# Modeling of Insulin and Glucagon Sensitivity During Exercise in Type 1 Diabetes

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $645,525

## Abstract

Project Summary
The objective of this project is to investigate how the glucoregulatory system responds to exercise at different intensities
and for different types of exercise including aerobic and resistance for the purpose of developing a better artificial
pancreas (AP) control system. The experiments proposed here will specifically reveal how exercise impacts 1) non-
insulin mediated glucose uptake, 2) insulin mediated glucose uptake (insulin sensitivity), 3) glucagon responsiveness in
euglycemia, and 4) glucagon responsiveness during hypoglycemia. Exercise commonly results in hypoglycemia in
persons with type 1 diabetes due to a rapid increase in glucose uptake by working muscles as well as an increase in insulin
sensitivity. To date, avoiding exercise-induced hypoglycemia using current closed loop systems has had limited success as
most AP algorithms are designed to react to declines in sensed glucose, and this decline may be significantly delayed from
the onset of exercise. In this project, we propose to evaluate both insulin and glucagon sensitivity during and after exercise
with tracer studies. In the first study, 26 adult subjects with type 1 diabetes will be brought in for three single-tracer,
euglycemic experiments during which exercise will be performed. Subjects will receive intravenous insulin, glucose, and
octreotide (to suppress endogenous hormone production) and will have blood drawn at regular intervals for measurement
of insulin, native glucose, tracer glucose, catecholamine, and fatty acid levels. Glucose control will be managed by an
infusion algorithm developed at OHSU. Subjects will repeat this experiment at three insulin infusion rates, designated
low, medium, and high. Tracer levels will be used to determine rate of appearance (Ra) and rate of disappearance (Rd) of
glucose to assess glucose uptake during exercise. Thirteen subjects will be placed in an arm of moderate aerobic exercise,
and 13 will be placed in an arm of intense aerobic exercise. In the second study, subjects will be brought in for two
consecutive single-tracer experiments, with two arms as outlined above for moderate and intense aerobic exercise. In the
first experiment, subjects will be kept at euglycemia and given three doses of glucagon, one before, one during, and one
after exercise. In the second experiment, glucose infusion rate will be clamped at an initial, basal rate during exercise and
glucagon will be given before, during, and after exercise. Ra and Rd will be calculated and used to determine changes in
glucagon sensitivity during exercise with or without hypoglycemia. Study 1 and 2 will then be repeated for resistance
training rather than aerobic as anaerobic exercise is often associated with less dramatic changes in glucose levels. Data
from these four studies will be used to develop an integrated model of glucose regulation during exercise that can be
integrated in a model predictive control (MPC) algorithm for automated control of insulin ...

## Key facts

- **NIH application ID:** 9895768
- **Project number:** 5R01DK110175-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Joseph El Youssef
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $645,525
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895768

## Citation

> US National Institutes of Health, RePORTER application 9895768, Modeling of Insulin and Glucagon Sensitivity During Exercise in Type 1 Diabetes (5R01DK110175-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895768. Licensed CC0.

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