# The Effect of High Intensity Interval Training and Surgical Weight Loss On Distal Symmetric Polyneuropathy Outcomes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $611,500

## Abstract

Project Summary/abstract
Distal symmetric polyneuropathy (DSP) affects upwards of 15% of Americans over the age of 40. This highly
prevalent condition impairs patient's quality of life, causes pain, and results in falls. Patients with DSP caused
by diabetes are at particular risk for ulcerations and lower extremity amputations. Despite the large population
affected by this disease and the significant morbidity that results, no disease modifying therapies exist to
prevent nerve injury. Neuropathic pain medications can reduce the pain from DSP, but do not prevent nerve
damage. Enhanced glucose control has been proven to prevent DSP in patients with type 1 diabetes, but has
only a small effect on patients with type 2 diabetes. As a result, a critical need exists to develop disease modify
therapies for patients with and at risk for DSP.
We propose two potential disease modifying therapies, namely exercise and/or weight loss. To determine the
impact of exercise on DSP outcomes, we plan to randomize patients to high intensity interval training (HIIT) or
routine exercise counseling. We chose HIIT as our exercise regimen because of data supporting increased
compliance in patients with obesity and diabetes. This innovative intervention also has emerging data to
support improved metabolic outcomes in patients with diabetes. We hypothesize that exercise will have the
largest effect on DSP outcomes because of three previous uncontrolled studies documenting substantial
improvement in intraepidermal nerve fiber density and cutaneous regenerative capacity in those receiving an
exercise regimen with little to no weight loss. By comparison, in an uncontrolled study, we found stable IENFD
after two years of significant medical weight loss. While the natural history of IENFD is to decrease in those
with diabetes and pre-diabetes, improvement in IENFD was not seen despite robust weight loss. We propose
to determine the effect of weight loss on DSP outcomes by studying a bariatric surgery population where 55%
of the patients have surgery once they are approved by the surgery review committee. We will stratify HIIT
randomization 1:1 to those that do and those that do not undergo surgery. This non-randomized design will
allow comparison of the effect of surgery to HIIT without the need for an expensive, randomized surgical
intervention trial. Surgical weight loss may have a more robust effect on DSP outcomes than medical weight
loss because of the magnitude and sustainability of weight loss. We will also be able to investigate the effect of
combining surgical weight loss and HIIT.
The proposed aims have the potential to identify promising exercise and/or weight loss interventions for DSP.
This phase 2 study may lead to a definitive phase 3 trial, which would possibly result in the first disease
modifying therapy for DSP. Given the high prevalence and substantial morbidity associated with DSP, such an
intervention is desperately needed.

## Key facts

- **NIH application ID:** 10159243
- **Project number:** 5R01DK115687-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Brian Christopher Callaghan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $611,500
- **Award type:** 5
- **Project period:** 2018-07-06 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159243

## Citation

> US National Institutes of Health, RePORTER application 10159243, The Effect of High Intensity Interval Training and Surgical Weight Loss On Distal Symmetric Polyneuropathy Outcomes (5R01DK115687-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159243. Licensed CC0.

---

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