# Reversing Diabetic Peripheral Neuropathy Through Exercise

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $733,160

## Abstract

Project Summary
This project proposes an innovative multinuclear MRI approach to gain mechanistic insight into the exercise-
associated adaptations in lower leg muscle function and peripheral nerve integrity of patients with diabetic
peripheral neuropathy (DPN). A significant consequence of DPN is loss of peripheral nerve integrity,
neurogenic muscle atrophy, fatty infiltration, and loss of muscle endurance. These synergistically contribute to
altered gait, impaired balance, and increased fall risk, which can lead to bone fractures, poorly healing wounds,
and chronic infections that often require an amputation. There are no therapies to prevent or reverse the
progress of DPN. Preliminary single-group studies showed that a 10-week moderate-intensity supervised
exercise program is well tolerated by patients with DPN, and improves nerve function, cutaneous innervation,
and cardiovascular and macrovascular endothelial functions. However, the physiological basis of these effects
is poorly defined. Our team is uniquely positioned to use novel multinuclear MRI technology to understand how
exercise affects skeletal muscle and peripheral nerve integrity and function in patients with DPN. We will
prescribe a 10-week exercise program, with both aerobic and strengthening components, to 50 DPN patients
who will receive personal supervision from health professionals. Another 50 DPN patients will be randomly
assigned to the non-exercising control group. We hypothesize that i) exercise will improve peripheral nerve
integrity (fractional anisotropy will increase, and the apparent diffusion coefficient will decrease as measured
using diffusion tensor imaging), ii) exercise will decrease plasma levels of oxidative stress, iii) exercise will
improve DPN symptoms, assessed with the Michigan Neuropathy Screening Instrument. Our second aim is to
determine the effect of exercise on lower leg muscle structure and function in DPN patients. We hypothesize
that i) exercise will increase leg mitochondrial function, as defined by an increase in oxidative capacity
(measured using phosphorus-MRI), ii) exercise will improve leg microvascular function, as defined by an
increase in peak microvascular response (measured using BOLD-MRI), and iii) exercise will decrease
intramuscular fat and increase levels of fat-free muscle (measured using IDEAL-MRI). Advanced multinuclear-
MRI can provide mechanistic insight into exercise-related adaptations in patients with DPN. These include
changes in intramuscular fat content, MV and metabolic functions of the skeletal muscle, as well as peripheral
nerve function and integrity. Understanding these adaptations promises to reveal new ways to improve DPN
symptoms after exercise interventions, better predict patient outcomes, and develop more effective treatments
for DPN.

## Key facts

- **NIH application ID:** 9730470
- **Project number:** 5R01DK114428-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ryan Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $733,160
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9730470

## Citation

> US National Institutes of Health, RePORTER application 9730470, Reversing Diabetic Peripheral Neuropathy Through Exercise (5R01DK114428-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9730470. Licensed CC0.

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