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Chapter 5 Aerobic Exercise Rx for Type 2 Diabetes

Although physical activity is a key element in type 2 diabetes (T2D) management, many people with this chronic disease do not become or remain regularly active (Morrato 2007). Many high-quality studies done to date have established that participation in regular physical activity improves blood glucose control, blood lipids, blood pressure, cardiovascular risk, mortality risk, and quality of life. Acute and chronic improvements in insulin action with aerobic exercise training are primarily responsible for the enhanced glycemic control (King 1995; Boulé 2001, 2005; O’Gorman 2006).

The treatment goal for individuals with T2D is to achieve and maintain optimal blood glucose, lipid, and blood pressure levels to prevent or delay chronic complications of diabetes (American Diabetes Association 2013). Many people with T2D can achieve blood glucose control using the combination of a nutritious meal plan, regular exercise participation, modest weight loss, and medication use (U.S. Department of Health and Human Services 2011). Lifestyle changes that include dietary improvements and regular physical activity are central to diabetes management. When medications are used to control T2D, they should augment lifestyle improvements, not replace them.

Case in Point: Aerobic Exercise Rx for a Typical Older Adult with T2D

DG is a 58-year-old man who has had T2D for at least a decade. Although he golfs for 2–3 h most weekends and does some yard work on occasion, it has been at least 5 years since he has engaged in any structured physical activity, even just regular walking. His motivation to start doing more physical activity comes from the fact that his A1C levels have started creeping up over time, along with his body weight. His doctor put him on exenatide within the past year (in addition to metformin, which he has been on since being diagnosed), but it has only helped him to lose ~10 lb since he started using it. He admits that his job is stressful and that he often puts in long hours that are mostly sedentary in nature (due to lots of meetings and document preparation).

Resting Measurements

Height: 70 inches

Weight: 245 lb

BMI: 35.1 (obese)

Heart rate: 77 beats per minute (bpm)

Blood pressure: 135/85 mmHg (on medication)

Fasting Labs

Plasma glucose: 108 mg/dl (controlled with metformin and exenatide)

A1C: 6.9%

Total cholesterol: 155 mg/dl (on medication)

Triglycerides: 85 mg/dl

High-density lipoprotein cholesterol: 52 mg/dl

Low-density lipoprotein cholesterol: 86 mg/dl

Questions to Consider

1. What type of aerobic exercise should DG consider doing to help lower his blood glucose and his body weight?

2. What exercise frequency, intensity, and duration should DG focus on?

3. How should his exercise training progress over time?

4. Are any precautions needed for DG when he exercises?

(Continued)

ACUTE AND CHRONIC METABOLIC AND PSYCHOLOGICAL EFFECTS OF PHYSICAL ACTIVITY

Engaging in physical activity facilitates glucose uptake, improves insulin sensitivity, and aids in glucose homeostasis, with effects that lower blood glucose levels for 2–72 h after the last bout of activity, depending on exercise duration, intensity, and subsequent food intake (King 1995; Boulé 2001, 2005; O’Gorman 2006). Exercised skeletal muscles continue to take up more blood glucose during the ensuing rest period, with the contraction-mediated pathway persisting for several hours (Ivy 1981, Garetto 1984) and insulin-mediated uptake for longer (Richter 1982, Cartee 1989, King 1995, Bajpeyi 2009). Given that these effects are short in duration, remaining physically active is an essential component of diabetes self-management behavior for all individuals with T2D.

Acute Effects of an Exercise Session

Low to moderate physical activity. In individuals with T2D exercising moderately, muscular uptake of blood glucose usually rises more than hepatic glucose production, and blood glucose levels decline over the course of the activity (Minuk 1981). At the same time, plasma insulin levels fall, making the risk of exercise-induced hypoglycemia low, as long as someone is not taking insulin or insulin secretagogues (Koivisto 1984). Muscular contractions increase blood glucose uptake to supplement muscular glycogen use (Ploug 1984, Richter 1985). As this uptake pathway is contraction induced and distinct from the one triggered by the binding of insulin to a cell surface receptor (Khayat 2002), glucose uptake into working muscle is normal even when insulin-mediated uptake is impaired (as it usually is in T2D) (Colberg 1996, Zierath 1996, Braun 2004). The glucose-lowering effects of acute moderate aerobic exercise are similar whether the physical activity is performed in a single session or multiple bouts with the same total duration (Baynard 2005). Glucose production also shifts from hepatic glycogenolysis to enhanced gluconeogenesis as exercise duration increases (Suh 2007, Wahren 2007).

Blood glucose reductions during any physical activity are related to the duration and intensity of the exercise, pre-exercise control, and state of physical training (Colberg 1996, Boulé 2001, Boulé 2005, Sigal 2007). Although prior physical activity of any intensity generally enhances uptake of circulating glucose for glycogen synthesis (Christ-Roberts 2003, Galbo 2007) and stimulates fat oxidation and storage in muscle (Duncan 2003, Goodpaster 2003, Boon 2007), more prolonged or intense activity acutely enhances insulin action for longer periods of time (Braun 1995, Larsen 1999, Houmard 2004, Evans 2005, Sigal 2007, Bajpeyi 2009). Acute improvements in insulin sensitivity in women with T2D have been found for equivalent energy expenditures whether engaging in low-intensity or high-intensity walking (Braun 1995). Moreover, a single 45 min session of either endurance-type exercise (done at 50% of maximum workload capacity) or resistance work (done at 75% of one-repetition maximum) substantially reduces the prevalence of hyperglycemia during the subsequent 24 h period in individuals with insulin-treated and non–insulin-treated T2D (van Dijk 2012b). These benefits are available even when glycemic control is closer to optimal to start with, as demonstrated in adults with well-controlled T2D (A1C level below 7.0%) who still achieved a 28% reduction in the prevalence of hyperglycemia over the 24 h period following a single bout of moderate-intensity aerobic exercise (van Dijk 2012a). While moderate and vigorous aerobic training improve insulin sensitivity more, a lesser intensity still improves insulin action to some degree (Houmard 2004).

Vigorous physical activity. During brief, intense aerobic exercise, plasma catecholamine levels rise markedly, driving a major increase in blood glucose production (Marliss 2002). As a consequence, hyperglycemia can result and persist for up to 1–2 h, likely because plasma catecholamine levels and glucose production do not return to normal immediately with cessation of the intense activity (Marliss 2002). Exercise fuel use is most affected by the intensity of the activity, with harder workouts causing a greater reliance on carbohydrates as a fuel (Sigal 1994, Braun 1995, Colberg 1996, Kang 1996, Larsen 1999, Manetta 2002, Houmard 2004, Galbo 2007, Bajpeyi 2009). Doing any activity, even a lower-intensity one, causes a shift from predominant reliance on free fatty acids at rest to a blend of fat, glucose, and muscle glycogen, with minimal use of amino acids (Bergman 1999, Burke 1999). More carbohydrate is used during intense activity, as long as sufficient amounts are available in muscle or blood (Colberg 1996, Kang 1996, Borghouts 2002, Boon 2007). Early in exercise, muscular glycogen stores provide the bulk of the fuel for working muscles, but during prolonged activities, as glycogen becomes depleted, muscles increase their uptake and use of circulating blood glucose and free fatty acids released from adipose tissue (Bergman 1999, Kang 1999, Watt 2002). Intramuscular lipid stores are more readily used during longer-duration activities and during recovery from intense activities (Borghouts 2002, Pruchnic 2004, Wang 2009).

Chronic Effects of Aerobic Training

Many long-term studies demonstrate a sustained improvement in glucose control when a regular aerobic training program is maintained (Kirwan 2000, Christ-Roberts 2004, Holten 2004, O’Gorman 2006, Zoppini 2006, Wang 2009). Such training exerts its beneficial effects primarily through increased insulin sensitivity (Boulé 2001, 2005). Studies have shown that structured exercise training that consists of aerobic exercise, resistance training, or a combination of both is associated with A1C reduction in individuals with T2D (Umpierre 2011). It also may be necessary to combine physical activity advice with dietary advice to most effectively lower glycemic levels (Umpierre 2011). In addition to glycemic benefits, chronic training appears to help with loss and maintenance of body weight and reduction of cardiovascular risk factors (Holten 2004, Zoppini 2006, Wang 2009).

There appears to be a graded dose-response relationship between the aerobic exercise training dose (a product of exercise intensity, duration, and frequency) and improvements in insulin sensitivity (Dubé 2012). In one study, exercise intensity has been shown to be significantly related to improvements in insulin sensitivity, whereas frequency may not be, at least in 55 healthy adults undergoing 16 weeks of supervised endurance training (three to five sessions lasting 45 min/week,

with three sessions supervised). Others have shown that engaging in structured exercise training of >150 min/week results in greater glycemic benefits than ≤150 min, so the total exercise dose may be important (Umpierre 2011).

Even 1 week of aerobic training can improve whole-body insulin sensitivity in individuals with T2D, however (Winnick 2008). Training apparently enhances the responsiveness of skeletal muscles to insulin with increased expression or activity of proteins involved in glucose metabolism and insulin signaling (Christ-Roberts 2004, Holten 2004, O’Gorman 2006, Wang 2009). Moderate training may increase glycogen synthase activity and GLUT4 (glucose transporter) protein expression, but not insulin signaling (Christ-Roberts 2004). Fat oxidation is also a key aspect of improved insulin action, and exercise training increases lipid storage in muscle and fat oxidation capacity (Duncan 2003, Goodpaster 2003, Pruchnic 2004, Kelley 2007). Moreover, mitochondrial dysfunction is apparent only in inactive longstanding T2D, which suggests that mitochondrial function and insulin resistance do not depend on each other. Prolonged exercise training can, at least partly, reverse the mitochondrial impairments associated with long-term diabetes (van Tienen 2012).

Recently, low-volume, high-intensity training (HIT) was shown to rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health in subjects with T2D (Little 2011). In that study, subjects were involved in 2 weeks of thrice-weekly exercise that consisted of a total 10 min of exercise (ten 60 s sessions separated by 1 min of rest) done at 90% of maximal HR. That training reduced their blood glucose levels by 13% over the 24 h period following training, as well as postprandial glucose spikes for several days afterward. Given the intensity of such training, however, each individual’s fitness level and cardiovascular risk factors should be carefully considered before HIT is prescribed.

Psychological Benefits of Physical Activity

Exercise likely has psychological benefits for diabetic individuals, although evidence for acute and chronic psychological benefits is limited. In the Look AHEAD (Action for Health in Diabetes) trial, participants in the intensive lifestyle intervention attempted to lose >7% of their initial weight and increase moderate physical activity participation to >175 min/week. They had improvements in health-related (SF-36 physical component scores) quality-of-life and depression symptoms after 12 months that were mediated by enhanced physical fitness (Williamson 2009). When individuals undertake exercise to prevent a chronic disease, however, they fare better psychologically than those who undertake it to manage an existing health problem. Although psychological well-being is improved among individuals who exercise for disease prevention, it deteriorates when undertaken for management of diagnosed cardiovascular disease, end-stage renal disease, pulmonary disease, neurological disorders, and cancer (Gillison 2009). Thus, the benefits of physical activity participation may vary, with individuals starting these activities with fewer existing health complications benefiting the most.

Both short- and long-term exercise participation result in substantial decreases in depressive symptoms in individuals of all ages (Craft 2004) and in clinical depression and depressive symptoms among the elderly (Sjosten 2006). Potential mechanisms include increased self-efficacy, a sense of mastery, distraction, and changes in self-concept, as well as physiological factors like increased central norepinephrine transmission, changes in the hypothalamic adrenocortical system (Droste 2003), serotonin synthesis and metabolism (Dishman 1997), and endorphin release. In any case, regular physical activity participation may improve psychological well-being, health-related quality of life, and depression in individuals with T2D, among whom depression is more common than in the general population (Egede 2003).

Case in Point: Continued

A more thorough discussion with DG reveals that his biggest barrier to doing structured physical activities is a perceived lack of time during the day and the workweek. He is willing to commit, however, to going 3 days/week to a local gym, either at lunchtime or on his way home from work in the evening. Any more than that, however, he has already decided will not fit into his busy work schedule, and he is not willing to do anything on the weekends except for golfing. Also, one of his knees bothers him from time to time (from an old, college football injury), although he ambulates well most of the time without any problems.

Additional Questions to Consider

1. What type of aerobic exercise should DG consider doing that would fit into his thrice-weekly schedule of structured activities?

2. What exercise intensity, frequency, and duration should DG focus on with only 3 days a week of structured exercise?

3. How should his exercise training progress over time, given his stated time and other constraints?

4. Are any precautions needed for DG when he exercises, particularly with regard to his occasional knee issues?

(Continued)

AEROBIC EXERCISE PRESCRIPTION FOR T2D

Mode

Any form of aerobic exercise (including brisk walking) that utilizes large muscle groups and causes sustained increases in heart rate is likely to be beneficial for blood glucose levels and cardiovascular risk management in individuals with T2D (Hu 2001), and undertaking a variety of modes of physical activity is recommended to optimize training effects and lower injury risk (Physical Activity Guidelines Advisory Committee 2008). Examples of acceptable aerobic activities include both weight-bearing and non–weight-bearing ones, including walking, jogging, running, cycling, swimming, water aerobics, aquatic activities, conditioning machines, dancing, chair exercises, rowing, and cross-country skiing, among others. When choosing exercise modes for older and deconditioned individuals in particular, be mindful that walking and moderate-intensity physical activities are associated with a very low risk of musculoskeletal complications, whereas jogging, running, and competitive sports are associated with increased risk of injury (Garber 2011).

Intensity

For optimal fitness gains, aerobic exercise should be at least at a moderate intensity, or 40–59% of heart rate reserve (HRR, as discussed in chapter 4), although vigorous-intensity exercise, defined as 60–89% HRR, is likely to confer greater gains in fitness (Garber 2011, Physical Activity Guidelines Advisory Committee 2008). A severely deconditioned person can start as low as 30% HRR and progress from there to higher moderate levels over time. However, doing even 60 min of low-intensity work (30–39%) can improve blood glucose levels over 24 h in individuals with diabetes, maybe even more so than engaging in only 30 min of high-intensity exercise (Manders 2010).

Using subjective ratings, moderate- to vigorous-intensity exercise corresponds to an overall body rating of “somewhat hard” to “hard” (Garber 2011). Less fit people generally require a higher level of effort to complete the same activity, and their initial subjective intensity may need to be lower than “somewhat hard.” Subjective intensity can be estimated using a scale of 0 to 10, where resting is 0, maximal effort 10, moderate-intensity activity 5–6, and vigorous-intensity activity 7–8 on that scale (Physical Activity Guidelines Advisory Committee 2008).

For most people with T2D, brisk walking is a moderate-intensity exercise due to their lower cardiorespiratory fitness capacity (Boulé 2003). Including some faster intervals, such as pick-up-the-pace training that involves exercising at even 10% above a person’s normal walking or other exercise intensity, can lead to additional fitness gains in individuals with T2D (Johnson 2006, 2008). Greater cardiovascular protection and other benefits may be gained from engaging in vigorous exercise, however, especially if individuals already have a fairly high fitness level or greater physical activity participation. A recent meta-analysis showed that exercise intensity predicts improvements in overall blood glucose control to a greater extent than exercise volume, suggesting that those already fit enough to exercise at a moderate intensity should consider undertaking some vigorous physical activity, at least on occasion, to obtain additional glycemic and cardiovascular benefits (Boulé 2003).

Frequency

Aerobic exercise should be performed at least 3 days/week with no more than 2 consecutive days between bouts of activity due to the short-lived nature of improvements in insulin action (King 1995, Boulé 2005). Most exercise interventions in T2D have used a frequency of three times per week (Boulé 2001, Snowling 2006, Thomas 2006, Sigal 2007), but current guidelines for adults generally recommend five sessions of moderate activity (Haskell 2007, Nelson 2007, Physical Activity Guidelines Advisory Committee 2008). Recently, a study involving adults with diabetes required them to engage in either 30 min of daily, moderate-intensity aerobic activity or 60 min of similar-intensity exercise every other day (van Dijk 2012c). Although both trials substantially reduced the prevalence of hyperglycemia throughout the subsequent day, with total work matched, daily exercise did not lead to further improvements in glycemic control compared with exercise done every other day. The recommended frequency, therefore, is a minimum of 3–5 days/week, with equal caloric expenditure regardless of how many days physical activity is undertaken.

Duration

Individuals with T2D should engage in a minimum of 150 min/week of exercise undertaken at moderate intensity or greater. Aerobic activity should be performed in bouts of at least 10 min and should be spread throughout the week. Around 150 min/week of moderate-intensity exercise is associated with reduced morbidity and mortality in observational studies in all populations (Physical Activity Guidelines Advisory Committee 2008); however, not all health benefits of physical activity occur at 150 min/week, and engaging in less than this amount still benefits deconditioned individuals. As an individual person moves from

150 min/week toward 300 min (5 h) a week, he or she usually gains additional health benefits. The risk of musculoskeletal injury does rise with increasing exercise durations beyond the recommended amounts, but the type and intensity of the exercise are likely more important factors in the incidence of injury, with the volume of exercise (i.e., total work done or calorie expenditure through activities of varying duration, frequency, or intensity) apparently having less importance (Garber 2011).

Most studies in T2D populations have employed durations of 135–150 min/week of activity (Boulé 2001, Snowling 2006, Thomas 2006), even those that included higher-intensity aerobic exercise (Mourier 1997). Unfortunately, most people with T2D lack a sufficient aerobic capacity to work out vigorously enough to meet federal and other physical activity guidelines that allow for a shorter duration of vigorous work (Haskell 2007, Nelson 2007, Physical Activity Guidelines Advisory Committee 2008, Garber 2011). In a meta-analysis, the mean maximal aerobic capacity in diabetic individuals was only 22.4 ml/kg/min (6.4 metabolic equivalents [METs]), making their highest sustainable intensity only a moderate one in absolute terms (i.e., 4.8 METs, or 75% of maximal) (Boulé 2003). Accordingly, most diabetic individuals will require at least 150 min of moderate to vigorous aerobic exercise per week to achieve optimal cardiovascular disease risk reduction, although some glycemic and other health benefits are likely attained from lower exercise doses. Individuals with higher aerobic capacities may be able to exercise at a higher intensity for less time to gain the same benefits.

Progression

Deconditioned individuals need to start out on the low end of the intensity scale and work toward gradual progression of both exercise intensity and volume to minimize the risk of injury or noncompliance, particularly if health complications are present (Physical Activity Guidelines Advisory Committee 2008). Initially, their focus should be on increasing frequency and duration of the exercise rather than intensity. Progression over 4–6 months usually has an ultimate goal of inclusion of vigorous aerobic exercise, but for many with T2D, doing moderate-intensity workouts may be an appropriate endpoint (although frequency and duration may progress over time). See Table 5.1 for a summary of these exercise prescription recommendations for individuals with T2D.

Table 5.1 Recommended Aerobic Exercise Rx for Type 2 Diabetes

Mode	Walking, jogging, cycling, swimming, rowing, aquatic activities, seated exercises, dancing, conditioning machines, and more
Intensity	40–89% HRR (initial intensity may need to be lower, such as 30–39% or light intensity, for sedentary, deconditioned, or overweight individuals) Perceived exertion of “somewhat hard” to “hard” (but possibly easier initial intensity only for sedentary, deconditioned, or overweight individuals)
Frequency	3–7 days/week (including structured and lifestyle activity) No more than 2 consecutive days without any activity
Duration	30–60 min daily, with minimum of 10 min/session At least 150 min/week of moderate- to vigorous-intensity activity
Progression	Start out on the “low” side and progress slowly over weeks to months Increase duration and frequency first, intensity last (with the possible exception of adding in faster intervals during exercise sessions)

HRR, heart rate reserve.

If weight loss is a major goal, a greater duration of exercise may be required to maximize caloric expenditure. The most successful weight-control programs involve combinations of exercise, diet, and behavior modification, and people who successfully maintain a large weight loss report exercising ~7 h/week (Pavlou 1989, Schoeller 1997, Weinsier 2002, Saris 2003, Donnelly 2009).

Case in Point: Wrap-Up

Because DG has been mostly inactive for a while, he should start with an initial exercise prescription that allows him to start “low” and progress slowly to avoid injury and to prevent his knee irritation from returning. Another important aspect of his program will be to increase his unstructured daily movement throughout the day, particularly on days that he does not plan to work out in the gym doing his structured program.

Exercise Program Goals

Mode of Activity: Given DG’s potential for knee issues, his recommended activities to start include stationary cycling, walking on a treadmill, and use of other conditioning machines that are lower impact (such as cross-trainers and elliptical machines).

Intensity: DG should attempt to work up to maintaining a workout pace that feels “somewhat hard” to start, possibly “hard” when he begins to feel more conditioned. On the conditioning machines, he can choose “interval” programs that intersperse harder intervals with easier intervals to gain the most fitness with the least amount of training time. His initial target heart rate should be in the range of 104 to 130 bpm (30–59% HRR), with a later training goal of at least 131 bpm (60% of HRR) due to his limited time in the gym.

Frequency: Because DG has stated that he can only go to the gym 3 days/week, his goal should be to schedule his structured training on 3 nonconsecutive days while increasing his unstructured activities (including golfing) on the other 4 days. In any case, he should avoid letting >2 days lapse without some sustained aerobic activities to optimize his blood glucose management.

Duration: When beginning his exercise program, DG should engage in shorter bouts of exercise training, separated by a rest period, until he can train continuously for 30–60 min. His ultimate training goal is 150 min of physical activity spread throughout the week.

Progression: DG should be advised to focus on increasing the duration of his structured workouts on 3 nonconsecutive days/week to attempt to achieve 150 min/week of moderate or vigorous exercise. Once he has established higher levels of physical fitness, he may choose to do combination training that includes some resistance training on at least 2 of his exercise training days.

Daily Movement: Because of DG’s perceived time limitations and to assist with his weight loss, he should attempt to engage in more daily movement, including fidgeting (such as bouncing or swinging one’s leg repeatedly while seated), standing, and taking more steps. On days that he has no planned exercise schedule, he should attempt to maximize his unstructured activities throughout the day.

Possible Precautions: Because DG has quite a few risk factors for cardiovascular disease (including elevated lipids, hypertension, diabetes, and obesity), he should consider having a checkup with his doctor and possibly having an exercise stress test before starting regular exercise, to determine his initial fitness level, if nothing else, although neither one is absolutely required before his participation in moderate activities like brisk walking. His medications (metformin and exenatide) should not have any effect on his blood glucose responses to exercise or increase his risk for hypoglycemia, but he should be advised to occasionally monitor his responses to bouts of activity as reductions in glucose levels resulting from exercise can be motivating for many individuals.

People with T2D should embrace lifestyle changes that include regular physical activity to maximize their blood glucose management and lower their cardiovascular disease risk. Engaging in physical activity facilitates glucose uptake, improves insulin sensitivity, and aids in glucose homeostasis, with effects that lower blood glucose levels for 2–72 h after the last bout of activity, depending on exercise duration, intensity, and subsequent food intake. Current recommendations for adults with T2D suggest that such individuals should engage in at least 150 min a week of moderate to vigorous aerobic exercise spread out over at least 3 days during the week, with no more than 2 consecutive days between bouts of aerobic activity.

Professional Practice Pearls

• Participation in regular physical activity improves blood glucose control, blood lipids, blood pressure, cardiovascular risk, mortality risk, and quality of life in T2D.

• Given that improvements in insulin action that enhance blood glucose control are short lived, aerobic exercise participation should be regular.

• Although moderate and vigorous aerobic training improve insulin sensitivity more, a lower intensity still improves insulin action to some degree.

• Glucose-lowering effects of moderate aerobic exercise are similar whether the physical activity is performed in a single session or in multiple bouts with the same total duration.

• Participation in vigorous exercise may cause a transient increase in blood glucose levels that can last for several hours due to the release of glucose-raising hormones.

• Individuals with T2D should undertake at least 150 min a week of moderate to vigorous aerobic exercise spread out over at least 3 days during the week, with no more than 2 consecutive days between bouts of aerobic activity.

• Most people with T2D lack a sufficient aerobic capacity to work out vigorously enough to meet physical activity guidelines that allow for a lesser duration of vigorous work.

• Each individual’s fitness level and cardiovascular risk factors should be carefully considered before prescribing low-volume, high-intensity interval training.

• Progress by increasing physical activity gradually over time whenever more activity is necessary to meet guidelines or health goals; inactive individuals should “start low and go slow” by gradually increasing how often and how long activities are done.

• Individuals who successfully maintain a large weight loss report exercising about 7 h/week.

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