# Modeling Islet Dysfunction During Type 1 Diabetes Progression

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $158,604

## Abstract

PROJECT SUMMARY/ABSTRACT
Over the past 30 years, a number of immunomodulatory agents have been tested in type 1
diabetes (T1D). While a handful of these trials met their primary endpoint, defined as an
improvement in the C-peptide area under the curve response during a mixed meal tolerance
test, no immunomodulatory intervention has yet proven capable of inducing insulin
independence. Furthermore, no drug has been approved as a disease-modifying therapy for
T1D, highlighting an important gap in translating T1D trial results into clinical practice. Here, we
will test the hypothesis that targeted and model-based approaches to document early changes
in β cell function can refine current strategies aimed at preventing loss of insulin secretion in
T1D. We have previously developed and validated a robust mathematical method to model
dynamic parameters of β cell function – including β cell glucose sensitivity, rate sensitivity, and
potentiation – and to estimate insulin sensitivity from standard oral glucose or mixed meal
tolerance tests, known as the Mari/Ferrannini model. Here, we will apply the Mari/Ferrannini
model to existing datasets from completed T1D intervention studies, performed in the Type 1
Diabetes TrialNet and the Immune Tolerance Networks, to define the natural history of β cell
decline in placebo-treated subjects (Aim 1) and determine whether short-term changes in
sensitive model-derived parameters of insulin secretion and insulin clearance can be used to
identify clinical and immunological Responders and Nonresponders at study end (Aim 2). The
successful completion of this work will provide a framework for the design and execution of
shorter trials, help dissect disease and trial heterogeneity, and provide rationale for targeting
interventions to those with the highest prospect of benefit.

## Key facts

- **NIH application ID:** 9959434
- **Project number:** 5R21DK119800-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Carmella Evans-Molina
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,604
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959434

## Citation

> US National Institutes of Health, RePORTER application 9959434, Modeling Islet Dysfunction During Type 1 Diabetes Progression (5R21DK119800-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9959434. Licensed CC0.

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