# Glucose counterregulation in long standing type 1 diabetes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $401,769

## Abstract

PROJECT SUMMARY
Hypoglycemia contributes substantially to the morbidity and mortality of patients with type 1 diabetes and
advanced type 2 diabetes, and new strategies are needed to restore physiologic defense mechanisms against
the development of severe hypoglycemic episodes. The overall aim of this application is to enhance
understanding of the mechanisms contributing to the recovery of glucose counterregulation and hypoglycemia
symptom recognition in patients with long standing type 1 diabetes and hypoglycemia unawareness through
the investigation of novel cellular and technologic approaches to the amelioration of problematic hypoglycemia.
This application builds on our recent studies demonstrating that intrahepatic islet cell transplantation can
restore both islet cell and sympathoadrenal responses to hypoglycemia and normalize defective glucose
counterregulation. Whether this effect is dependent on sympathetic neural or hormonal (epinephrine) input to
the transplant islets is unknown, and will be investigated in the present proposal to understand its importance
to protection from hypoglycemia, and inform efforts to derive islets from stem cells for transplantation outside of
the liver. In addition, we have shown that implementation of real-time continuous glucose monitoring can
significantly improve the endogenous glucose production response to insulin-induced hypoglycemia, although
this improvement in glucose counterregulation was not observed until 18 months post-intervention. Whether
residual nocturnal hypoglycemia may delay recovery in glucose counterregulation will be examined in the
present proposal implementing overnight hypoglycemia avoidance with use of continuous glucose monitoring
and automated suspension of insulin delivery. Specifically, we will examine 1) whether the recovery of glucose
counterregulation afforded by intrahepatic islet transplantation is dependent on adrenergic input to the islets,
and in the absence of an islet transplant 2) whether more stringent avoidance of hypoglycemia afforded by
automated suspension of insulin delivery can restore glucose counterregulation in patients with long standing
disease, and finally 3) whether clinical metrics of hypoglycemia severity and glycemic lability accurately identify
patients with absent physiologic responses required to defend against the development of low blood glucose.

## Key facts

- **NIH application ID:** 9963243
- **Project number:** 5R01DK091331-10
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael R Rickels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,769
- **Award type:** 5
- **Project period:** 2011-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963243

## Citation

> US National Institutes of Health, RePORTER application 9963243, Glucose counterregulation in long standing type 1 diabetes (5R01DK091331-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9963243. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*