Available online at www.sciencedirect.com
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`ELSEVIER
`
`Diabetes Research and Clinical Practice 77S (2007) S87---S91
`
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`Clinical aspects of physical exercise for diabetes/metabolic
`syndrome
`Yuzo Sato a,* , Masaru Nagasaki a, Masakazu Kubota a, Tomoko Uno \ Naoya Nakai c
`
`"Department of Health Science, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin 470-0195, Japan
`b Division of General Education, Aichi Gakuin University, Nisshin 470-0195, Japan
`c Department of Health and Sports Sciences, Graduate School of Medicine, Osaka University, Toyonaka 560-0043, Japan
`
`Accepted 29 January 2007
`Available online 11 May 2007
`
`Abstract
`
`Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In
`the field of diabetes and exercise, among the epidemiological studies of physical exercise, recent mega-trials such as the Diabetes
`Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the
`progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects
`of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles
`and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin
`in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant
`correlation has been observed between delta MCR (llinsulin sensitivity) and the average number of steps performed in a day. Our
`recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in
`part, to increases in GLUT4 protein, IRSl and PB-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise
`of mild to moderate intensity, including walking and jogging, 10--30 min a day, 3-5 days a week, is recommended. Resistance
`training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have
`decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related
`diseases.
`© 2007 Published by Elsevier Ireland Ltd.
`
`Keywords: Diabetes; Metabolic syndrome; Physical exercise; Euglycemic clamp; Insulin resistance
`
`1. Introduction
`
`Evidence-based medicine (EBM) is an important
`component of medical care and research. In the field of
`exercise therapy for diabetes and obesity/metabolic
`syndrome, the results of a number of large-scale
`epidemiological follow-up studies have demonstrated
`
`* Corresponding author. Tel.: +81 561 73 1111;
`fax: +81 561 73 1142.
`E-mail address: satoy@dpc.agu.ac.jp (Y. Sato).
`
`that weight loss resulting from lifestyle modification,
`including physical exercise, is useful for decreasing the
`development of type 2 diabetes among obese people
`with impaired glucose tolerance (IGT). The mechan(cid:173)
`isms of the effects of physical exercise in muscles and
`adipose tissues after physical training have been
`elucidated by molecular biological approaches.
`These and other studies have accumulated evidences
`that suggest the usefulness of physical exercise for the
`prevention and the treatment of diabetes and obesity/
`metabolic syndrome.
`
`0168-8227/$ - see front matter© 2007 Published by Elsevier Ireland Ltd.
`doi: I 0.1 0l 6/j .diabres.2007.01.039
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`S88
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`Y. Sato et al.I Diabetes Research and Clinical Practice 77S (2007) S87--S91
`
`The Japanese Ministry of Health, Labor and Welfare
`has emphasized the concept of lifestyle-related dis(cid:173)
`eases, including type 2 diabetes, obesity, hypertension,
`etc. In addition, Health Japan 21, a large-scale project
`limed at decreasing diabetes and other lifestyle-related
`diseases has been enacted. This project aims to prolong
`active lifespan by reducing obesity and other risk
`factors through physical activity/exercise and modifica(cid:173)
`tion of nutrition/eating habits, and other component of
`lifestyles. As a legal basis for this program, the Health
`Promotion Law was enacted in May 2003 [1,2].
`
`2. Physical activity and diabetes/metabolic
`syndrome: results of epidemiological studies
`
`2.1. Increased insulin resistance caused by lack of
`exercise
`
`In Japan and Korea, most diabetic patients are type 2
`(non-insulin dependent). Decreased insulin secretion
`and insulin resistance play important roles in occur(cid:173)
`rence and progression of type 2 diabetes. Insulin
`resistance
`is exacerbated by aspects of modern
`westernized lifestyle such as overeating (high fat diet),
`sedentary state and stressful daily life.
`Lack of physical exercise induces insulin resistance
`results in compensatory hyperinsulinemia, leading to
`type 2 diabetes, hypertension, hyperlipidemia, and
`atherosclerosis, as well as obesity, playing an important
`role in the development and progression of pathological
`conditions known as syndrome X, multiple-risk-factor
`syndrome, the deadly qualtet, the insulin-resistance
`syndrome and the visceral-fat syndrome [1,2]. Recently,
`notion of metabolic syndrome has been introduced by
`WHO and Japanese Society of Internal Medicine [3].
`
`2.2. Prevention of type 2 diabetes and the role of
`physical exercise
`
`The results of various follow-up studies have
`revealed that the proper diet combined with physical
`exercise is not only useful in preventing type 2 diabetes
`and improving disease status but is also effective in the
`prevention and treatment of all other insulin-resistance(cid:173)
`related diseases (lifestyle-related diseases/metabolic
`syndrome), by improving in vivo sensitivity to insulin
`[l].
`
`(1) The incidence of diabetes decreases by 6% with
`every 500 kcal/week increase in energy consump(cid:173)
`tion in leisure-time physical exercise (Paffenbarger
`Study, USA, 1994).
`
`(2) Although patients with impaired glucose tolerance
`are at high risk for type 2 diabetes and death from
`coronary disease, the implementation of dietary
`counseling and physical exercise lead
`to
`the
`decrease in the mortality of IGT patients to the
`level of individuals with normal glucose tolerance
`(Malmo Study, Sweden 1998) [4].
`(3) The incidence of diabetes mellitus in IGT patients
`decreased by 31 % during a 6-year period when diet
`therapy alone was prescribed, by 46% when exercise
`therapy alone was prescribed, and by 42% when a
`combination of diet and exercise therapy was
`prescribed (Da Qing Study, China, 1997) [5].
`(4) Positive modification of lifestyle habits concerning
`diet and exercise has a greater suppressive effect on
`the development of diabetes than that of the oral
`antihyperglycemic agent metformin (58% versus
`31 % ) (Diabetes Prevention Program, DPP; USA,
`2002) [6].
`
`Although the results of intervention trials have been
`reported from various countries, few studies of this kind
`have been carried out in the field of diabetes prevention
`in Japan. Data from the JDPP (Director: Dr. Kuzuya H.,
`National Kyoto Hospital) have been awaited.
`
`3. Metabolic and endocrinological effects of
`physical exercise
`
`3.1. Acute metabolic effect
`
`(1) In patients in whom metabolic regulation is well
`maintained, exercise promotes the use of glucose
`and free fatty acids (FFA) in muscles. Therefore,
`physical exercise combined with dietary restriction
`has beneficial effects for prevention and treatment
`of metabolic syndrome/obesity. And exercise after
`meals by diabetic patients with relatively good
`glucose control may lead to better control of
`diabetes by suppressing the rapid postprandial
`elevation of blood glucose [2].
`(2) High-intensity exercise may aggravate abnormal
`carbohydrate metabolism through increased secre(cid:173)
`tion of insulin-counter regulatory hormones such as
`glucagon and catecholamine. When diabetes is poorly
`controlled, secretion of these counter regulatory
`hormones is further increased. If diabetic control is
`extremely poor, physical exercise is contraindicated.
`(3) The implementation of moderate-intensity exercise
`[relative intensity up to about 50% of maximum
`oxygen uptake (V 02ma,)] for several minutes causes
`increased utilization of carbohydrate and FFA as
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`Y. Sato et al./Diabetes Research and Clinical Practice 77S (2007) S87--S91
`
`S89
`
`muscle energy sources. However, as exercise
`intensity increases above the lactate threshold
`(LT), the ratio of carbohydrate utilization increases,
`and maximal exercise (anaerobic exercise) depends
`on the glycolytic pathway, using only glucose, not
`lipid, as the source of energy [2].
`
`therapy for diabetes and
`In physical exercise
`metabolic syndrome/obesity, it is necessary to elevate
`the rate of utilization of fat stored in adipose tissue, in
`addition to muscle training. Therefore, exercise of
`moderate or lower intensity (LT level) is preferable [l].
`
`3.2. Training effect
`
`3.2.1. Physical exercise and insulin sensitivity
`(1) Even mild physical exercise that does not affects
`V o2max can cause improvement in the in vivo insulin
`sensitivity if continued for a prolonged period of time
`(Fig. 1). The implementation of dietary restriction
`and physical exercise in obese people and obese
`patients with type 2 diabetes will result in a elective
`decrease of body fat, leading to weight loss, while
`causing no changes in lean body mass (LBM). Thus,
`dietary restriction combined with physical exercise is
`more useful for improving insulin sensitivity than
`dietary restriction alone (Fig. 2). In addition, increase
`in glucose metabolic clearance rate (~MCR) shows a
`positive correlation with
`the number of steps
`performed per day determined by a pedometer [7].
`(2) Aerobic exercise such as jogging is more useful in
`improving in vivo insulin sensitivity than anaerobic
`
`M/1
`0.20
`
`0.15
`
`0.10
`
`0.05
`
`before
`
`12montbs
`4montbs
`lmontb
`-regular jogging-
`
`Fig. 1. Changes in ratio of glucose metabolism (M) to steady-state
`insulin levels (I) during euglycemic clamp before and after long-term
`regular jogging. Values before and after regular jogging were com(cid:173)
`pared using a one-way analysis of variance and were significantly
`different. *p < 0.05 [15].
`
`P<0.01
`
`After
`Before
`Combined diet and
`exercise therapy
`7.8± 0.8
`n=14
`
`~ 3
`§
`·vi = 2
`:e
`"' ~ 1
`5 a 0 '-----''------L-
`
`Weighlloss (kg)
`
`After
`Before
`Diet therapy
`4.2 ± 0.8
`n=lll
`
`Fig. 2. Changes in insulin sensitivity (glucose infusion rate) in
`patients on diet therapy alone and on combined diet and exercise
`therapy (Yamanouchi et al., 1995).
`
`exercise like weightlifting [2] . However, mild
`resistance training, if carry out in an aerobic
`manner, is also useful for elderly patients who
`have decreased muscular strength and mass [8,9].
`(3) Low intensity exercise using the horseback riding
`therapeutic equipment (Joba®) might be useful as
`an auxiliary therapy for the treatment of insulin
`resistance in type 2 diabetes and obesity [ 10] .
`(4) Visceral fat, rather than subcutaneous fat, promotes
`the formation of insulin-resistance-related athero(cid:173)
`sclerosis. Physical exercise combined with dietary
`restriction decreases visceral fat [l]. On the other
`hand, absence of an effect of liposuction from
`abdominal subcutaneous adipose tissue on insulin
`action and risk factors for coronary heart disease
`was reported [11].
`(5) The implementation of exercise brings about a
`decrease in plasma triglyceride level, an increase in
`high-density lipoprotein (HDL) cholesterol, and
`improvement of mild hypertension. Thus, physical
`exercise exerts an inhibitory effect on the develop(cid:173)
`ment and progression of atherosclerosis through a
`number of mechanisms [ l].
`(6) Continued physical exercise increases basal meta(cid:173)
`bolic ratio (BMR), which tends to decrease with
`dietary restriction, and diet-induced thermogenesis
`(DIT) in obese individuals [l].
`(7) Implementation of physical exercise
`physical fitness.
`(8) Physical exercise can improve blood glucose control
`in patients with type 2 diabetes, as mentioned above.
`However, since metabolic status can vary on a daily
`basis in patients with type 1 diabetes mellitus, the
`effect of physical exercise is not necessary constant.
`
`improves
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`Y. Sato et al.I Diabetes Research and Clinical Practice 77S (2007) S87--S91
`
`3.2.2. Mechanisms of training effects
`(1) Improved insulin sensitivity is the major beneficial
`effect of exercise. Muscular factors
`including
`postreceptor steps, such as muscle weight gain,
`glycolytic pathway in muscle, increase in enzyme
`activity in the tricarboxylic acid (TCA) cycle, and
`increase in glucose signal transductions (Fig. 3),
`play major roles in its manifestation [2,12].
`(2) Adipose tissue factors such as decreases in body fat
`and the size of fat tissue decreases, plasma TNF-a
`levels secreted from adipose tissue may decrease
`and secretion of adiponection increase, resulting in
`improved in vivo insulin sensitivity [l,13].
`
`4. Practical aspects of prescribed exercise
`
`4.1. Indications of physical exercise and medical
`check-up
`
`Before patients undertake programs of physical
`exercise, various medical examinations are needed to
`determine that diabetes is in the good controlled
`
`2
`
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`
`s
`
`T
`
`12 wk old
`
`S-S
`
`T-T
`
`S-T
`
`27wkold
`
`Fig. 3. Concentration of GLUT-4 protein in skeletal muscle plasma
`membrane (top) and intracellular membrane (bottom) for 12-week-old
`sedentary (S) and exercise-trained (T) rats; and for 27-week-old
`sedentary rats (S-S) and rats allowed to exercise before maturation
`(T-T) and after maturation (S-T). Signals of immunoreactive GLUT-4
`were measured with a Bio Imaging analyzer. Values are means ± S.E.
`for six rats. * Significant difference from sedentary rats at same age.
`*p < 0.05 (Nakai et al. , 1996).
`
`condition and diabetic patients do not have progressive
`severe complications.
`
`4.2. Type and intensity of exercise
`
`The effect of exercise that manifests in improved
`insulin sensitivity decreases within 3 days after
`exercise, and is no longer apparent after 1 week [ 14] .
`Free fatty acids produced from
`lipolysis
`through
`physical exercise are converted to acetyl coenzyme A
`(CoA) via !3-oxidation, and are metabolized in the
`tricarboxylic acid cycle. Therefore, it is easy to
`understand why the exercises prescribed for exercise
`therapy are restricted to those of an aerobic nature.
`Specifically, moderate-intensity exercise that results
`in V o2max of about 50% (pulse rate of about 120 min -l for
`those in their 50 s or younger and about 100 min- 1 for
`those in their 60 and 70 s, LT level) should be performed
`for 10-30 min at a time (2-3 times a day, preferably after
`meals), at least 3-5 days a week. Recommended types of
`exercise are aerobic exercise that use muscles throughout
`the body, such as walking, jogging, radio gymnastic
`exercises, stationary bicycle exercise, and swimming.
`For the elder diabetic patients with tendency of muscle
`atrophy, mild resistance training such as light dumbbells
`exercise and half squat should be performed in addition to
`aerobic exercise. The horseback riding equipment
`(Joba ®) is also useful for aged patients and patients
`with knee or foot disorders [10].
`Type 2 diabetes is a typical lifestyle-related disease.
`It is necessary to instruct patients to incorporate some
`exercise into their daily life, e.g., getting off the bus at a
`stop before the destination and walking the rest of the
`way. The use of a pedometer and the Lifecorder® are
`useful for motivating patients and for determining how
`much exercise has been performed. The recorded
`figures should be checked during regular inpatient
`rounds or in the outpatient clinic, with the goal set at
`10,000 steps (or at least 7500 steps) per day [2].
`
`4.3. Precautions in implementing physical exercise
`
`(1) If diet therapy is not followed, good controlled
`condition of blood glucose will not be achieved.
`Dietary restriction should be instructed.
`(2) Usually, exercise should be performed after meals.
`(3) In patients on insulin therapy, the insulin dose
`should be reduced prior to physical exercise. If
`exercise extends over a prolonged period of time,
`dietary supplementation is necessary before, during,
`and after exercise. If hypoglycemia occurs during
`exercise, a cola drink or glucose (pet sugar)
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`Y. Sato et al./Diabetes Research and Clinical Practice 77S (2007) S87--S91
`
`S91
`
`Table I
`Yardsticks of energy consumption during exercise
`
`Times required per unit exercise
`
`Type of exercise (energy consumption, kcal/kg/min)
`
`Intensity of
`exercise
`
`Very low
`
`Exercise continued for about 30 min to
`achieve I unit
`
`A stroll (0.0464), on a vehicle: standing in a train or bus (0.0375),
`cooking (0.0481), housework: laundry, cleaning (0.0471-0.0499),
`general clerical work (0.0304), shopping (0.0481), gymnastic exercise:
`low intensity (0.0552)
`Walking: 70 m/min (0.0623), bathing (0.0606), stairs: descending (0.0658),
`radio gymnastic exercise (0.0552--0.1083), bicycle: level ground (0.0658),
`and golf [males (0.0640), females (0.0500)]
`Jogging: mild (0.1384), stairs: ascending (0.1349), bicycle: slope (0.1472),
`cross-country skiing (0.0782-0.1348), skating (0.1437), volleyball (0.1437),
`mountain climbing (0.1048-0.1508), tennis: practice (0.1437)
`Marathon running (0.2959), rope skipping (0.2667), basketball (0.2588), rugby:
`forward (0.2234), swimming: breaststroke (0.1968), kendo (0.2125)
`
`Low
`
`Exercise continued for about 20 min to
`achieve I unit
`
`Moderate
`
`Exercise continued for about IO min to
`achieve I unit
`
`High
`
`Exercise continued for about 5 min to
`achieve I unit
`
`Note: A single unit corresponds to about 80 kcal. It should be used as a yardstick for supplementary feeding in diabetic patients on insulin therapy.
`
`dissolved in lukewarm water should be taken.
`Cookies, cheese, and milk are suitable before and
`after exercise to prevent hypoglycemia. Table 1
`provides a guide to food intake.
`(4) General precautions including the use of sports
`shoes and incorporation of warm-up and cool-down
`exercises should be given.
`
`5. Conclusion
`
`Evidences for the usefulness of physical exercise for
`diabetes and obesity/metabolic syndrome have been
`described, with an outline of the practical aspects of
`exercise prescription. Higher quality guidance
`in
`physical exercise should be expected, particularly in
`term of EBM, i.e., based on the rationale derived from
`recent experimental and clinical studies.
`
`Acknowledgments
`
`This research was supported by Longevity Science
`Research Grants from the Ministry of Health and Labor
`of Japan (93Al 106, H9-025, Hl3-009) and a Grant in
`Aid for Scientific Research from the Ministry of
`Education, Culture, Sports, Science, and Technology of
`Japan (11670066).
`
`References
`
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`48 (2005) 59-63.
`[2] Y. Sato, Diabetes and life-styles: role of physical exercise for
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`[3] Committee to Evaluate Diagnostic Criteria for Metabolic Syn(cid:173)
`drome, Definition and diagnostic criteria for metabolic syn(cid:173)
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`
`[4] K.F. Eriksson, F. Lindgarde, No excess 12-year mortality in men
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`1010-1016.
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`[7] K. Yamanouchi, T. Shinozaki, K. Chikada, T. Nishikawa, K. Ito,
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`[11] S. Klein, L. Fontana, V.L. Young, AR. Coggan, C. Kilo, B.W.
`Patterson, et al., Absence of an effect of liposuction on insulin
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`[12] N. Nakai, Y. Shimomura, J. Sato, Y. Oshida, I. Ohsawa, Y. Sato,
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`lin sensitivity, J. Appl. Physiol. 80 (1996) 1963-1967.
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`
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