Exercise and Diabetes. Sheri R. Colberg

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