# The Gut Microbiome in Lean and Obese Youth with Type 1 Diabetes and Novel Mechanism of Action of Metformin

> **NIH NIH K23** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $183,705

## Abstract

PROJECT ABSTRACT
Evidence suggests that type 1 diabetes (T1D) risk and progression are associated with gut bacterial imbalance.
Gut microbiome differences are also associated with and thought to contribute to obesity. Obesity is increasingly
prevalent among children with T1D. Notably, obese children progress faster to T1D with reduced insulin
sensitivity compared to their lean counterparts. This is problematic because reduced insulin sensitivity is
associated with higher exogenous insulin needs, chronic inflammation as well as higher risk for hypoglycemia,
dyslipidemia and long-term diabetes complications. It is unknown to what extent the gut microbiome plays a role
in obesity in T1D youth and their worse outcomes. Therefore, profiling and comparing the gut microbiome in T1D
youth who are obese compared to their lean counterparts is important since the microbiome is potentially
modifiable. In adolescents with T1D, metformin use, in addition to insulin therapy, has been shown to reduce
total daily insulin doses as well as improve whole-body and peripheral insulin sensitivity in those who were
overweight and obese. More recently, in adults with type 2 diabetes, it has been shown to exert its effect in part,
by inducing changes in the gut microbiome with secondary changes in short chain fatty acid (SCFA) and bile
acid (BA) levels. These changes ultimately affect insulin secretion and sensitivity. However, it is unknown
whether similar effects are seen in T1D youth with obesity. We hypothesize, that children with T1D and
obesity, as compared to their lean counterparts, exhibit differences in their gut microbiome profile and
that metformin adjuvant therapy for 6 months will alter the gut microbiome profile, SCFA production and
composition of the BA pool in obese T1D youth. Our preliminary data supports the presence of differences
in the microbiome in these two groups. The specific objective of the proposed research is to determine
differences in the gut microbiome in T1D youth who are lean versus obese and whether these differences are
modifiable. We, therefore, aim to determine: i) the differences in the gut microbiome, SCFA and BA profile in
T1D youth who are lean versus obese, and ii) the effects of metformin treatment on the gut microbiome, SCFA
and BA profile in T1D youth with obesity. My long-term goal is to identify novel treatments to improve disease
management. For aim 1, we will enroll 84 youth with T1D, 42 obese and 42 lean. They will be matched by age,
sex and race. For aim 2, we will prospectively enroll T1D youth enrolled in aim 1 who are obese in a clinical trial
using metformin. We will analyze stool and serum samples using state-of-the-art markers of microbiome profiling,
metagenomics, and metabolomics. We have developed and identified a clear plan and budget to adequately
enroll and analyze samples collected during the funding period. Therefore, this study will allow me to further
develop my research skills in the area of T1D and the...

## Key facts

- **NIH application ID:** 10525313
- **Project number:** 1K23DK129799-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Hebatullah Ismail
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $183,705
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525313

## Citation

> US National Institutes of Health, RePORTER application 10525313, The Gut Microbiome in Lean and Obese Youth with Type 1 Diabetes and Novel Mechanism of Action of Metformin (1K23DK129799-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10525313. Licensed CC0.

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