
| Measure | Time frame | Description |
|---|---|---|
| Differences in measures of C-peptide as a measure of beta cell health in lean and overweight/obeseT1D 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. |
| Differences in measures Proinsulin as a measure of beta cell health in lean and overweight/obeseT1D 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 insulin sensitivity in lean and overweight/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 overweight/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 proinsulin as a measure of beta cell health in overweight/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 |
| Changes in measures of insulin sensitivity in overweight/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 |
| 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 |
Countries
United States
Contacts
CONTACTHeba M Ismail
CONTACTHI Team
Outcome results
None listed