Resistance Training Recommendations for Children and Adolescents With Cystic Fibrosis–Related Diabetes

Abstract

Cystic fibrosis (CF) is the most prevalent hereditary life-threatening disease in the Caucasian population. With the improvement in clinical care, individuals with CF are living longer, and CF-related diabetes (CFRD) has emerged as a major complication. The diagnosis of CFRD is associated with shortening survival, increasing morbidity, worsening physical capacity, and body composition. Engagement in exercise training has become a prominent nonpharmacologic intervention that aims to improve fitness and clinical outcomes in individuals with CF and CFRD. This column will specifically focus on the potential benefits of resistance training and provide recommendations for children and adolescents with CF and CFRD.

INTRODUCTION

Cystic fibrosis (CF) is a multisystem disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel in the epithelium of multiple tissues including lung and pancreas. Mutations in this gene result in shortened lifespan due to pulmonary failure and multisystemic complications. Fortunately, advancements in medical care and the introduction of effective CFTR modulator drugs have improved the life expectancy of this population (33). The most common comorbidity associated with CF is CF-related diabetes (CFRD), which affects up to 40–50% of adults, 19% of adolescents, and 2% of children (19). CF-related diabetes can contribute to morbidity including poor nutrition, pulmonary function decline, and increased pulmonary exacerbations which can begin several years before the diagnosis of diabetes (9,17). When left untreated, CFRD can result in a 3-fold increase in mortality (16).

Although various therapeutic approaches to treat CF exist, the implementation of exercise training has been circulated as a method for improving health-related quality of life, physical work capacity, muscle strength, and respiratory function (36). As an established method for increasing muscular endurance, hypertrophy, strength, and power, resistance training (RT) has been suggested for individuals with CF to improve pulmonary function, inspiratory muscle strength, and exercise tolerance (40). In regard to CFRD, the optimization of glycemic control with insulin has been associated with the reversal of chronic weight loss, prevention of lung disease progression, and improved survival (8,20,22). Growing evidence demonstrates the efficacy of RT to promote overall metabolic health in individuals with type 2 diabetes (T2D) through improvements in glycosylated hemoglobin (HbA1c) and insulin sensitivity, particularly in the early stages of T2D among those with a lower body mass index (11,27,41). Furthermore, RT has the potential for increasing muscle strength and increasing muscle mass which could enhance glycemic control and assist in the prevention of sarcopenia (30). Those with CFRD present unique physiological problems and needs that, although manageable through exercise, require specific and individualized programming. This is even further compounded when targeting early intervention for children and adolescents. Therefore, it is essential to increase awareness about the potential benefits of RT on CF and glucose intolerance or CFRD to continue the substantial progress already made (4).

For the purpose of this article, RT will be defined as “a specialized method of conditioning, which involves the progressive use of a wide range of resistive loads and a variety of training modalities designed to enhance health, fitness, and sports performance” (5). The term “children” will be used to refer to boys and girls between the ages of 7–11 years old, and the term “adolescents” will be used to refer to boys and girls between the ages 12–18 years old (5).

EVIDENCE-BASED EFFECTS OF RESISTANCE TRAINING FOR CYSTIC FIBROSIS

Although CF has been a well-studied problem over the years, there is a lack of randomized controlled trials evaluating the efficacy of RT as a supplement to existing therapeutic approaches; even less examining its effects on CFRD or glucose intolerance. However, the available literature suggests that resistance exercise is beneficial in improving certain cardiopulmonary variables in addition to increases in muscle size and strength (1,14,18,25,31,32,34,37). Specifically, the protocols used in previous studies have resulted in improvements in residual lung volume, forced expiratory volume, forced vital capacity, physical work capacity, and aerobic performance measured through ${\dot{\text{V}}\text{O}}_{\text{2peak}}$ (Table 1). Selvadurai et al. (34) had subjects perform 5 sets of 10 repetitions for both upper and lower-body exercises on a universal weight machine at an intensity of 70% of a maximal subjective resistance. Orenstein et al. (25) focused on upper-body strength training consisting of biceps curls, lat pull-downs, military press, and bench press on a Nordic Power weight resistance machine. More recent studies assigned full-body, circuit-based RT, where subjects performed 1–3 sets of 10–30 repetitions with short rest periods (<60 seconds) at intensities of 30–60% 1 repetition maximum (1 RM) (1,18,31,32). It is suggested that the observed changes can be attributed to increased strength of core muscles involved in respiratory function and increased endurance of the working muscles involved in the specific modality of exercise testing used to assess aerobic fitness. The aforementioned studies have varied in the RT used with some providing vague descriptions of the particular protocol making exercise prescription for optimal results in CFRD or individuals with glucose intolerance difficult. For these reasons, it may be necessary to broaden our scope to provide appropriate RT recommendations for children and adolescents with CFRD and glucose intolerance.

Table 1.

Overview of cystic fibrosis resistance training intervention studies

Author (y)	Intervention						Primary outcomes
	Type	Exercises	Frequency	Volume	Intensity	Duration
Strauss et al. (37) (1987)	Variable weight training using pyramiding technique (high loads, low repetitions)	Squats, dumbbell pullover, incline bench press, flat dumbbell flys, lat pull, seated pulley row, standing barbell curl, and lying triceps extension	—	—	—	6 mo	Increased body mass, upper arm circumference, and strength; decreased RV and RV/TLC
Selvadurai et al. (34) (2002)	Traditional, nonperiodized resistance training	Full body	5 sessions/wk	5 sets of 10 repetitions	70% of maximal subjective resistance	~3 wk	Improved FEV and increased body mass, FFM, and strength
Orenstein et al. (25) (2004)	Number of sets, repetitions, and load lifted were gradually increased per bout	Biceps curls, lat pulldown, military press, and bench press	3 sessions/wk	—	HR kept at <55% of maximum	12 mo	Improved FEV, increased strength, PWC, and body mass, decreased ${\dot{\text{V}}\text{O}}_{\text{2peak}}$
Moorcraft et al. (18) (2004)	Combined aerobic and resistance training	Upper body	3 sessions/wk	Sets of 10–15 repetitions progressed to 20–30	Loads initially 10–15RM then 20–30RM	12 mo	Decrease in lactate and HR following leg ergometer test
Santana-Sosa et al. (32) (2012)	Combined circuit weight and aerobic training	Bench press, shoulder press, leg extension, leg press, leg curl, abdominal crunch, low back extension, arm curl, elbow extension, seated row, and lat pulldown	3 sessions/wk	1 set of 12–15 repetitions	40–60% of 5RM	8 wk	Increased ${\dot{\text{V}}\text{O}}_{\text{2peak}}$ and 5RM
Kriemler et al. (14) (2013)	Traditional, progressive resistance training	Hip abduction, hip adduction, leg extension, leg press, pullover, chest press, torso arm, overhead press, rotatory torso, abdominal flexion, and lower back extension	3 sessions/wk	1 set of 6–9 repetitions	Loads initially 6–9RM	6 mo	Improved FEV
Santana-Sosa et al. (31) (2014)	Combined circuit weight and aerobic training	Leg press, lat pulldown, leg extension, bench press, leg curl, seated row, and abdominal crunch	3 sessions/wk	1 set of 12–15 repetitions	40–50% of 5RM	8 wk	Increased inspiratory muscle strength, ${\dot{\text{V}}\text{O}}_{\text{2peak}}$, 5RM, FFM, and decreased %fat
Beaudoin et al. (1) (2017)	Combined aerobic and resistance training	Full body	3 sessions/wk	1–2 sets of 8–12 repetitions, then 3 sets of 12–15 repetitions	30–50% of 1RM	12 wk	Decreased total glucose excursion

FEV = forced expiratory volume; FFM = fat-free mass; HR = heart rate; PWC = physical work capacity; RM = repetition maximum; RV = residual volume; TLC = total lung capacity; ${\dot{\text{V}}\text{O}}_{\text{2peak}}$ = peak oxygen uptake; %fat = body fat percentage.

RESISTANCE EXERCISE FOR CHILDREN AND ADOLESCENTS

Children and adolescents who are involved in consistent RT have been shown to significantly increase muscular strength and endurance beyond normal growth and maturation (2). The primary mechanism behind the observed strength improvements are believed to be increased neuromuscular function (26,28). These neural adaptations seem to consist of increased motor unit activation, rate of force development, and decreased electromechanical delay, all of which lead to the enhancement of muscle force output. In addition, the displayed neural benefits of resistance exercise seem to compliment the natural proliferation and adaptations observed with puberty among adolescents (24). Although large changes in body composition are typically because of growth, there is evidence demonstrating significantly higher bone mineral density and muscle hypertrophy in adolescents participating in resistance exercise (2,21).

A position statement from the National Strength and Conditioning Association (NSCA) advocates the safety and significant benefits of supervised youth participation in RT (5). The NSCA recommends performing 1–3 sets of 6–15 repetitions through a variety of upper-body and lower-body exercises on 2–3 nonconsecutive days. For power exercises, repetition range should be reduced to 3–6 per set (5). According to the American College of Sports Medicine (ACSM), children and adolescents should participate in ≥3 days per week of various muscle strengthening physical activities, unstructured (e.g., playing on playground equipment), or structured (e.g., lifting weights or working with resistance bands), lasting ≥60 minutes. Structured weightlifting should consist of 8–15 submaximal repetitions inducing moderate fatigue but allowing for good mechanical form (29). The American Academy of Pediatrics recommends RT programs of 2–3 sessions on nonconsecutive days with whole-body workouts lasting 20–30 minutes, consisting of 2–3 sets of 8–15 repetitions (18). To minimize risk of injury, all sessions should be supervised and include adequate warm-ups and cool-downs approximately 10–15 minutes in duration (18). In a position stand from the Canadian Society for Exercise Physiology, RT programs should include 8–12 upper, lower, and core-specific exercises initially starting at 1–2 sets of 8–15 repetitions with “light” to “moderate” loads of 30–60% 1-RM. Gradual progression can be made to 3 sets with heavier loads (e.g., 6–10 RM) performed to volitional fatigue to maximize strength gains (2). Progression should be primarily dictated by health goals and the individual’s exercise skill competency and accumulated time of formal training (38). Although the typically recommended interset rest interval length is 2–3 minutes for adult lifters, younger populations have displayed greater fatigue resistance so shorter durations of ~1 minute may be used for healthy children and adolescents (6).

RESISTANCE TRAINING FOR PULMONARY FUNCTION

One of primary goals when treating CF is to increase pulmonary function. Although aerobic exercise has traditionally been used to accomplish this, evidence exists demonstrating the efficacy of implementing different modalities of resistance exercise to increase cardiopulmonary measures (10,13,35). Previous studies performed in healthy individuals, both recreationally active and sedentary, have shown that traditional RT focusing on lower repetitions per set at higher intensities (e.g., 80% 1-RM) with longer rest periods (e.g., 90–180 seconds) can increase maximal oxygen consumption (${\dot{\text{V}}\text{O}}_2\text{max}$), time to exhaustion, and maximal work rate during cycle ergometer testing (10,13,35). However, circuit-based RTemphasizing high repetitions per set (e.g., >12) and short rest periods (e.g., ≤30 seconds) seems to be the most effective modality for increasing muscular endurance and aerobic conditioning while also eliciting muscular strength and size benefits (12,23). According to meta-analytic data from healthy adults, the largest effects in ${\dot{\text{V}}\text{O}}_{\text{2}}\text{max}$ were observed in programs including 14–30 sessions lasting at least 20–30 minutes over 6–12 weeks with intensities of 60–90% 1 RM for all exercises (12,23). Although increases in aerobic capacity have been observed in those who are healthy, untrained, or trained individuals, the most consistent improvements seem to occur in sedentary individuals with low baseline fitness levels (${\dot{\text{V}}\text{O}}_{\text{2}}\text{max}\le \text{40}$ mL/kg/min). This information would be favorable for youth with CF who demonstrate low ${\dot{\text{V}}\text{O}}_{\text{2}}\text{max}$ values on average (41.5 ± 8.9 mL/kg/min) (15). Currently, there are no resistance exercise prescription recommendations specifically for individuals with CF. However, ACSM offers RT recommendations for individuals with certain respiratory diseases (e.g., asthma and chronic obstructive pulmonary disease) (29). Those with pulmonary-related disorders should participate in RT 2–3 days per week using a variety of weight machines, free weights, and body weight exercises. For strength improvements, beginners should perform 2–4 sets of 8–12 repetitions for each exercise, beginning with intensities between 60 and 70% of 1-RM then progress to ≥80% with experience. To increase endurance, 2–4 sets of 15–20 repetitions should be performed at intensities of ≤50 1-RM.

RESISTANCE EXERCISE FOR GLYCEMIC CONTROL

The emergence of CFRD is believed to mainly be attributed to impaired insulin secretion and decreased insulin sensitivity (1). Those with CFRD usually experience a prolonged period of prediabetes or glucose intolerance with rapidly declining lung function and body mass. In addition, those with CFRD experience numerous glucose excursions, or large fluctuations in blood sugar levels, that could lead to lung infection, inflammation, and oxidative stress (1). The treatment of diabetes mellitus, particularly T2D, has been heavily researched over the years. With engagement in general physical activity being recommended to aide in the management of T2D, RT has been shown to reduce HbA_1c, improve blood lipid profiles, and enhance glycemic control through increased muscle mass for glucose uptake and enhancement of insulin action (11,41). When working with pre-diabetics or individuals with diagnosed diabetes, it is recommended to begin with 1–3 sets of 10–15 repetitions at “moderate” intensities of 50–69% 1 RM for 8–10 exercises targeting the full body. Gradual progression should then be made to sets of 8–10 repetitions corresponding to “vigorous” intensities of 70–85% 1 RM. A review of the literature found that exercise training programs ≥8 weeks with 2–3 sessions per week lasting 30–60 minutes using progressive RT targeting 5–10 muscle groups seem to provide the greatest benefits. Working sets ranged from 2 to 6 of 6–20 repetitions of each exercise with the average being 2–3 sets of 8–12 repetitions (11,41). One major risk for children and adolescents with CFRD would be the possibility of exercise-induced hypoglycemia, especially among those taking insulin. Blood glucose levels of ≤70 mg/dL is an absolute contraindication for exercise with common symptoms including hunger, sweating, nervousness, dizziness, confusion, anxiety, weakness, and increased pulse. As a precaution in the event of hypoglycemia occurring during a session, practitioners should advise clients to consume 15–20 g of carbohydrates to increase glucose values (7,29).

BARRIERS AND SPECIAL CONSIDERATIONS FOR RESISTANCE TRAINING

Qualified instruction and supervision of RT for youth and beginners of all ages is highly recommended. Most injuries within in this population occur on home equipment with unsafe behavior under no supervision. Settings with proper observation and technique coaching produce lower injury rates than those that occur in sports or general recess play at school (18).

These guidelines are only further compounded when dealing with individuals with CF or CFRD. In addition, standard care practices for CF patients includes the use of ongoing physiotherapy, through airway clearance techniques, that traditionally require frequent in-person visits with physicians, physical therapists, and personal trainers. However, the combination of time constraints and travel distance may make long-term management of CF and CFRD through supervised RT and standard therapy unrealistic. Moreover, the recent coronavirus disease 2019 (COVID-19) outbreak has further decreased the likelihood of face-to-face sessions.

Another barrier practitioners need to consider is equipment availability. Generally, resistance exercise is performed with free weights, specialized machines, medicine balls, and resistance bands typically found in gyms, fitness centers, health clubs, and physical therapy clinics. Because COVID-19 is highly contagious and transmitted by close contact among individuals, public health policies recommend social distancing and limiting time in tight spaces with multiple people. A combination of traveling distance and COVID-19 regulations make the access for clients challenging. Previous research and therapeutic practices have used home-based exercise programs for the management of CF and found success. However, adherence and equipment availability may present a problem in the long-term when considering RT principles, such as progressive overload and variation.

According to the World Health Organization, telemedicine means “healing at a distance” and signifies the use of information and communication technologies to improve a person’s outcomes by increasing access to care and medical information. The use of video-calling software, such as Skype or Zoom, is a relatively novel yet growing avenue for rehabilitation therapists and exercise professionals to overcome distancing issues and engage clients in regular training. In addition, implementation of various smartphone-based and other mobile technologies allow for adequate monitoring of physiological variables (e.g., heart rate, blood pressure, step count, and energy expenditure) during exercise sessions. In regard to equipment availability, children and adolescents new to RT will most likely not require relatively heavy weights. In addition, many of the specialized weight machines found in many gyms are designed for adultsized individuals in mind, which may be unsuitable for younger populations. Increases in strength have been observed using a variety of exercise modalities and the primary objective with children and adolescents is the enhancement of resistance exercise technique and physical literacy (2,6,24). For these reasons, practitioners should see significant improvements through the utilization of body weight movements, resistance bands, and light weight dumbbells during the first phases of training.

PROGRAMMING AND RECOMMENDATIONS

A RT program for children and adolescents with CF, including glucose intolerance or CFRD should be designed based on health goals and tailored toward the experience and comfort of the individual. Table 2 provides a summary of RT recommendations. Simple movements that engage large muscle groups are encouraged to enhance motor skills, balance, and coordination. The inclusion of core-strengthening exercises should be emphasized to improve breathing and decrease the risk of injuries that specifically occur in the lower back for this younger population (2). It is worth noting that previous research has provided evidence that individuals with CF have weaker quadriceps muscles compared with healthy individuals and that increases in strength have positive effects on insulin sensitivity and glucose tolerance (1). In addition, research protocols targeting solely lower-body exercises displayed significant improvements in total exercise duration and maximal work output during aerobic capacity testing. For these reasons, practitioners are recommended to use full-body routines consisting ≥7 exercises targeting all major muscle groups. Also, because frequencies of 2–3 sessions per week are traditionally used, 2 differing full-body routines may be implemented, if applicable, to provide exercise variation and avoid possible staleness or boredom of training monotony (39). According to the previously discussed literature, RT for children and adolescents and individuals with pulmonary or metabolic disorders should begin with higher repetitions per set with “low” to “moderate” intensities and short rest periods (e.g., ≤60 seconds). To maintain progressive overload, alternate the use of load (i.e., 5–10% increment increases) and set additions week-to-week and base decisions for progression on performance improvements, such as completing more repetitions than the assigned range during the final set of an exercise for consecutive sessions. Also, keep in mind that not every exercise needs to be progressed at the same time or rate; in other words, volume and intensity can differ between exercises from session-to-session. As an individual improves in fitness, skill, and experience, lower repetitions per set with heavier loads and longer recovery periods can be prescribed. To avoid fatigue accumulation or reduce the risk of injury, deloads, or active recovery weeks, should be taken on a routine basis. Repetition maximum testing (e.g., 1 RM or 10 RM) for certain exercises to evaluate muscular strength progression and assign relative intensities is valid as long as an adequate warm-up, gradual progression of testing loads, and appropriate supervision and instruction is applied (2,6,24). A sample RT program can be seen in Table 3. It should be reiterated that resistance exercise programming, implementation, and supervision should be performed by experienced strength and conditioning professionals. Physical needs and training progression will differ greatly among individuals of all ages and health statuses with no program allowing for a “one size fits all” approach. Although Table 3 provides sample exercises that use free weights (e.g., dumbbells), it is important to note that a wide range of different exercises can be prescribed and result in substantial improvements in overall fitness especially in youth and/or novice lifters. Various online resources, including the NSCA website, can provide exercise suggestions and demonstrations to help practitioners with their programs.

Table 2.

Resistance training recommendations for cystic fibrosis and cystic fibrosis–related diabetes

Frequency: 2–3 d/wk; full-body routines should be used, and no additional benefit has been observed with ≥4 sessions per week

Duration: Warm-ups/cool-downs should last 10–15 min; lifting sessions should last between 30 and 60 min; entire programs can range from 8 to 20 weeks

Intensity: Initial training phases should use relative loads of 30–60%; as individuals become more experienced transition to higher intensities of 60–80%

Volume: 1–2 sets of 12–20 repetitions should be used for beginners; 3–4 sets of 6–12 repetitions can be used for more experienced individuals with heavier loads

Exercise selection: full-body routines consisting of simple movements activated large muscle groups; with increases in training age incorporate more complex, multijoint movements

Exercise order: begin with gross motor, more complex movements then transition to less fatiguing, isolated exercises

Rest periods: 60–90 s for low to moderate intensities and higher repetition ranges; ≥120 for higher intensities and lower repetition ranges

Table 3.

Sample resistance training program for intermediate level adolescent with cystic fibrosis

Workout A—Monday	Workout B—Session B
Goblet squat	Standing lunges
Chest press	Shoulder press
Romanian deadlift	Single-leg stiff-leg deadlift
Bent-over row	Lateral raises
Overhead triceps extension	Bent-over triceps extension
Standing biceps curl	Seated Hammer curls
Sit-ups	Leg raises
Timeline	Sets	Reps	% 1RM	Rest
Week 1	10RM testing
Week 2	1 set	20–30	30	60–90 s
Week 3	1 set	20–30	35	60–90 s
Week 4	1 set	20–30	40	60–90 s
Week 5	2 sets	20–30	40	60–90 s
Week 6	2 sets	20–30	45	60–90 s
Week 7	Recovery/10RM testing
Week 8	2 sets	12–20	50	90–120 s
Week 9	2 sets	12–20	55	90–120 s
Week 10	3 sets	12–20	55	90–120 s
Week 11	3 sets	12–20	60	90–120 s
Week 12	3 sets	12–20	60	90–120 s
Week 13	Recovery/10RM testing
Week 14	2 sets	6–12	65	≥120 s
Week 15	2 sets	6–12	70	≥120 s
Week 16	3 sets	6–12	70	≥120 s
Week 17	3 sets	6–12	75	≥120 s
Week 18	4 sets	6–12	75	≥120 s
Week 19	4 sets	6–12	80	≥120 s
Week 20	Recovery/10RM testing

RM = repetition maximum.

SUMMARY

In summary, the inclusion of exercise training programs are an integral part of preserving and improving aerobic fitness, physical work capacity, and body composition in those with CF. It is imperative that physicians, physiotherapist, and exercise professionals work toward early intervention among children and adolescents with CF and glucose intolerance or CFRD to further improve life expectancy within this population. Regular participation in resistance exercise is an effective method for eliciting favorable muscular adaptations but has also been shown to improve cardiorespiratory function and glycemic control. A well-designed, safe, and evidence-based RT program can help to enhance and prolong the quality of life for children and adolescents with CFRD.

Biography

Clifton J. Holmes is a postdoctoral research scholar in the Program in Physical Therapy and Center for Human Nutrition at the Washington University School of Medicine in St. Louis.

Andrea Granados is a physician and assistant professor of pediatrics in the Division of Pediatric Endocrinology and Diabetes at Washington University School of Medicine in St. Louis.