Exercising with peripheral or autonomic neuropathy: what health care providers and diabetic patients need to know.

The Physician and Sportsmedicine

ISSN: 0091-3847 (Print) 2326-3660 (Online) Journal homepage: http://www.tandfonline.com/loi/ipsm20

Exercising With Peripheral or Autonomic Neuropathy: What Health Care Providers and Diabetic Patients Need to Know Sheri R. Colberg PhD & Aaron I. Vinik MD, PhD To cite this article: Sheri R. Colberg PhD & Aaron I. Vinik MD, PhD (2014) Exercising With Peripheral or Autonomic Neuropathy: What Health Care Providers and Diabetic Patients Need to Know, The Physician and Sportsmedicine, 42:1, 15-23 To link to this article: http://dx.doi.org/10.3810/psm.2014.02.2043

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Date: 17 September 2015, At: 07:39

C L I N I C A L F O C U S : D I A B E T E S , O B E S I T Y, W E I G H T M A N A G E M E N T, AND EXERCISE REGIMEN

Exercising With Peripheral or Autonomic Neuropathy: What Health Care Providers and Diabetic Patients Need to Know

Downloaded by [University of Manitoba Libraries] at 07:39 17 September 2015

DOI: 10.3810/psm.2014.02.2043

Sheri R. Colberg, PhD 1 Aaron I. Vinik, MD, PhD 2 Human Movement Sciences Department, Old Dominion University, Norfolk, VA; 2Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA 1

Abstract: Both peripheral and autonomic neuropathies are characterized by a progressive loss of nerve fiber function. Most peripheral neuropathy affects the extremities, particularly the lower legs and the feet, but also the hands, whereas damage to the autonomic nervous system may lead to imbalances between the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, as well as abnormalities in heart rate control and vascular dynamics. To prescribe or engage in exercise that is both safe and effective, health care providers and patients with diabetes mellitus need to increase their understanding of the pathophysiological nature of neuropathies and the physical activity hurdles that may arise from the presence of a neuropathy. With proper care and preventative measures, patients with diabetes mellitus that experience either type of neuropathy can benefit from regular participation in mild to moderate aerobic, resistance, and balance activities, assuming they take any potential alterations into account to ensure that exercise is safe and effective. Keywords: diabetes; neuropathy; peripheral neuropathy; autonomic neuropathy; exercise; physical activity

Introduction

Correspondence: Sheri R. Colberg, PhD, Human Movement Sciences Department, Old Dominion University, 1006B Student Recreation Center, Norfolk, VA 23529. Tel: 757-683-3356 Fax: 757-683-4270 E-mail: [email protected]

The main manifestations of diabetic neuropathies are peripheral and autonomic in nature and characterized by a progressive loss of nerve fiber function.1–5 Up to 40% of patients with diabetes mellitus (DM) may experience peripheral neuropathy, and 60% of lower extremity amputations are related to suboptimal blood glucose and likely lipid control.6,7 Hyperglycemia causes nerve toxicity, leading to nerve d amage and apoptosis, 8,9 which causes microvascular d amage and p erfusion loss. Peripheral neuropathy affects the body’s extremities, particularly the lower legs and the feet, but also the hands. Neural symptoms resulting from small and large nerve fiber damage can be sensory and/or motor in nature and manifest as neuropathic pain or loss of sensation that, coupled with poor blood flow to affected areas, increases the risk of foot injury, ulceration, and amputation.9,10 Sensations connected to balance and strength can be diminished, and gait can be altered, contributing to the development of orthopedic issues and a greater risk of falling.11,12 The autonomic (central) nervous system innervates the entire human body and is involved in the regulation of every single organ in the body. Before the advent of severe damage to the autonomic nervous system, an imbalance between the sympathetic and parasympathetic nerve fibers which innervate the heart and blood vessels may result in abnormalities in heart rate (HR) control and vascular dynamics that may adversely affect the patient’s ability to exercise.5,13,14

© The Physician and Sportsmedicine, Volume 42, Issue 1, February 2014, ISSN – 0091-3847 15 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.

Sheri R. Colberg and Aaron I.Vinik

Although certain precautions must be taken by patients with these health issues when undergoing physical activity, in most cases exercising is possible and recommended for improving DM management and lowering cardiovascular and amputation risk. To prescribe or engage in exercise that is both safe and effective, health care providers and patients with DM, either type 1 (T1DM) or type 2 (T2DM), need to increase their understanding of the pathophysiological nature of neuropathies and the physical activity hurdles that may arise from their presence.


Materials and Methods

For this review, an extensive literature search was conducted using PubMed. Search terms included combinations of the following related terms: diabetes, type 1 diabetes, type 2 diabetes, exercise, exercise prescription, physical activity, neuropathy, peripheral neuropathy, autonomic neuropathy, cardiac autonomic neuropathy, foot ulcers, and amputations.

Peripheral Neuropathy

Peripheral pain or loss of sensation in the feet or hands is common in patients with T1DM or T2DM.9,15 The most common form, distal symmetrical polyneuropathy, usually involves both small and large nerve fibers and typically becomes symptomatic after many years of chronic, prolonged hyperglycemia in T1DM, whereas adults with T2DM may develop it after only a few years of known poor glycemic control or already have it at or prior to DM diagnosis.2

Benefits of Physical Activity

Mild to moderate exercise may help prevent the onset of peripheral neuropathy.16 Recently, it was found that adults with well-controlled DM engaging in higher levels of moderate to vigorous physical activity were less likely to have peripheral neuropathy than adults who were either active or had good blood glucose control, but not both.17 Although regular physical activity likely cannot fully reverse the symptoms of peripheral neuropathy, older adults with DM and peripheral neuropathy who participated in a 10-week aerobic and strengthening exercise program exhibited significant reductions in pain and neuropathic symptoms and increased intraepidermal nerve fiber branching in a proximal skin biopsy, suggesting that engaging in supervised exercise may be beneficial for patients.18 If nothing else, exercise participation can prevent further loss of muscle strength and flexibility commonly experienced by patients with both small and large nerve fiber damage.2 Of note, a study also 16

demonstrated the effectiveness of 6 months of weekly tai chi training in improving plantar sensation and balance in elderly adults and elderly adults with DM with a large plantar sensation loss,19 and another study has reported that it reduces neuropathic symptoms.20

Symptoms of Peripheral Neuropathy

Symptoms of peripheral neuropathy may be either sensory or motor in nature, depending on the specific small and large nerve fibers affected. Fiber damage frequently manifests as a loss of sensation.21 Alterations in cold, warm, and pain perception and impaired position sense frequently lead to a loss of balance, especially with eyes closed; painless injuries; and foot ulceration, subsequent gangrene, and lower extremity amputations.15,22,23 Other sensory symptoms may include burning, prickling pain, tingling, electric shock–like feelings, aching, tightness, and hypersensitivity to touch.2,24,25 The presence of pain in distal symmetrical polyneuropathy is associated with its clinical severity and the presence of “burning” symptoms, but not with the degree of involvement of large-diameter sensory fibers or DM severity.26 Motor changes may include distal, proximal, or more focal weakness. In upper extremities, distal symptoms may include impaired fine hand coordination and difficulty with tasks (eg, opening jars or turning keys). Early symptoms of foot weakness include foot slapping, toe scuffing, or frequent tripping, whereas proximal limb weakness may result in difficulty ascending and descending stairs, getting up from a seated or supine position, and raising the arms above the shoulders, as well as more frequent falls. Large nerve fiber neuropathy, resulting in loss of sensation in the feet and hands, frequently contributes to ataxia (lack of coordination during gross motor movements), impairing activities of daily living, and causing falls and fractures.2 Motor neuropathy may occur along with sensory neuropathy, resulting in sensorimotor neuropathy.16,25

Alterations in Activities of Daily Living, Balance, and Gait

Poor peripheral nerve function accounts for a portion of worse physical performance in DM and may be directly associated with physical performance in older adults with or without DM.27 Sensations connected to balance and strength can be diminished by peripheral neuropathy, potentially making walking, standing, or getting out of a chair more difficult.28,29 The presence of large-fiber neuropathies even can lead to an impairment in simple activities of daily living, such as buttoning clothing, tying shoelaces, and using the phone.21

© The Physician and Sportsmedicine, Volume 42, Issue 1, February 2014, ISSN – 0091-3847 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.


Exercising With Neuropathy

Older adults are at great risk for falling and fractures due to instability and weakness.30 The critical weakness in the lower limbs related to peripheral neuropathy is impaired dorsiflexion of the big toe, which can lead to snagging the foot on the floor, tripping, and potentially falling. Most falls occur in the home when an elderly person takes the first or last step going up or down a flight of stairs or is rushing to go to the toilet (related to incontinence). These impairments and the risk of falling can be reduced with small changes in exercise, such as using a small rubber ball to do repeated contractions of the hand or using a rubber band as resistance to strengthen dorsiflexion of the foot.21 Educating patients with STEADI (Stopping Elderly Accidents, Deaths, and Injuries) guidelines (http://www.cdc.gov/homeandrecreationalsafety/ Falls/steadi/index.html) may also assist in lowering an older patient’s risk of falls.30 Alterations in gait contribute to the development of orthopedic issues and a greater risk of falling, which may lead elderly patients to become fearful of falling and avoid physical activity.12 Engaging in simple balance and strength training may help alleviate some of these concerns as well. In one study, older adults with T2DM and mild to moderate neuropathy exhibited impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects; however, all these variables as well as their postural dynamics improved after resistance/balance training done thrice-weekly for only 6 weeks.31,32 These results demonstrate that structured exercise has widespread positive effects on physiological function for these individuals, making the use of strength and balance training advisable for older adults at risk for falls, especially for those with peripheral neuropathy.11,33,34 Diabetes mellitus may affect gait mechanics even before the onset of peripheral neuropathy. For instance, patients with T2DM who do not experience overt peripheral neuropathy exhibit altered and less efficient gait patterns that are more apparent during walking at a maximum speed.12 Additionally, walking capacity and performance decrease with the progression of foot complications. Although walking is recommended to improve fitness, it cannot be prescribed to patients without considering the increased risk of plantar injury. Walking exercise may need to be supplemented by partial– or non–weight-bearing exercises to improve physical fitness in patients with DM who have peripheral neuropathy.28

Exercising With Insensate Feet

Decreased sensation associated with peripheral neuropathy carries with it an increased risk of injury, whereas painful

types of neuropathy may increase discomfort during physical activity. Peripheral nerve damage blunts the usual symptoms of pain resulting from high impact on the feet or friction and pressure from footwear, making it easy to develop a blister or sore on the feet without being aware of it and potentially leading to more serious problems without proper prevention and care.35 A simple blister can progress to a full-blown infected abscess or ulcer and ultimately result in gangrene and the need for lower limb amputation if not treated in a timely manner.36 Most DM-related amputations (88%) are preceded by foot ulcers.23 In-shoe peak plantar pressures (PPPs) often are used as a surrogate indicator of injury to the insensitive foot.37 A recent systematic review of 16 studies suggested that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait.38 In one study, when PPP was recorded for the forefoot, midfoot, and heel during level walking and compared to treadmill walking, heel and toe raises, moving from sitting to standing, stair climbing, single leg standing, stationary bicycling, balance ball exercise, and plantar flexion exercise to assess the effects of weightbearing activities, PPP was 13% higher during treadmill walking compared with level walking, but no different when walking speed was used as a covariate. Moreover, mean PPPs were similar or substantially lower for other exercises (with the exception of higher forefoot PPPs with heel raises), suggesting that regular monitoring of insensitive feet may be needed particularly for heel raises and walking at faster speeds.37

Risk of Ulceration (or Reulceration) With Weight-Bearing Activity

Patients without acute foot ulcers can undertake moderate weight-bearing exercise, although anyone with a foot injury, open sore, or ulcer should be restricted to non–weight-bearing and nonaquatic physical activities until the ulceration has fully healed (Table 1). In the past, individuals with insensate feet were advised to avoid weight-bearing activities to reduce the risk of foot ulcerations; however, engaging in weightbearing activity for a year did not lead to foot ulceration in adults with T2DM, suggesting that moderate walking has no effect on the risk of foot ulcers or reulceration as long as all ulcers are healed prior to participation.6,7 In another study, walking on a treadmill, balance exercises, and strengthening exercises for the lower extremities using body-weight resistance were well tolerated by the plantar surfaces of the feet of adults with peripheral neuropathy.39 Thus, weight-bearing




Table 1. Exercise Recommendations for Peripheral Neuropathy • Daily range of motion exercises to help minimize shortening of connective tissue • Patients without acute foot ulcers can engage in mild or moderate weight-bearing exercise, although low-impact activities like cycling, swimming, and aquatic and chair exercise are viable options as well • Patients with a foot injury or open sore should avoid or limit weight-bearing activities because of an increased chance of soft tissue and joint injury • All individuals, particularly those with insensate feet, should engage in balance training exercises, combined with some lower body and core strength training, to lower falls risk • Chair exercises for individuals with limited mobility can improve flexibility and strength • Patients should wear proper footwear and inspect their feet after physical activity to prevent blisters and detect injuries • Avoid jogging because it places a threefold increase in pressure on the foot compared with walking Modified from Exercise and Diabetes: A Clinician’s Guide to Prescribing Physical Activity. Copyright 2013 American Diabetes Association. Reprinted by permission of the American Diabetes Association.

activity can safely be considered following adequate assessment of patients with peripheral neuropathy.7

Daily Foot Care and Footwear

To prevent problems, patients should be educated about proper foot care and the need for frequent foot examinations to prevent ulceration or to catch it early. Daily inspection of feet and use of proper footwear are recommended for prevention and early detection of sores or ulcers.40 All patients should closely examine their feet or enlist someone else to inspect them on a daily basis to detect sores or ulcers early. Foot inspections may need to be done with the assistance of a mirror placed on the floor to see the bottom of the foot to identify redness, discoloration, or swelling.21,41 These recommendations and other safety precautions are given in Table 2. Involving patients in other types of foot monitoring may also be effective in prevention. For example, giving patients monofilaments to take home to test their feet forces them to look at their feet, and this behavioral change has reduced the foot ulceration in our own practice.21,30,42 Similarly, finding areas of local warmth on the feet manually by palpation may detect developing problem areas. Infrared temperature home monitoring of feet has also been tested as an early warning sign to detect problems areas, and it appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.41 Patients should follow recommendations for the use of proper footwear and appropriate socks, and recommendations to use silica gel or air midsoles in their shoes, along with 18

Table 2. Additional Physical Activity Considerations With Peripheral Neuropathy Safety concerns

Actions

Discomfort or pain with physical activity

• Limit weight-bearing options based on level of tolerance • Engage in more non–weight-bearing activities • Monitor feet daily for blisters, cuts, scrapes • Use proper hygiene for foot and skin care • Choose appropriate footwear (shoes and socks) • Consider the need for orthotics or orthopedic shoes • Check the stump every day for redness, blisters, soreness, or swelling (and treat promptly) • Clean the inside of the stump socket daily and dry it well before replacing it on the stump

Foot injury, infection, or ulceration

Use of a prosthetic device (post–lower limb amputation)

From Exercise and Diabetes: A Clinician’s Guide to Prescribing Physical Activity. Copyright 2013 American Diabetes Association. Reprinted by permission of the American Diabetes Association.

polyester or polyester-blend (cotton-polyester) socks to prevent the formation of blisters and to keep their feet dry.43 Furthermore, to promote effective ulcer healing, plantar pressures can be reduced with casts, walkers, and therapeutic footwear.44,45 Patients with neuropathy and foot deformity may need custom footwear, in particular after healing of ulcers has occurred, to redistribute and reduce plantar foot pressures and to prevent reulceration.44–46 During office visits, a simple (but critical) preventative measure for all health care providers is to look in the patients’ shoes before recommending exercise to seek out and eliminate foreign bodies that may be lodged there without detection (due to insensate feet).

Prosthesis Use After Amputation

Younger patients may progress more quickly in gait training and walking than older patients when using a prosthetic limb after amputation.47 Mobility rates 1 year after prosthesis use begins to worsen with increasing age at amputation and a higher level of lower limb amputation.47 In above-knee amputees, good stump quality is critical to enhanced mobility. Incorrect positioning of the stump, which is responsible for hip flexor retraction, should be avoided after surgery.48 In general, sports participation is associated with a beneficial effect on the cardiopulmonary system, psychological well-being, social reintegration, and physical functioning in amputees.49 Regardless of their amputation level, patients with limb amputations can participate in a wide range of



recreational activities. Sports participation should be included in rehabilitation programs, and patients with limb amputations should be encouraged to pursue a physically active life.49 However, proper stump care is critical to continuing physical activity and preventing additional problems related to possible stump skin infection or debridement.48


Autonomic Neuropathy

Autonomic neuropathy remains underrecognized as a complication of DM, although it affects multiple organ systems and can result in orthostatic hypotension, exercise intolerance, gastroparesis, diarrhea, constipation, and urinary incontinence.5,14 Defined by abnormalities of the parasympathetic (PNS) and sympathetic nervous systems (SNS), vagal (PNS) dysfunction usually occurs earlier, although dysfunction of both can be present. Although some degree of autonomic dysfunction is evident in most patients with peripheral nerve damage, stand-alone autonomic neuropathy due to DM is rare.

Cardiac Autonomic Neuropathy

When neuropathy affects the innervation of the heart, it is referred to as cardiac autonomic neuropathy (CAN).50,51 Although only a quarter of patients with DM have CAN, most patients exhibit some alterations in autonomic function, and incidence increases as high as 65% with advancing age and DM duration.52 The presence of CAN doubles mortality risk and results in a greater frequency of silent myocardial ischemia, orthostatic (postural) hypotension, exercise intolerance, and resting tachycardia.3,53–56 Postexercise heart rate recovery provides an accurate diagnostic test for CAN in T2DM.57 Diabetic adults with even minimal evidence of CAN exhibit enhanced SNS excitation, diminished PNS reactivation, and delay in heart rate recovery early in the postexercise recovery period.58 The presence of CAN impairs exercise tolerance and lowers maximal HR.3 It also increases the risk of sudden cardiac death that is at least partly explained by the presence of CAN, leading to reductions in HR recovery and variability. Slower HR recovery after exercise is associated with greater mortality risk.59 Reduced postexercise HR variability in adults with T2DM who experience an exaggerated exercise blood pressure response suggests impairments in vagal modulation.60

Benefits of Physical Activity

Autonomic dysfunction can affect daily activities of patients with DM, particularly related to silent ischemia during exercise, hyperthermia, or light-headedness with standing

and activities. However, moderate-intensity aerobic training can improve autonomic function and reset the balance between SNS and PNS function in patients with and without CAN.51,61,62 In fact, regular exercise training increases HR variability, suggesting a shift in the cardiac sympathovagal balance in favor of PNS dominance in patients with DM. Long-term physical training, therefore, may be an effective means to reverse autonomic dysfunction.61,62 Improvements, however, may only be evident following acute submaximal exercise.63

Exercising With Autonomic Neuropathy

When autonomic dysfunction in any form is present in patients, a conservative approach to exercise is recommended (Table 3). Although most aerobic and resistance activities are suitable, patients may need to avoid rapid changes in movement that may result in fainting and should engage in longer warm-up and cool-down periods, especially for more intense resistance or aerobic training. If postural hypotension is present, inadequate HR and blood pressure responses may occur with incremental work; therefore, these patients should focus on lower intensity activities in which mild changes in both HR and blood pressure are more easily tolerated and lessen ventricular ectopy.64 Increases in physical activity levels must be approached with caution because of the role of the autonomic nervous system in cardiovascular and hormonal regulation during exercise.5,65 Patients with CAN are advised to monitor exercise intensity by means other than HR alone because HR may no longer rise as much as expected or be the best way to monitor intensity unless maximal HR is accurately Table 3. Exercise Recommendations for Autonomic Neuropathy • Patients with autonomic neuropathy (particularly CAN) should avoid high-intensity physical activities unless they have been cleared by a physician to participate • They should also avoid physical exertion in hot or cold environments since dehydration may be a risk for those who have difficulty with thermoregulation • Patients must be made aware that hypotension may occur after vigorous activities • Recumbent cycling or water aerobics may be safer activities for patients with orthostatic hypotension • For better accuracy, patients should monitor exercise intensity using the heart rate reserve method using a measured maximal heart rate, if possible, or use perceived exertion • If gastroparesis is an issue, individuals should carefully plan out when to undertake physical activity (to avoid potential hypoglycemia during exercise done after meals) From Exercise and Diabetes: A Clinician’s Guide to Prescribing Physical Activity. Copyright 2013 American Diabetes Association. Reprinted by permission of the American Diabetes Association.



determined.66 Intensity may be accurately prescribed using the HR reserve method (a percentage of the difference between maximal and resting HR, added to the resting value) during submaximal exercise with maximal HR directly measured, rather than estimated, for better accuracy.51,66 In addition, perceived (subjective) exertion ratings may be used.66 Physical stamina required to engage in longer duration activities may be compromised, and duration should progress slowly.


Exercising With Cardiac Symptoms

When CAN is present, HR responses may be abnormal at rest, during standing, and during breath holding (Valsalva maneuver).66 Cardiac autonomic neuropathy may cause an elevated HR at rest (eg, 100 beats per minute instead of the normal 72), as well as a smaller rise in HR during physical exertion.67 In addition, blood pressure responses may be altered when changing positions or performing isometric exercise. Given the likelihood of silent ischemia, resting and exercise HR alterations, and blood pressure abnormalities, patients with CAN should have physician approval and possibly undergo stress testing to screen for cardiovascular abnormalities before commencing exercise.51 In spite of these possible consequences, physical activity can be undertaken safely when appropriate caution is used (Table 4).

Exercising With Orthostatic Hypotension

Positional change from lying to standing normally results in activation of a baroreceptor-initiated, centrally mediated sympathetic reflex, one that increases peripheral vascular

resistance and accelerates HR. Orthostatic hypotension is characterized by a defect in this reflex arc, resulting in weakness, faintness, dizziness, visual impairment, and syncope due to a blunted catecholamine response to standing and failure of lower limb vascular resistance to increase adequately.64,68,69 Patients with orthostatic hypotension may experience more erratic blood pressure and HR responses to physical activity and should monitor both their blood pressure and their HR during physical activity to determine how different postures (eg, sitting, standing, reclining, supine) affect their symptoms and ability to exercise.70 Severe autonomic neuropathy may make it difficult for an individual to change body positions without experiencing dizziness or fainting.51,67 Dehydration may exacerbate these symptoms, particularly with sweating and fluid losses during exercise, so ensuring adequate hydration is critical. Other causes of occasional dizziness or light-headedness may be relatively minor, including hypoglycemia or prolonged hot tub or sun exposure, and not necessarily indicative of orthostatic hypotension. Even in patients with DM, such symptoms may be caused by dehydration secondary to hyperglycemia and excessive urination. Advanced age, use of certain medications (eg, diuretics and β-blockers), heat exposure, bed rest, and pregnancy are other possible causes.71

Exercising in the Heat

Autonomic neuropathy may increase the risk of impaired thermoregulation during activities in environmental extremes and exercise-related dehydration. The presence of T1DM alone does not alter thermoregulation in the absence of

Table 4. Additional Physical Activity Considerations With Autonomic Neuropathy Safety Concerns

Actions

Altered ability to recognize signs and symptoms of hypoglycemia

• • • • • • • • • • • •

Blunted heart rate responses to physical activity Erratic blood pressure and heart rate response during exercise, along with increased risk of postural hypotension

Lack of effective thermoregulation for hot and cold environments

Erratic emptying rate of stomach and digestion of food

Discomfort following consumption of a meal or specific type of food

Monitor blood glucose during physical activity Set higher blood glucose goals Monitor intensity with perceived exertion, heart rate reserve, or “talk” test Monitor blood pressure during physical activity Monitor heart rate responses during exercise Determine if different positions (sitting, standing, reclining, supine) affect results Ensure adequate hydration Monitor environment Drink fluids to prevent dehydration Wear proper clothing Monitor blood glucose as needed Use foods partially absorbed in the mouth to treat hypoglycemia (eg, glucose tabs, glucose gels, and hard candies) • Delay injection of rapid-acting insulin until after activity • Determine if physical activity impedes or promotes food mobility • Plan timing of physical activity as symptoms tolerate

Modified from Exercise and Diabetes: A Clinician’s Guide to Prescribing Physical Activity. Copyright 2013 American Diabetes Association. Reprinted by permission of the American Diabetes Association.

20




autonomic dysfunction; during light- to moderate-intensity exercise performed under conditions permitting full sweat evaporation, otherwise healthy T1DM patients do not exhibit impaired heat loss responses during heat exposure.72 Conversely, older adults with T2DM have been shown to have a reduced capacity to dissipate heat during exercise, resulting in greater heat storage and higher thermal strain.73 Heat dissipation is more problematic in patients with autonomic neuropathy because sweating is reduced in the periphery and can occur only in the upper body, easily resulting in overheating. For older patients with T2DM or those with autonomic damage, extra fluids may need to be consumed to protect against both dehydration and hyperthermia, and exercise may need to be avoided or reduced in hotter climates or during warmer parts of the day.74

Exercising With Gastroparesis

Gastroparesis resulting from autonomic nerve damage results in a lessened ability to digest and absorb carbohydrates and food and delays gastric emptying, which may increase the incidence and severity of hypoglycemia.75 It affects approximately 40% of patients with T1DM and up to 30% of patients with T2DM,75 typically causing nausea, vomiting, early satiety, bloating, postprandial fullness, intestinal pain, alternating bouts of constipation and diarrhea, and lack of appetite. The presence of any of these symptoms can make physical activity more difficult to perform because medications and foods must be regulated prior to and during exercise to minimize their impact.76 Eating large meals before exercise should be avoided, as doing so could result in delayed emptying of food; therefore, only small food portions before exercise are recommended. Patients should use rapidly absorbed glucose tablets to treat hypoglycemia and whenever blood glucose levels decrease to 100 mg/dL to prevent severe hyperglycemia.

Exercising With Altered Hormonal Responses

In patients with T1DM, autonomic neuropathy further reduces counterregulatory catecholamine responses, which increases the risk of severe hypoglycemia associated with exercise.77 However, intensive therapy with an emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in patients with autonomic dysfunction despite marginal improvement in adrenaline responses; prevention of hypoglycemia also results in a lower occurrence despite impaired counterregulation.78 Thus, autonomic neuropathy, long DM duration, and antecedent recent hypoglycemia contribute,

to different extents, to impaired adrenaline responses and hypoglycemia unawareness (which is largely a reversible condition with prevention of hypoglycemia).79 In adults with T2DM, autonomic neuropathy is associated with cognitive decline, which may lead to less effective self-management of blood glucose levels.80 Moreover, mild cognitive decline is not uncommon in adults with T1DM.81 Due to the risk of hypoglycemic mortality, typically from cardiac arrhythmias, glycemic goals in DM should be individualized and based in part on the risk of hypoglycemia.65,82 Thus, the risk of hypoglycemia and level of responsiveness are crucial to consider when proposing an exercise program to patients with either type of DM.

Conclusion

The development of peripheral nerve damage is common in patients with T1DM or T2DM and increases the risk of developing an ulcer and undergoing a lower limb amputation. Additionally, many patients with DM develop autonomic nerve dysfunction, which can potentially affect the ability to exercise and engage in normal activities of daily living and alter normal exercise responses (such as HR and blood pressure). To prescribe or undertake exercise that is both safe and effective, health care providers and patients with DM need to increase their understanding of the physiological nature of neuropathies and physical activity hurdles that may arise from their presence. With proper care and preventative measures, patients with DM and either type of neuropathy can benefit from regular participation in mild to moderate aerobic, resistance, and balance activities, assuming they take any potential alterations into account to ensure that exercise is safe and effective.

Conflict of Interest Statement

Sheri R. Colberg, PhD, is on the advisory board/committee of Perrigo Diabetes Care for research in the area of diabetes products. Aaron I. Vinik, MD, PhD, has received funding from Pfizer Inc and Sangamo BioSciences, Inc, for research on neuropathic pain and from Tercica, Inc and Eisai Inc for research on neuroendocrine tumors.

References 1. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26(5):1553–1579. 2. Casellini CM, Vinik AI. Clinical manifestations and current treatment options for diabetic neuropathies. Endocr Pract. 2007;13(5):550–566. 3. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115(3):387–397. 4. Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball for cardiovascular disease? Diabetes Care. 2010;33(7):1688–1690. doi:10.2337/ dc10–0745.



Sheri R. Colberg and Aaron I.Vinik 5. Vinik AI, Erbas T. Diabetic autonomic neuropathy. Handbook of Clinical Neurology. 2013;117:279–294. 6. Lemaster JW, Mueller MJ, Reiber GE, et al. Effect of weight-bearing activity on foot ulcer incidence in people with diabetic peripheral neuropathy: feet first randomized controlled trial. Phys Ther. 2008;88(11):1385–1398. 7. Lemaster JW, Reiber GE, Smith DG, et al. Daily weight-bearing activity does not increase the risk of diabetic foot ulcers. Med Sci Sports Exerc. 2003;35(7):1093–1099. 8. Singleton JR, Smith AG, Russell JW, et al. Microvascular complications of impaired glucose tolerance. Diabetes. 2003;52(12):2867–2873. 9. Smith AG, Singleton JR. Impaired glucose tolerance and neuropathy. Neurologist. 2008;14(1):23–29. 10. Coccheri S. Approaches to prevention of cardiovascular complications and events in diabetes mellitus. Drugs. 2007;67(7):997–1026. 11. Tofthagen C, Visovsky C, Berry DL. Strength and balance training for adults with peripheral neuropathy and high risk of fall: current evidence and implications for future research. Oncol Nursing Forum. 2012;39(5):E416–E424. 12. Ko SU, Stenholm S, Chia CW, et al. Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy—results from the Baltimore Longitudinal Study of Aging. Gait Posture. 2011;34(4):548–552. 13. Vinik A. The question is, my dear Watson, why did the dog not bark?: the Joslin 50-year medalist study. Diabetes Care. 2011;34(4):1060–1063. doi:10.2337/dc11–0146. 14. Vinik AI. The conductor of the autonomic orchestra. Front Endocrinol. 2012;3:71. 15. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132–e173. 16. Balducci S, Iacobellis G, Parisi L, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications. 2006;20(4):216–223. 17. Loprinzi PD, Hager KK, Ramulu PY. Physical activity, glycemic control, and diabetic peripheral neuropathy: a national sample [published online ahead of print September 30, 2013]. J Diabetes Complications. doi:10.1016/j.jdiacomp.2013.08.008. 18. Kluding PM, Pasnoor M, Singh R, et al. The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy. J Diabetes Complications. 2012;26(5):424–429. 19. Richerson S, Rosendale K. Does Tai Chi improve plantar sensory ability? A pilot study. Diabetes Technol Ther. 2007;9(3):276–286. 20. Ahn S, Song R. Effects of Tai Chi exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy. J Altern Complement Med. 2012;18(12):1172–1178. 21. Vinik AI, Ullal J, Parson HK, et al. Diabetic neuropathies: clinical manifestations and current treatment options. Nat Clin Pract Endocrinol Metab. 2006;2(5):269–281. 22. US Department of Health and Human Services Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services Centers for Disease Control and Prevention, 2011. 23. Alvarsson A, Sandgren B, Wendel C, et al. A retrospective analysis of amputation rates in diabetic patients: can lower extremity amputations be further prevented? Cardiovasc Diabetol. 2012;11(1):18. 24. Pittenger GL, Mehrabyan A, Simmons K, et al. Small fiber neuropathy is associated with the metabolic syndrome. Metab Syndr Relat Disord. 2005;3(2):113–121. 25. Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26(3):770–776. 26. Mondelli M, Aretini A, Baldasseroni A. Distal symmetric polyneuropathy in diabetes. Differences between patients with and without neuropathic pain. Exp Clin Endocrinol Diabetes. 2012;120(1):45–50.

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27. Strotmeyer ES, de Rekeneire N, Schwartz AV, et al. The relationship of reduced peripheral nerve function and diabetes with physical performance in older white and black adults: the Health, Aging, and Body Composition (Health ABC) study. Diabetes Care. 2008;31(9): 1767–1772. 28. Kanade RV, van Deursen RW, Harding K, et al. Walking performance in people with diabetic neuropathy: benefits and threats. Diabetologia. 2006;49(8):1747–1754. 29. Miller KL, Magel JR, Hayes JG. The effects of a home-based exercise program on balance confidence, balance performance, and gait in debilitated, ambulatory community-dwelling older adults: a pilot study. J Geriatr Phys Ther. 2010;33(2):85–91. 30. Vinik AI, Strotmeyer ES, Nakave AA, et al. Diabetic neuropathy in older adults. Clin Geriatr Med. 2008;24(3):407–435. 31. Morrison S, Colberg SR, Mariano M, et al. Balance training reduces falls risk in older individuals with type 2 diabetes. Diabetes Care. 2010;33(4):748–750. 32. Morrison S, Colberg SR, Parson HK, et al. Relation between risk of falling and postural sway complexity in diabetes. Gait Posture. 2012;35(4):662–668. 33. Allet L, Armand S, de Bie RA, et al. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010;53(3):458–466. 34. Kruse RL, Lemaster JW, Madsen RW. Fall and balance outcomes after an intervention to promote leg strength, balance, and walking in people with diabetic peripheral neuropathy: “feet first” randomized controlled trial. Phys Ther. 2010;90(11):1568–1579. 35. Abbott CA, Vileikyte L, Williamson S, et al. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care. 1998;21(7):1071–1075. 36. Hunt D. Diabetes: foot ulcers and amputations. Clin Evid (Online). 2011. doi:pii:0602. 37. Shah KM, Mueller MJ. Effect of selected exercises on in-shoe plantar pressures in people with diabetes and peripheral neuropathy. Foot (Edinb). 2012;22(3):130–134. 38. Fernando M, Crowther R, Lazzarini P, et al. Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure [published online ahead of print August 27, 2013]. Clinical Biomechanics (Bristol, Avon). doi:10.1016/j. clinbiomech.2013.08.004. 39. Tuttle LJ, Hastings MK, Mueller MJ. A moderate-intensity weightbearing exercise program for a person with type 2 diabetes and peripheral neuropathy. Phys Ther. 2012;92(1):133–141. 40. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293(2):217–228. 41. Lavery LA, Higgins KR, Lanctot DR, et al. Preventing diabetic foot ulcer recurrence in high-risk patients: use of temperature monitoring as a self-assessment tool. Diabetes Care. 2007;30(1):14–20. 42. Bourcier ME, Ullal J, Parson HK, et al. Diabetic peripheral neuropathy: how reliable is a homemade 1-g monofilament for screening? J Fam Pract. 2006;55(6):505–508. 43. Colberg SR, Sigal RJ, Fernhall B, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33(12): e147–e167. 44. Bus SA. Foot structure and footwear prescription in diabetes mellitus. Diabetes Metab Res Rev. 2008;24(Suppl 1):S90–S95. 45. Bus SA, Valk GD, van Deursen RW, et al. The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic review. Diabetes Metab Res Rev. 2008;24(Suppl 1):S162–S180. 46. Reiber GE, Smith DG, Wallace C, et al. Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial. JAMA. 2002;287(19):2552–2558. 47. Davies B, Datta D. Mobility outcome following unilateral lower limb amputation. Prosthet Orthot Int. 2003;27(3):186–190.



Exercising With Neuropathy 48. Traballesi M, Porcacchia P, Averna T, et al. Prognostic factors in prosthetic rehabilitation of bilateral dysvascular above-knee amputee: is the stump condition an influencing factor? Eura Medicophys. 2007; 43(1):1–6. 49. Bragaru M, Dekker R, Geertzen JH, et al. Amputees and sports: a systematic review. Sports Med. 2011;41(9):721–740. 50. Vinik AI, Erbas T. Cardiovascular autonomic neuropathy: diagnosis and management. Curr Diab Rep. 2006;6(6):424–430. 51. Vinik AI, Maser RE, Ziegler D. Autonomic imbalance: prophet of doom or scope for hope? Diabet Med. 2011;28(6):643–651. 52. Ziegler D, Gries FA, Spuler M, et al. The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J Diabetes Complications. 1992;6(1):49–57. 53. Ciccone MM, Niccoli-Asabella A, Scicchitano P, et al. Cardiovascular risk evaluation and prevalence of silent myocardial ischemia in subjects with asymptomatic carotid artery disease. Vasc Health Risk Manag. 2011;7:129–134. 54. Lievre MM, Moulin P, Thivolet C, et al. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening. Trials. 2011;12:23. 55. Wackers FJ, Young LH, Inzucchi SE, et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care. 2004;27(8):1954–1961. 56. Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management [published online ahead of print June 22, 2011]. Diabetes Metab Res Rev. doi:10.1002/dmrr.1239. 57. Sacre JW, Jellis CL, Coombes JS, et al. Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy. Diabet Med. 2012;29(9):e312–e320. 58. Banthia S, Bergner DW, Chicos AB, et al. Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus. J Diabetes Complications. 2013;27(1):64–69. 59. Turker Y, Aslantas Y, Aydin Y, et al. Heart rate variability and heart rate recovery in patients with type 1 diabetes mellitus. Acta Cardiologica. 2013;68(2):145–150. 60. Weston KS, Sacre JW, Jellis CL, et al. Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus. J Sci Med Sport. 2013;16(1):8–12.61. 61. Loimaala A, Huikuri HV, Koobi T, et al. Exercise training improves bar oreflex sensitivity in type 2 diabetes. Diabetes. 2003;52(7):1837–1842. 62. Pagkalos M, Koutlianos N, Kouidi E, et al. Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy. Br J Sports Med. 2008;42(1):47–54. 63. Figueroa A, Baynard T, Fernhall B, et al. Endurance training improves post-exercise cardiac autonomic modulation in obese women with and without type 2 diabetes. Eur J Appl Physiol. 2007;100(4):437–444. 64. Purewal TS, Watkins PJ. Postural hypotension in diabetic autonomic neuropathy: a review. Diabet Med. 1995;12(3):192–200.

65. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(Suppl 2):1–53. 66. Colberg SR, Swain DP, Vinik AI. Use of heart rate reserve and rating of perceived exertion to prescribe exercise intensity in diabetic autonomic neuropathy. Diabetes Care. 2003;26(4):986–990. 67. Maser RE, Lenhard MJ. Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. J Clin Endocrinol Metab. 2005;90(10):5896–5903. 68. Khoharo HK, Halepoto AW. QTc-interval, heart rate variability and postural hypotension as an indicator of cardiac autonomic neuropathy in type 2 diabetic patients. J Pakistan Med Assoc. 2012;62(4):328–331. 69. Witte DR, Tesfaye S, Chaturvedi N, et al. Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus. Diabetologia. 2005;48(1):164–171. 70. Figueroa JJ, Basford JR, Low PA. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med. 2010;77(5):298–306. 71. Caldwell JE. Diuretic therapy and exercise performance. Sports Med. 1987;4(4):290–304. 72. Stapleton JM, Yardley JE, Boulay P, et al. Whole-body heat loss during exercise in the heat is not impaired in type 1 diabetes. Med Sci Sports Exerc. 2013;45(9):1656–1664. 73. Kenny GP, Stapleton JM, Yardley JE, et al. Older adults with type 2 diabetes store more heat during exercise. Med Sci Sports Exerc. 2013;45(10):1906–1914. 74. Petrofsky J, Berk L, Al-Nakhli H. The influence of autonomic dysfunction associated with aging and type 2 diabetes on daily life activities. Exp Diabetes Res. 2012;2012:657103. 75. Parkman HP, Fass R, Foxx-Orenstein AE. Treatment of patients with diabetic gastroparesis. Gastroenterol Hepatol. 2010;6(6):1–16. 76. Ma J, Rayner CK, Jones KL, et al. Diabetic gastroparesis: diagnosis and management. Drugs. 2009;69(8):971–986. 77. Meyer C, Grossmann R, Mitrakou A, et al. Effects of autonomic neuro pathy on counterregulation and awareness of hypoglycemia in type 1 diabetic patients. Diabetes Care. 1998;21(11):1960–1966. 78. Fanelli C, Pampanelli S, Lalli C, et al. Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation. Diabetes. 1997;46(7):1172–1181. 79. Realsen JM, Chase HP. Recent advances in the prevention of hypoglycemia in type 1 diabetes. Diabetes Technol Ther. 2011;13(12): 1177–1186. 80. Zaslavsky LM, Gross JL, Chaves ML, et al. Memory dysfunction and autonomic neuropathy in non-insulin-dependent (type 2) diabetic patients. Diabetes Res Clin Pract. 1995;30(2):101–110. 81. Ryan CM, Geckle MO, Orchard TJ. Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications. Diabetologia. 2003;46(7):940–948. 82. Cryer PE. Hypoglycemia-associated autonomic failure in diabetes. Handbook of Clinical Neurology. 2013;117:295–307.


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