# Recipient Vascular Health as a Novel Factor to Optimize Islet Cell Transplantation as a Functional Cure for Type 1 Diabetes

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $388,123

## Abstract

PROJECT SUMMARY
Islet cell transplant (ICT) can functionally cure type 1 diabetes (T1D) by restoring insulin-producing β-cells.
However, human donor islets are scarce and many recipients convert back to T1D. While ICT is slowly
improving, few consistent predictors of ICT outcomes, in particular recipient factors, have been identified.
Consequently, there is a critical need to identify modifiable recipient predictors of ICT success. The long-term
goal is to further improve ICT precision medicine. Therefore, the objective of this study is to identify modifiable
recipient baseline factors that predict ICT clinical outcomes, to focus the development of feasible, effective pre-
ICT interventions to enhance success. Our compelling preliminary data found that greater β-cell function up to
one year following first ICT was significantly related to recipient baseline levels of markers of better vascular
health: higher HDL, lower blood pressure, narrower carotid intima-media thickness (all clinically available), and
lower intercellular adhesion molecule-1. These data are the basis for our central hypothesis: favorable recipient
baseline vascular health predicts better ICT outcomes, mediated by enhanced recipient insulin sensitivity and
lower β-cell death. The first Aim will determine the utility of recipient baseline levels of clinically available
vascular markers for predicting outcomes (β-cell function) of each ICT. Existing longitudinal data up to one-
year post-ICT will be analyzed using multivariable techniques from both the University of Illinois at Chicago’s
(UIC) clinical trials (Phase 1/2 and 3; n=30 with 56 total ICTs) as a “discovery cohort”, and the multisite Clinical
Islet Transplant (CIT) trials (-06 and -07; n=72 with 114 total ICTs) as a “replication cohort”. Extensive data are
available on multiple vascular markers and insulin sensitivity. Novel circulating microRNAs reflecting β-cell
death will be measured in archived serum from UIC. The second Aim will determine the prospective
association of recipient baseline endothelial function and arterial compliance with outcomes (β-cell function
and glucose variability) of each ICT. Longitudinal data will be collected up to one-year post-ICT in 20 new UIC
recipients, including direct vascular measures, e.g., flow-mediated dilation, microvascular reactivity, central
pulse wave velocity, as well as insulin sensitivity via dual-tracer oral glucose tolerance test, and microRNA
markers of β-cell death. The study’s innovation reframes T1D’s negative effect on vascular health to identify
T1D recipient vascular parameters that predict ICT’s ability to cure T1D. Our rationale is that identifying the
specific recipient vascular factors that predict ICT success could translate into simple, evidence-based
strategies such as diet, exercise, or medications targeting those vascular factors before ICT to enhance
outcomes. The positive impact would be optimizing the capacity of scarce human islets to prevent re-tra...

## Key facts

- **NIH application ID:** 10241855
- **Project number:** 1R56DK124305-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Kirstie Kay Danielson
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,123
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241855

## Citation

> US National Institutes of Health, RePORTER application 10241855, Recipient Vascular Health as a Novel Factor to Optimize Islet Cell Transplantation as a Functional Cure for Type 1 Diabetes (1R56DK124305-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241855. Licensed CC0.

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