J Pharm Pharm Sci (www.cspsCanada.

org) 22, 22 - 27, 2019

A Review of Beneficial Low-Intensity Exercises in Diabetic Peripheral

Neuropathy Patients
Carley Johnson1 and Jody K. Takemoto1,2
1
Ben and Maytee Fisch College of Pharmacy and 2Department of Pharmaceutical Sciences, Ben and Maytee Fisch College
of Pharmacy, The University of Texas at Tyler

Received, August 27, 2018; Revised, December 11, 2018; Accepted, December 27, 2018; Published, December 27, 2018.

ABSTRACT - The American Diabetic Association standards of medical care for diabetic patients recommends
moderate intensity exercise to help manage diabetes; however, this recommendation may be unmanageable for
patients who have become inactive or unable to reach this intensity. The purpose of this review is to determine if
low-intensity exercises demonstrate improvement in diabetic peripheral neuropathy symptoms in order to utilize
these exercises as a starting point for inactive patients. Studies in low-intensity exercises from 2013 to May 2018
were systematically searched in PubMed, SCOPUS, and Cochrane Library databases. The studies in this research
have shown that low-intensity resistance exercises have promising outcomes such as improvements in pain
interference with daily activities, pain thresholds, and reductions in neuropathy symptoms. Low-intensity aerobic
therapy adds to the quality of life of the patient, and increases in strength of the lower limbs show an improvement
in foot sensation and a reduction in pain and tingling symptoms.
__________________________________________________________________________________________

INTRODUCTION exercises as a starting point for counseling in inactive

patients. Although there are several studies on
Diabetic peripheral neuropathy (DPN) is a treatment modalities used to manage symptoms of
complication of both type 1 and type 2 diabetes [1]. DPN, nonpharmacological approaches such as low-
DPN has a complex pathogenesis marked by both intensity exercises have limited research. This
metabolic and vascular factors [2]. Even though review compares the outcomes of different types of
diabetes is a precursor to neuropathy, hyperglycemia low-intensity exercises studied within the last five
is only one of the many key metabolic events known years.
to cause axonal and microvascular injury [2]. It has
been suggested that damage to small nerve fibers MATERIALS AND METHODS
may precede damage to large nerve fibers which
convey proprioception, innervate skeletal muscles, We systematically searched PubMed, SCOPUS, and
and mediate tendon reflexes [1]. Metabolic Cochrane Library databases for studies on exercise
syndrome and obesity have also been linked to DPN therapy from 2013 to December 2017. We narrowed
[3,4]. In order to better manage diabetes, metabolic the search of “exercise therapy” AND “peripheral
syndrome, and obesity, the recommendation for neuropathy” to a more focused “low-intensity
diabetic patients based on the ADA Guidelines is 150 exercise” AND “peripheral neuropathy” within the
minutes per week of moderate intensity exercise [5]. realm of diabetes. Other searches used to find
For patients who have become inactive or unable to clinical trials and literature reviews include: “aerobic
reach that intensity, this recommendation may be exercise” AND “peripheral neuropathy” and “yoga”
unmanageable. Symptoms that become uncontrolled AND “peripheral neuropathy.” In looking at what to
can lead to a decreased quality of life, increased risk consider low-intensity, we followed the Centers for
of amputaiton, and increased medical costs [6]. Disease Control and the U.S. Department of Health
Therefore, by incoporating low-intensity excerises and Human Services physical activity guidelines
into intial therapy, small increases in both the (Figure 1).
vascular and metabolic pathways could have ___________________________________________________
potential to decrease painful neuropathic symptoms.
Corresponding Author: Jody K. Takemoto, The University of
The purpose of this review is to determine if low- Texas at Tyler, 3900 University Boulevard, Tyler, Texas 75799,
intensity exercises demonstrate improvement in Email: [email protected]
DPN symptoms for pharmacists to utilize these

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 J Pharm Pharm Sci (www.cspsCanada.org) 22, 22 - 27, 2019

Aeorbic
Exercise
Intensity

Relative Absolute
Intensity Intensity

Low
Low
60%-70% HR
Max ≤ 2.9 METs

Moderate
Moderate
70%-80% of HR
Max 3 to 5.9 METs

High High
≥ 80% of HR Max ≥ 6 METs

Figure 1. Categorizing Exercise Intensities. HR Max refers to the maximum heart rate of patient. MET refers to metabolic
equivalent tasks This information is adapted from the Centers for Disease Control, the Office of Disease Prevention and
Health Promotion [7,8].

We looked at these studies to see what benefit, if any, point [8]. Classifying exercises such as walking,
low-intensity weight bearing and non-weight bearing mini-trampoline, and aquatic exercises as aerobic
exercises have on DPN patients. was based on the guidelines (Figure 1) and
determined either by the studies mentioning low-
RESULTS intensity.
There were two studies that showed
As seen in Table 1, a variety of low-intensity improvements with walking. Yoo et al. was a pilot
exercise techniques have been studied in evaluating study looking at exercise in previously inactive
benefits in diabetic neuropathy patients. When diabetic patients (n=14) with peripheral neuropathy
categorizing which exercises are considered aerobic, [9]. This study focused on implementing normal
resistance, balance, or a combination, we followed walking three times a week for 30 minutes
the U.S. Department of Health and Human Services increasingly adding time to 50 minutes over a period
physical activity guidelines [8]. The exercises are of 16 weeks. Participants were between the ages of
categorized by the focus of each study. Aerobic 40 and 70 with diabetes and symptoms of peripheral
exercises are walking, mini-trampoline exercises, neuropathy. Pain was assessed using the Brief Pain
and aquatic therapy. Resistance exercises are those Inventory Short Form for Diabetic Peripheral
completed using additional weights or weight Neuropathy. This scale has a pain intensity
machines with the intention of building muscle. component as well as pain interference assessments
Balance exercises are exercises solely targeted at [9]. Although the data did not suggest a reduction in
improving balance. Combination exercises are pain intensities (p=0.34), the results showed a
compound movements that incorporate multiple statistically significant improvement in pain
exercises such as tai chi and yoga. interference with daily activities such as walking
(p=0.016), sleep (p=0.02), and relationships with
Aerobic exercise others (p=0.006). Additionally, participants
When determining what qualifies as aerobic improved their threshold for intensity of aerobic
exercise, the U.S. Department of Health and Human exercise (p=0.028). In another study, mentioned
Services physical activity guidelines is the starting under the title “resistance exercise” heading below,

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there were also improvements seen with low- technique and Footscan 7 hardware. The two
intensity walking. peripheral neuropathy outcomes were measured
In addition to walking, a low-intensity mini- utilizing the 10-g monofilament test and neuropathy
trampoline exercise was considered. This study was and foot-ulcer-specific quality of life instrument.
a controlled clinical trial comparing patients using Lastly, there was one comparative study of
both weight and non-weight-bearing exercises on a aquatic versus land therapy in low-intensity aerobic
mini-trampoline. Participants in the study was exercise. This was a parallel-group, single-center,
narrowed to a population of 24. Outcome measures single-blind randomized control trial. The
were foot mobility (right foot, p=0.40; left foot, intervention compared the same therapy in water
p=0.012), plantar pressure (right foot, p=0.016; left (n=21) with the same therapy on land (n=19) with
foot, p=0.034), and sensation (p=0.008–0.031) of the measurement outcomes of gait and balance in
feet in diabetic neuropathy patients (n=12) [10]. patients with peripheral neuropathy (n=40) [11]. The
Participants completed trampoline exercises five study showed improvement in gait with aquatic
times a week for a total of an 8-week study (every therapy in comparison to land therapy (control
two weeks the level of difficulty increased). The group); Dynamic Gait Index (p=0.04) and Berg
study found that the mini-trampoline exercises Balance Scale (p=0.86) were the outcome
reduced the risk of foot ulcers while also increasing measurements in water therapy while non-aquatic
muscle strength and balance. The outcomes of this therapy utilized the Berg Balance Scale (p=0.024).
study were measured using range of motion

Table 1. Low-Intensity Exercise Benefits

Exercise Technique Duration Benefit References
Aerobic
Walking 16 weeks  Pain Yoo et al, 2015
12 weeks – Pain intensity Nadi et al, 2017
 Aerobic intensity
 Social Benefits
Mini-Trampoline 8 weeks  Risk of Foot Ulcers Kanchanasamut et al, 2017
 Balance
 Muscle Strength
Aquatic Therapy 4 weeks  Balance / Gait Zivi et al, 2017
Resistance
Weight Machines 12 weeks – Quality of Life Crews et al, 2016
(leg extension, leg press, etc.)  Risk of Foot Ulcers Nadi et al, 2017*
 Muscle Strength
Balance
Swiss Ball 3 weeks  Balance Rojhani-Shirazi et al, 2017
– Knee Reflexes
– Ankle Reflexes
Frenkel Training 3 weeks  Balance Rojhani-Shirazi et al, 2017
Resistance, Flexibility, and Balance
Tai Chi 8 weeks  Balance Alsubiheen et al, 2015
 Heightened Awareness Powell-Cope et al, 2014
10 weeks  Balance Tricks Manor et al, 2013
 Social Benefits
24 weeks  Sensation
 Leg Strength
Yoga 10 months  Balance Muhammad et al, 2014
 Flexibility
Summary of the benefits of exercise as therapy for diabetic neuropathy patients utilizing current studies regarding
exercise, the duration of the study indicates an improvement,  indicates decrease, and – indicates no change. *
indicates the study was combination therapy with vitamin D

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Aquatic therapy showed no change in the Berg Balance Test showed a significant increase in
impairment of everyday activities or quality of life ball training (p<0.01) and Frenkel training (p=0.01).
experienced (p=0.27), and neuropathic pain did not In addition to the Berg Balance Test, other outcomes
improve with land therapy (p=0.46). were measured with the one leg stance test and the
Star Excursion Balance Test.
Resistance exercise
When determining what qualifies as resistance Resistance, flexibility, and balance combination
exercise, the U.S. Department of Health and Human exercise
Services physical activity guidelines was utilized [8]. When determining what qualifies as a combination
Additionally, the only resistance exercise study was exercise, the U.S. Department of Health and Human
in combination with aerobic exercise. The aerobic Services physical activity guidelines is the starting
intensity was evaluated using Figure 1 while the point [8]. These studies have been studied in diabetes
resistance exercises were determined by the within the recent years. These studies define Tai Chi
Michigan Neuropathy Screening Instrument, reflex as having clinical measures of balance,
hammer, and tuning fork. These measurements are musculoskeletal strength and flexibility which also
used to assess distal symmetrical peripheral helped to categorize these exercises in the
neuropathy in diabetes [12]. combination category [15, 16].
The most recent study in resistance exercise is Powell-Cope et al. studied Tai Chi – Yang Style
the combination study of aerobic exercise and (n=17) and Functional Based Training (FBT) (n=19)
resistance training with vitamin D therapy in female interventions in patients [15]. The study compared
patients with diabetic neuropathy (n=90) [13]. This short term (6 weeks) and long term (6 months)
exercise training consisted of 60 minutes of training outcomes of training 1 hour per week. These
3 days a week for 12 weeks. The combined training combination exercise therapies measured qualitative
and vitamin D therapy showed a reduction in tingling improvements in patients’ perceptions of balance
(p=0.001), numbness (p=0.001), pain (p=0.002), and (FBT 6 weeks only), balance tricks, heightened
weakness in the lower limbs (p=0.002) but no awareness of walking (6 weeks only), and social
significant change in knee (p=0.77) or ankle benefits. Similarly, Manor et al. studied the effect of
(p=0.47) reflexes. The outcomes of this study were Tai Chi – Yang Style in patients with peripheral
measured using the pre-post interventions with neuropathy (n=25), eight of which had diabetes [16].
commonly used measures, specifically, the Michigan Foot sole sensation (p=0.003), leg strength –
neuropathy questionnaire, reflex hammer, and tuning measured by knee extensor (p=0.009) and flexor
fork tests. peak torque (p=0.01), and physical function –
measured by six-minute walk test (p<0.001) and
Balance exercise TUG (p<0.001) all improved over a span of 24
The U.S. Department of Health and Human Services weeks. Outcomes were measured using the center-
physical activity guidelines was used to determine of-pressure dynamics, 5.07 gauge Semmes-
what qualified as balance exercise [8]. Rojahani- Weinstein monofilament, Biodex dynamometer, and
Shirazi et al. measured balance in patients with timed up-and-go test.
neuropathy by comparing three arms: a control group
(n=20), ball training group (n=20), and Frenkel DISCUSSION
training group (n=20) [14]. Frenkel exercises were
divided into lying, sitting, and standing positions Low-intensity exercises do show improvements in
each requiring flexion, extension, abduction and diabetic patients experiencing neuropathy [9-18].
adduction exercises [14]. Whereas, ball training The outcomes of each study vary in respect to what
requires the same active movements such as flexion, is being measured. Some studies focused on
extension, abduction and adduction but while alleviating pain or pain interference [9] while others
utilizing the Swiss ball. Exercise training for 55 focused on preventing further complications such as
minutes, 5 days a week for 3 weeks showed falling, ulcers, or amputations [10, 13-18]. Because
significant difference between both exercises in the exercises have different intentions, making a
balance tests. The one leg standing tests observed a comparison to rank which exercise is most beneficial
significant increase from control in both ball training for patients with neuropathy is not possible. Instead,
(p<0.001) and Frenkel (p=0.01) training. Also, the a more appropriate way to apply these studies

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 J Pharm Pharm Sci (www.cspsCanada.org) 22, 22 - 27, 2019

suggest exercises should be tailored to combination of exercise and medication therapies,

subpopulations with diabetic peripheral neuropathy comparisons in length and duration of exercises, and
based on their outcome measurement scales. studies in types of exercises could contribute
Aerobic exercises, alone, at a lower intensity noteworthy evidence for DPN patients striving to
thus far does not show any benefit therapeutically to manage their symptoms. One underlying issue with
the diabetic patient in reference to neither HbA1C each of these studies is the lack of a gold standard in
and blood glucose nor pain intensities [9]; however, measuring outcomes to determine any quantitative or
beginning with a low-intensity exercise improved qualitative improvements; therefore, integrating a
quality of life [9]. More randomized controlled trials system of universal measurements in DPN is
are needed to show benefit. In a patient with too high imperative. This research is novel as this is the first
of a pain intensity to walk on land could experience report to compare low-intensity exercises showing
an improvement in daily activities with aquatic benefits in DPN patients in which pharmacists can
therapy [11]. Additionally, another non-weight use to provide non-pharmacological counseling.
bearing exercise patients could use to see an
improvement in balance is Swiss ball training [14]. ACKNOWLEDGMENTS
Tai-Chi, a combination of resistance, flexibility, and
balance exercises, showed more benefits in both The authors would like to thank Dr. Takova Wallace,
quality of life and peripheral neuropathy symptoms Pharm D, BCPS from the Ben and Maytee Fisch
[15-18]. Also, aerobic exercises in combination with College of Pharmacy at the University of Texas at
resistance training with vitamin D showed Tyler for her advice in developing the foundation of
improvement in peripheral neuropathy symptoms this research.
[13].
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