Exercise is medicine: exercise and metabolic syndrome.

Exercise is arguably the best, safest, and most clinically useful medicine for metabolic syndrome because of its ability to sensitize the body to insulin's action. Understanding the mechanism by which different exercise modalities work is an important first step in understanding how to prescribe it. Another important consideration for any medication, including exercise, is compliance. Exercise prescription for metabolic syndrome should avoid doing harm and set the patient up for success.

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Aerobic Exercise Mechanism of Action

The first thing most physicians will think of when it comes to exercise prescription is aerobictype exercise. Walking, jogging, bike-riding, and other cardiovascular centered activities seem to be of particular benefit for metabolic syndrome. Type 1 muscle fibers are the endurance fibers of muscle and are the predominant fiber activated in aerobic exercise. These fibers are a rich source of GLUT4 receptors in the body. GLUT4 is an insulin-responsive glucose receptor that is translocated to the cell membrane from secondary signals upon insulin receptor binding. It appears that when the body begins to lose sensitivity to insulin, this defect is not an issue of insulin binding to its receptor, but rather a disruption of the secondary messengers responsible for moving the GLUT4 receptor to the cell membrane. This is why the muscle mass of an individual determines 40% of his or her insulin sensitivity and 70% to 90% of blood glucose clearance. (7), (8) Exercise seems to be able to reverse this effect through non-insulin-dependent mechanisms and restore GLUT4 levels on the cell membrane, thus reducing blood glucose load. (6-8) The ability to lower the glucose load is one of the most powerful steps in reversing insulin resistance. An acute bout of exercise has been shown to be able to restore insulin sensitivity for 16 hours in both normal and diabetic populations. (1) There are different aerobic modalities that physicians should be aware of. The exercise protocol, intensity, and duration play an important role in the clinical outcome. Each also has its pros and cons in terms of compliance.

What Type of Cardiovascular Exercise Is Best?

The first thing most physicians and exercise-motivated patients will think of is walking or jogging. One recent study published in American Journal of Cardiology in December 2007 out of Duke University showed some interesting results concerning exercise intensity and duration in regard to the metabolic syndrome. (2) This study separated 227 men and women who all had elements of metabolic syndrome into three exercise interventions. Group 1 engaged in a lower intensity exercise program that amounted to walking 10 to 11 miles per week, a total time of between 20 and 30 minutes per day. Group 2 completed the same distance but did so at a faster jogging pace. Group 3 exercised at the same jogging pace as group 2, yet covered almost twice the distance, 20 miles. There was also an inactive control group.

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Surprisingly, the low-intensity walking group saw significantly more improvement in their scoring on the US National Cholesterol Education Program Adult Treatment Panel III (ATPIII), a scoring system for metabolic syndrome, than the jogging group who completed the same distance. However, the 20-mile joggers enjoyed the most dramatic improvement. This study hints that both duration and intensity play a role, but that duration may be most important. Both the low-intensity walkers and the longer-distance joggers would have been spending about the same amount of time exercising per day, hinting that the duration of exercise was the primary factor involved, although intensity also played a role.

A more recent article in July 2008 in Circulation compared interval training, a technique involving more intense exercise alternated with relative rest, to traditional aerobic exercise. (3) The aerobic group exercised for 47 minutes 3 times a week at an intensity of 70% of maximum heart rate, walking on an inclined treadmill. The interval group performed four 4-minutes intervals at 90% maximum heart rate followed by 3 minutes of active recovery at 70% maximum heart rate, adjusting the treadmill speed and inclines to achieve the desired intensity. Counting their warm-up and cool-down, the interval group spent 40 minutes exercising 3 times each week. At the end of the 16-week study, the interval group had superior outcomes in aerobic capacity, endothelial function, insulin signaling, and muscle mass production, as well as reduced blood glucose and lipogenesis. This same interval procedure has been duplicated in adolescents as well with similar results. (4) Interestingly, participants seemed to prefer the interval protocol. The authors stated, "They found it motivating to have a varied procedure to follow during each training session, whereas those in the more traditional group found it 'quite boring' to walk continuously during the whole exercise period." Taken together, the above studies and others like them give physicians some choice as to which modality to prescribe. Walking, traditional jogging, and interval training all confer significant benefit for very little time commitment, usually ranging from 3.5 hours per week for walking or jogging to 2 hours for interval-type exercise. However, given that time is the number one reason cited for lack of exercise participation, interval training may become a more favorable option.

Resistance Training to Improve Insulin Sensitivity

In addition to aerobic exercise, resistance training is now understood to play an important and unique role in insulin resistance. A fascinating new study published in the February 2008 issue of Cell Metabolism shows that stimulation of the growth of muscle fibers has substantial effects on liver glucose metabolism. (5) In this study, it was shown that growth of specific type 2 muscle fibers reversed the insulin resistance caused by a high-fat, high-sugar diet in mice. Of the 1,200-plus genes involved in liver insulin resistance, the growth stimulus on muscle fibers was able to affect 800 or so of these genes to revert to normal function. Since type 2 muscle fibers are primarily activated in explosive sprinting and weight training, type-1 dominated aerobic exercise would not be expected to produce the same results. While the mechanism is not understood, the authors speculated that myokines (cytokines released form muscle tissue) might play a role.

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Exercise Prescription

Based on the above considerations, a meaningful exercise prescription for metabolic syndrome should start with a strong base of cardiovascular exercise, but also make use of the more potent and synergistic interval and resistance modalities. Walking, jogging, and interval training all provide unique benefits with little time investment. For the less motivated and more obese, a simple daily walking program for 30 to 40 minutes daily would be a good start. However, for those who are motivated, want more substantial results, or are prone to become bored, exercise prescription should be more varied. A mix of modalities would seem to be most beneficial.

An optimal fitness program for metabolic syndrome would involve walking 30 minutes on most days. Adding 2 days of resistance training with a focus on targeting type 2 muscles fibers is key. This would entail a full-body workout using the major muscle groups, like chest, back, and legs. Remember, time is a factor, so the workout should be kept short and the patient instructed to choose weights that allow 8 to 12 repetitions for 3 to 5 sets. To round out the conditioning program, 1 to 2 days of interval training should be done. A good starting place for beginners is a work-to-rest ratio of 1 minute of hard exertion followed by 2 minutes of active rest, for a total workout time of 20 to 40 minutes. Finally, 1 to 2 days of jogging would work to bolster insulin sensitivity and provide variety.

Notes

(1.) Borghouts LB, Keizer HA. Exercise and insulin sensitivity: a review. Int J Sports Med. 2000;21(1):1-12.

(2.) Johnson JL, Slentz CA, Houmard JA, et al. Exercise training amount and intensity effects on metabolic syndrome (from studies of a targeted risk reduction intervention through defined exercise). Am J Cardiol. 2007;100(12):1759-1766.

(3.) Tjonna AE, Lee SJ, Rognmo O, et al. Aerobic interval training vs. continuous moderate exercise as a treatment for metabolic syndrome. Circulation. 2008;118:346-354.

(4.) Schjerve IE, Tyldum GA, Tjonna AE, et al. Both aerobic endurance and strength training programmes improve cardiovascular health in obese adults. Clin Sci. 2008;115:283-293.

(5.) Izumiya Y, Hopkins T, Morris C, et al. Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 2008;7(2):159-172.

(6.) Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. 4th ed. Thompson Wadsworth; 2005.

(7.) Nistala R, Stump CS. Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome. J Cardiometab Syndr. 2006;1(1):47-52.

(8.) Bruning JC, Michael MD, Winnay JN, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell. 1998;2(5):559-569.

by Jade Teta, ND, CSCS, and Keoni Teta, ND, LAc, CSCS

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