Advertisement
Mayo Clinic Proceedings Home

An Obligation for Primary Care Physicians to Prescribe Physical Activity to Sedentary Patients to Reduce the Risk of Chronic Health Conditions

  • Author Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Manu V. Chakravarthy
    Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Affiliations
    Department of Internal Medicine, University of Pennsylvania, Philadelphia
    Search for articles by this author
  • Author Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Michael J. Joyner
    Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Affiliations
    Department of Anesthesiology, Mayo Clinic, Rochester, Minn
    Search for articles by this author
  • Author Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Frank W. Booth
    Correspondence
    Address reprint requests and correspondence to Frank W. Booth, PhD, Department of Biomedical Sciences, University of Missouri, 1600 E Rollins St, E102, Veterinary Medicine Bldg, Columbia, MO 65211
    Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
    Affiliations
    Departments of Biomedical Sciences and Physiology and the Dalton Cardiovascular Institute, University of Missouri, Columbia
    Search for articles by this author
  • Author Footnotes
    1 This study was supported by National Institutes of Health grants AR19393 (F.W.B.), HL46493 (M.J.J.), and HL63328 (M.J.J.).
      Physical inactivity increases the risk of many chronic disorders. Numerous studies have convincingly demonstrated that undertaking and maintaining moderate levels of physical activity (eg, brisk walking 3 hours a week) greatly reduces the incidence of developing many chronic health conditions, most notably type 2 diabetes mellitus, obesity, cardiovascular disease, and many types of cancers. However, the underlying mechanistic details of how physical activity confers such protective effects are not well understood and consequently constitute an active area of research. Although changing an individual's ingrained behavior is commonly perceived to be difficult, encouraging evidence suggests that intensive and repeated counseling by health care professionals can cause patients to become more physically active. Therefore, counseling patients to undertake physical activity to prevent chronic health conditions becomes a primary prevention modality. This article summarizes the vast epidemiologic and biochemical evidence supporting the many beneficial health implications of undertaking moderate physical activity and provides a rationale for incorporating physical activity counseling as part of routine practice in the primary care setting.
      BMI (body mass index), CDC (Centers for Disease Control and Prevention), CHC (chronic health condition)
      One in 10 Americans now die prematurely of disorders with origins related to physical inactivity.
      • Hahn RA
      • Teutsch SM
      • Rothenberg RB
      • Marks JS
      Excess deaths from nine chronic diseases in the United States, 1986.
      • Booth FW
      • Gordon SE
      • Carlson CJ
      • Hamilton MT
      Waging war on modern chronic diseases: primary prevention through exercise biology.
      In 1986,
      annual deaths in the United States from colon cancer, coronary heart disease, and stroke numbered 256,686 in persons aged 18 to 65 years who reported being sedentary or irregularly physically active.
      • Hahn RA
      • Teutsch SM
      • Rothenberg RB
      • Marks JS
      Excess deaths from nine chronic diseases in the United States, 1986.
      Moderate physical activity may annually eliminate 250,000 premature deaths from coronary heart disease, colon cancer, and type 2 diabetes mellitus.
      • Booth FW
      • Gordon SE
      • Carlson CJ
      • Hamilton MT
      Waging war on modern chronic diseases: primary prevention through exercise biology.
      Physical activity is a first-line therapy and protects against many chronic health conditions by improving glucose uptake and insulin sensitivity, improving blood lipid profiles, lowering blood pressure, improving the health of blood vessels, and protecting against obesity.
      • Pate RR
      • Pratt M
      • Blair SN
      • et al.
      Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
      In other words, physical activity could be viewed as primary therapy to prevent other more costly therapies. Emerging evidence suggests that intensive and sustained counseling by health care professionals is effective in increasing the level of physical activity in previ-ously sedentary individuals.
      • Writing Group for the Activity Counseling Trial Research Group
      Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial.
      Therefore, a major aim of this article is to urge the medical community to aggressively counsel sedentary patients to incorporate physical activity as a part of daily life. Increased physical activity may be a clinically effective and economically intelligent means of preventing the burgeoning rise of many chronic health conditions.

      SCOPE OF THE PROBLEM

      Chronic Health Conditions Related to Inactivity

      Chronic health conditions (CHCs) are the most common types of conditions seen in the primary care setting. Their natural history is generally indolent (for example, diabetes mellitus, coronary heart disease, obesity, hypertension, colon cancer), spans many decades, and is usually marked with transient periods of acute exacerbation or alleviation. Unless screened, the affected patient is generally unaware of the problem until end-organ damage occurs. Thus, the person afflicted with a CHC generally lives with the disorder throughout life.
      Chronic health conditions have been a leading public health concern since the 1920s.
      • Hoffman C
      • Rice D
      • Sung HY
      Persons with chronic conditions: their prevalence and costs.
      These conditions now affect more than 100 million individuals in the United States and account for 76% of all direct medical costs,
      • Hoffman C
      • Rice D
      • Sung HY
      Persons with chronic conditions: their prevalence and costs.
      and the incidence of CHCs continues to increase. Obesity and type 2 diabetes mellitus are now considered epidemics by the Centers for Disease Control and Prevention.
      • Mokdad AH
      • Serdula MK
      • Dietz WH
      • Bowman BA
      • Marks JS
      • Koplan JP
      The continuing epidemic of obesity in the United States.
      • Pinhas-Hamiel O
      • Zeitler P
      “Who is the wise man?—the one who foresees consequences”: childhood obesity, new associated comorbidity and prevention.
      Obesity increased 57% in US adults from 1991 to 1999.
      • Koplan JP
      • Dietz WH
      Caloric imbalance and public health policy.
      More than 50% of American adults and nearly 25% of American youth are overweight or obese.
      • Koplan JP
      • Dietz WH
      Caloric imbalance and public health policy.
      • Sokol RJ
      The chronic disease of childhood obesity: the sleeping giant has awakened [editorial].
      Prevalence of type 2 diabetes mellitus in the United States has increased 5-fold since 1958.
      • Harris MI
      • Eastman RC
      Early detection of undiagnosed diabetes mellitus: a US perspective.
      It was once referred to as adult-onset diabetes but is now frequently diagnosed in adolescents.
      Additionally, many CHCs do not begin during early adulthood or in middle age. Sixty percent of overweight 5- to 10-year-old children already have 1 biochemical or clinical cardiovascular risk factor (such as hyperlipidemia), elevated blood pressure, or increased insulin levels, and 25% have 2 or more risk factors.
      • Koplan JP
      • Dietz WH
      Caloric imbalance and public health policy.
      These risk factors observed in children mean that CHCs may become clinically overt earlier in adulthood.
      • Sokol RJ
      The chronic disease of childhood obesity: the sleeping giant has awakened [editorial].
      Thus, effective primary prevention strategies in all age groups would greatly diminish the overall morbidity and mortality associated with CHCs.

      Epidemic Physical Inactivity

      Approximately 70% of US adults either do not undertake physical activity or are underactive, and nearly half of America's youth (aged 12-21 years) are not vigorously active on a regular basis.
      • Centers for Disease Control and Prevention
      If physical activity is such a potent primary preventive medicine, why is it not more popular? One possibility is that the word “exercise” elicits a negative response in many people. Exercise may suggest intense activity that is associated with pain, specialized equipment, or membership in a health club. Also, some individuals may have negative feelings about exercise due to experiences as children and teenagers if their lack of athletic abilities evoked ridicule from peers. However, undertaking even moderate physical activity (ie, activity performed at 3-6 times the basal metabolic rate, which is the equivalent of brisk walking at 3-4 mph for 30 minutes each day in most healthy adults
      • Pate RR
      • Pratt M
      • Blair SN
      • et al.
      Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
      ) is protective against many CHCs.
      While health clubs and personal trainers serve a purpose for some individuals, completely sedentary individuals will benefit from increasing physical activity within the structure of their own daily living. Such a concept is termed functional physical activity and could contribute to personal health, as well as the overall health of the nation. Therefore, we suggest that instead of approaching exercise as a time-consuming ordeal, physicians should explain to their sedentary patients that physical activities such as walking or bicycling 10 to 15 minutes twice a day instead of driving a short distance, parking on the far side of the mall parking lot instead of driving around for the closest space, climbing stairs, and doing yard work will all be beneficial. Likewise, playing with children or grandchildren and restricting time watching television are other ways to increase physical activity in those 70% of Americans who perform less than the 30 minutes a day of moderate activities as recommended by the US surgeon general.
      • Centers for Disease Control and Prevention

      Physical Inactivity and Aging

      Three weeks of continuous bed rest by healthy volunteers was associated with muscle wasting, bone loss, insulin resistance, 30% reductions in maximal cardiac output and stroke volume, orthostatic intolerance, decreased immune function, and decreased physical capacity.
      • Saltin B
      • Blomqvist G
      • Mitchell JH
      • Johnson Jr, RL
      • Wildenthal K
      • Chapman CB
      Response to exercise after bed rest and after training: a longitudinal study of adaptive changes in oxygen transport and body composition.
      These are changes that also occur with aging, and physical inactivity directly contributes to them. In this context, progressive regimens of resistance exercise training improve muscle strength and size in frail elderly (90-year-old) people.
      • Fiatarone MA
      • Marks EC
      • Ryan ND
      • Meredith CN
      • Lipsitz LA
      • Evans WJ
      High-intensity strength training in nonagenarians: effects on skeletal muscle.
      These changes are accompanied by improvement in mobility, an increased level of spontaneous physical activity, ability to carry out activities of daily living, and dynamic balance, which in turn reduces falls.
      • Fiatarone MA
      • O'Neill EF
      • Ryan ND
      • et al.
      Exercise training and nutritional supplementation for physical frailty in very elderly people.
      Many of these beneficial effects of exercise are appreciated only if regular physical activity is maintained. However, from clinical experience, it is well known that implementation of programs to consistently maintain increased physical activity in the elderly population is challenging. Using physical activity promotion programs such as the Community Health Activities Model Program for Seniors (CHAMPS II),
      • Stewart AL
      • Verboncoeur CJ
      • McLellan BY
      • et al.
      Physical activity outcomes of CHAMPS II: a physical activity promotion program for older adults.
      95% of those aged 65 to 90 years randomly assigned to the intervention group completed the 1-year program during which they increased both moderate-intensity energy expenditure by 46% or 487 kcal/wk (equivalent to adding a 20-minute-mile brisk walk 5 times a week) as well as light- and moderate-intensity physical activity by 36% or 687 kcal/wk (equivalent to the brisk walking plus lighter activities). Thus, physical activity programs can be effectively promoted in older people and serve as a key strategy to limit the impact of aging on our society.

      DO GENES OR ENVIRONMENT CAUSE CHCs?

      Environmental Change Underlying the Increased Incidence of CHCs

      Only a small percentage of all diseases are produced by a single gene defect.
      • Beaudet AL
      • Scriver CR
      • Sly WS
      • Valle D
      Genetics, biochemistry, and molecular basis of variant human phenotypes.
      Most diseases, and in particular chronic diseases, are determined by the dynamic interaction of multiple genes with the environment. This poorly understood interaction determines whether a specific threshold of biological importance is crossed and overt clinical symptoms associated with a particular disease occur.
      • Beaudet AL
      • Scriver CR
      • Sly WS
      • Valle D
      Genetics, biochemistry, and molecular basis of variant human phenotypes.
      Additionally, on a population basis, genes change slowly and the environment can change rapidly. As noted by the recent CDC report,
      • Mokdad AH
      • Serdula MK
      • Dietz WH
      • Bowman BA
      • Marks JS
      • Koplan JP
      The continuing epidemic of obesity in the United States.
      the “genes related to obesity are not responsible for the epidemic of obesity because the US gene pool did not change significantly between 1991 and 1999.” The much-publicized search for genes causing obesity and diabetes can only broadly determine genes responding to changes in the environment, eg, lifestyle,
      • Beaudet AL
      • Scriver CR
      • Sly WS
      • Valle D
      Genetics, biochemistry, and molecular basis of variant human phenotypes.
      • Campbell L
      • Rossner S
      Management of obesity in patients with type 2 diabetes.
      which in turn is a key initiating factor. Taken together, the concept is that the environment we live in and our lifestyles affect our cellular environment, and our genes respond to these subcellular changes by a pathologic over- or underexpression of various gene products and consequent clinical manifestations of disease. It is logical then to presume that primary preventive medicine would reverse the changes in the cellular environment and thus diminish or even eliminate the occurrence of CHCs such as obesity and diabetes mellitus.
      With this general idea as a background, then from a practical point of view, physicians can counsel changes in lifestyle more easily and effectively than they can treat inherent gene sequences in a living human being. This measure alone would produce an immediate positive impact for the more than 100 million Americans afflicted with a variety of chronic conditions.
      • Hoffman C
      • Rice D
      • Sung HY
      Persons with chronic conditions: their prevalence and costs.
      Our general position is supported by anthropological evidence. Cultures that depended on physical activity (eg, hunter-gatherers) for their daily survival expended more energy per unit of body weight,
      • Diamond JM
      Human evolution: diabetes running wild.
      suggesting that genes may have evolved to support higher rates of metabolism than are present in today's sedentary society. When food is plentiful, it would be beneficial for humans to gain weight as a buffer against future famine. When humans became modernized, energy intake and, particularly, energy output (physical work) decreased compared with hunter-gatherer societies.
      • Diamond JM
      Human evolution: diabetes running wild.
      • Neel JV
      • Weder AB
      • Julius S
      Type II diabetes, essential hypertension, and obesity as “syndromes of impaired genetic homeostasis”: the “thrifty genotype” hypothesis enters the 21st century.
      Affluent humans also consume a greater percentage of dietary fat, gain weight, and develop chronic diseases such as diabetes mellitus and hypertension.
      • Diamond JM
      Human evolution: diabetes running wild.
      • Zimmet P
      Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted?.
      Therefore, it appears that the genes that evolved in generations that had physically active lifestyles and less certain food supplies maladapt to sedentary affluent living.
      • Cockram CS
      The epidemiology of diabetes mellitus in the Asia-Pacific region.
      • Neel JV
      Diabetes mellitus: a “thifty” genotype rendered detrimental by “progress”?.
      Sedentary individuals do not oxidize enough food to keep their genes expressing enough of the proteins (ie, glucose transporters, beneficial lipoproteins, and vasodilating substances) to prevent the modern-day metabolic and circulatory dysfunctions.

      How Cellular and Molecular Mechanisms of Physical Activity Prevent CHCs

      Physical activity improves the expression of genes contributing to health in 3 possible ways. (1) Exercise training has been shown to improve endothelium-dependent vasodilation in both coronary arteries and resistance vessels, thus protecting against heart disease and hypertension. This protection is mediated via an increase in nitric oxide synthase activity and protein level in the vessels, which produces vasodilation, increases structural diameter of blood vessels, and is antiatherogenic.
      • Hambrecht R
      • Wolf A
      • Gielen S
      • et al.
      Effect of exercise on coronary endothelial function in patients with coronary artery disease.
      (2) Complete bed rest for 3 days produces glucose intolerance, mimicking type 2 diabetes. Contraction of limb muscles reverses insulin resistance by stimulating the translocation of the glucose transporter GLUT4 to the sarcolemma of the myofiber and also by inducing the production of more GLUT4 protein. Exercise signals these effects independent of the insulin-signaling pathway allowing those with diabetes to lower blood glucose levels.
      • Goodyear LJ
      • Kahn BB
      Exercise, glucose transport, and insulin sensitivity.
      Such effects explain the long-standing observation that insulin dosage must be decreased when diabetic patients exercise. (3) Blood triglyceride levels increase less after a meal if an exercise bout was undertaken approximately 18 hours earlier, probably because of the increase in lipoprotein lipase activity and protein production.
      • Herd SL
      • Kiens B
      • Boobis LH
      • Hardman AE
      Moderate exercise, postprandial lipemia, and skeletal muscle lipoprotein lipase activity.
      The proteins responsible for the adaptations listed above emphasize the predominant role that physical inactivity has in altering the cellular environment to permit a threshold of biological importance to be passed such that an individual is affected with overt clinical disease.
      Finally, the recent sequencing of the human genome may eventually lead to individualized genetic medicine and new drugs and gene therapies to prevent or treat chronic diseases. However, these new treatments are likely to be expensive. How will the 44 million Americans without health insurance
      • Davis K
      Universal coverage in the United States: lessons from experience of the 20th century.
      afford these expensive diagnostic tests and pharmaceuticals for easily preventable diseases? In addition, costs for private insurance and taxes for governmental health programs will exponentially rise to pay for expensive gene-based medications to replace the prescription of safe, scientifically proven primary prevention modalities such as habitual physical activity and/or dietary modifications to combat CHCs. Such increases in health care costs will only add to the complex and vicious cycle in our health care system, which in our opinion will make delivery of basic clinical care more inaccessible for even more of our population.

      WHAT TO DO AND WHY

      Moderate Physical Activity to Prevent CHCs

      Epidemiologic and interventional data now indicate unequivocally that individuals who perform even minimal physical activity have important reductions in chronic disease. In the Harvard nurses’ studies,
      • Manson JE
      • Hu FB
      • Rich-Edwards JW
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      • Hu FB
      • Sigal RJ
      • Rich-Edwards JW
      • et al.
      Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.
      • Hu FB
      • Stampfer MJ
      • Colditz GA
      • et al.
      Physical activity and risk of stroke in women.
      a prospective study of 72,000 women aged 45 to 65 years demonstrated a dramatic 30% reduction in the incidences of coronary heart disease, stroke, and type 2 diabetes simply by brisk walking (<3 mph) for at least 3 hours a week, compared with those in the study who did less than 3 hours of brisk walking each week. A threshold of 3 mph was found to be necessary to decrease the risk of coronary heart disease in this study, whereas the speed of walking per se is unim portant in the prevention of gains in body fat. A lack of physical activity is the risk factor most consistently shown to be associated with an increased risk of colon cancer.
      • Tomeo CA
      • Colditz GA
      • Willett WC
      • et al.
      Harvard Report on Cancer Prevention: volume 3: prevention of colon cancer in the United States.
      Accumulating epidemiologic evidence also indicates that obese individuals who are physically active have a lower incidence of developing many chronic diseases, compared with their unfit obese counterparts. As illustrated by the Physicians’ Health Study
      • Manson JE
      • Nathan DM
      • Krolewski AS
      • Stampfer MJ
      • Willett WC
      • Hennekens CH
      A prospective study of exercise and incidence of diabetes among US male physicians.
      (n=21,271), when obese individuals become physically active, the risk of CHCs begins to return to that of the unfit normal-weight individual. When compared with physicians with a BMI less than 23 kg/m2, physicians with a BMI higher than 26.4 kg/m2 had a 7-fold increased risk of developing type 2 diabetes if they exercised vigorously (defined as any activity that resulted in working up a sweat) less than once per week.
      • Manson JE
      • Nathan DM
      • Krolewski AS
      • Stampfer MJ
      • Willett WC
      • Hennekens CH
      A prospective study of exercise and incidence of diabetes among US male physicians.
      This increased risk was reduced to 4-fold in physicians of equal BMI (<26.4 kg/m2) who exercised vigorously more than once per week. Thus, these findings suggest that physical activity independent of obesity lowers the risk of type 2 diabetes. Similarly, in the Harvard study of 72,000 nurses,
      • Manson JE
      • Hu FB
      • Rich-Edwards JW
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      the relative risk of having acute coronary events was demonstrated to be 85% higher in those with a BMI higher than 29 kg/m2 and having the lowest total physical activity, compared with the most active nurses with a BMI lower than 29 kg/m2. However, physically active nurses with a BMI higher than 29 kg/m2 had only a 28% higher risk of developing acute coronary events when compared with the most active nurses with a BMI lower than 29 kg/m2, whereas the group with a BMI lower than 29 kg/m2 and the lowest total physical activity had a 46% higher risk.
      • Manson JE
      • Hu FB
      • Rich-Edwards JW
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      Taken together, such epidemiologic data provide a rational basis to suggest that physical inactivity is an important independent risk factor for the development of morbid CHCs. They also suggest a negative synergy between inactivity and other risk factors.
      Furthermore, physical inactivity in patients with multiple chronic conditions has been reported to be associated with twice the rate of subsequent mortality over a short (42- month) follow-up period than that of more active people.
      • Martinson BC
      • O'Connor PJ
      • Pronk NP
      Physical inactivity and short-term all-cause mortality in adults with chronic disease.
      The authors of this study suggested that clinical and population-based interventions to increase physical activity in such patients might have the potential to decrease mortality and costs of care. Importantly, timing of when to undertake physical activity is not age dependent. Individuals who become active in later life by way of a moderate-intensity walking program and who make only modest gains in fitness nevertheless reduce their chronic disease risk.
      • Dunn AL
      • Marcus BH
      • Kampert JB
      • Garcia ME
      • Kohl III, HW
      • Blair SN
      Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial.
      • Tuomilehto J
      • Lindstrom J
      • Eriksson JG
      • Finnish Diabetes Prevention Study Group
      • et al.
      Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
      High-intensity physical activity is not needed to lower the risk of CHCs. For example, moderate exercise (about 2½/2 hours of walking each week) and a low-fat diet produced a 58% reduction in the development of type 2 diabetes (a 71% reduction occurred for those ≥60 years old).
      • National Institute of Diabetes and Digestive and Kidney Diseases
      Diet and exercise dramatically delay type 2 diabetes: diabetes medication metformin also effective.
      Indeed, the Diabetes Prevention Program clinical trial
      • National Institute of Diabetes and Digestive and Kidney Diseases
      Diet and exercise dramatically delay type 2 diabetes: diabetes medication metformin also effective.
      ended a year early because of the dramatic health benefits accrued over its 3-year course. The subjects started the trial with impaired glucose tolerance (a condition that often precedes overt diabetes) and BMIs of 34 kg/m2 but ended with a 5% to 7% sustained loss in body weight. Other participants randomized to a different treatment group receiving only metformin reduced the incidence of type 2 diabetes by 31%, indicating that lifestyle measures and exercise were twice as good as this drug. Additionally, randomized controlled studies by Ross et al
      • Ross R
      • Dagnone D
      • Jones PJ
      • et al.
      Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial.
      elegantly demonstrated that weight loss that was induced by daily physical activity without energy restriction was more effective than diet-induced weight loss in markedly reducing truncal obesity and insulin resistance in men.

      Sedentary Behaviors in Children

      Of greater concern is also the compromise in the health of our future generation. Children are now more physically inactive. For example, they now often use buses to transport themselves to school, lack recess, do not have physical education classes, and watch an average of 3 hours of television a day.
      • Mokdad AH
      • Bowman BA
      • Ford ES
      • Vinicor F
      • Marks JS
      • Koplan JP
      The continuing epidemics of obesity and diabetes in the United States.
      The decrease in childhood physical play is associated with the doubling of childhood obesity in the past 20 years.
      • Flegal KM
      • Ogden CL
      • Wei R
      • Kuczmarski RL
      • Johnson CL
      Prevalence of overweight in US children: comparison of US growth charts from the Centers for Disease Control and Prevention with other reference values for body mass index.
      Concurrent with the decline in childhood physical play is the corresponding rise in the number of television- watching hours. A recent report by Crespo et al
      • Crespo CJ
      • Smit E
      • Troiano RP
      • Bartlett SJ
      • Macera CA
      • Andersen RE
      Television watching, energy intake, and obesity in US children: results from the third National Health and Nutrition Examination Survey, 1988-1994.
      concluded that the prevalence of obesity is lowest among children watching no more than 1 hour of television a day and highest among those watching 4 or more hours a day. Ironically, many think that they are protecting their children from harm by preventing them from playing outside while unknowingly placing their children at a different risk, a sedentary lifestyle in front of the television. In addition to obesity, time spent watching television was also significantly associated with higher risk for diabetes and atherosclerosis risk factors such as decreased high-density lipoprotein cholesterol and increased triglyceride levels, even after adjustment for age, smoking, physical activity levels, and other covariates, as elegantly demonstrated by Hu et al
      • Hu FB
      • Leitzmann MF
      • Stampfer MJ
      • Colditz GA
      • Willett WC
      • Rimm EB
      Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men.
      and Kronenberg et al.
      • Kronenberg F
      • Pereira MA
      • Schmitz MK
      • et al.
      Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.
      Taken together, these studies further corroborate the importance of reducing sedentary behavior at young ages in order to prevent CHCs later in life. Active children grow into sedentary lifestyles. We must encourage children and adolescents not to become sedentary, so that an active lifestyle in children becomes an ingrained behavior and does not need to be encouraged later in life.

      Barriers to Physical Activity

      An alteration in our basic cultural framework and thinking is necessary to combat the alarming increases in CHCs. Multiple factors in present-day society discourage physical activity. Automated processes have replaced manual labor.
      • Diamond JM
      Human evolution: diabetes running wild.
      • Zimmet P
      Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted?.
      A communicable disease with a fairly rapid and acute onset (such as flu) causes greater public health concern than do epidemics of CHCs (which are indolent and noncommunicable diseases, but which kill more people per year and cost more to manage
      • Booth FW
      • Gordon SE
      • Carlson CJ
      • Hamilton MT
      Waging war on modern chronic diseases: primary prevention through exercise biology.
      ). Counseling is believed to be ineffective in reducing CHCs. Patients lack the interest or readiness to undertake physical activity.

      Physical Activity Prescription

      The amount of physical inactivity required to exceed a threshold of biological importance and produce an overt clinical disease varies with the individual.
      • Perusse L
      • Bouchard C
      Genotype-environment interaction in human obesity.
      Consensus reports have commonly recommended moderate activity (eg, brisk walking) rather than hard physical activity (eg, running or working out at <80% of aerobic capacity) in the context of population health.
      • Pate RR
      • Pratt M
      • Blair SN
      • et al.
      Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
      • Katzmarzyk PT
      • Gledhill N
      • Shephard RJ
      The economic burden of physical inactivity in Canada.
      Those individuals with a family history of a chronic disease require more physical activity to lower their elevated risk. Therefore, it will be impossible to provide a single physical activity prescription for all. In the spirit of the oath to do no harm to your patients, it seems reasonable to suggest that sedentary patients in relatively good health undertake brisk walking or stair climbing. Based on several reports,
      • Centers for Disease Control and Prevention
      • Manson JE
      • Hu FB
      • Rich-Edwards JW
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      • Hu FB
      • Sigal RJ
      • Rich-Edwards JW
      • et al.
      Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.
      • Hu FB
      • Stampfer MJ
      • Colditz GA
      • et al.
      Physical activity and risk of stroke in women.
      • US Preventive Services Task Force
      if completely sedentary and underactive individuals participate in moderate physical activity 30 minutes a day on most days of the week (3 hrs/wk), they would obtain at least a 30% reduction in risk for coronary artery disease, stroke, type 2 diabetes, and colon cancer, 4 of the biggest “killers” in present-day America. Once the 70% of Americans who are inactive
      • Pate RR
      • Pratt M
      • Blair SN
      • et al.
      Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
      • Centers for Disease Control and Prevention
      achieve 30 minutes of moderate physical activity each day, then additional increases in daily activity would further lower the risk of chronic disease.
      Despite the obvious evidence supporting the numerous benefits of physical activity in preventing CHCs (Table 1), only 22% to 48% of patients receive advice from their physicians to increase their level of physical activity.
      • Glasgow RE
      • Eakin EG
      • Fisher EB
      • Bacak SJ
      • Brownson RC
      Physician advice and support for physical activity: results from a national survey.
      A recent study of 362 physicians
      • Petrella RJ
      • Wight D
      An office-based instrument for exercise counseling and prescription in primary care: the Step Test Exercise Prescription (STEP).
      found that the 3 leading barriers to exercise prescription were (1) inadequate time for dedicated patient education and counseling to encourage physical activity, (2) lack of necessary skills and tools for providing such counseling, and (3) lack of reimbursement from health insurance and managed care plans for physical activity-related preventive health maintenance and treatment programs. A review of 8 trials that reported an assessment of the effectiveness of advice in routine primary care consultations concluded that brief and sporadic counseling during such routine office visits was not an effective means of producing sustained increases in physical activity.
      • Lawlor DA
      • Hanratty B
      The effect of physical activity advice given in routine primary care consultations: a systematic review.
      Table 1Summary of Common Chronic Health Conditions in Which Physical Activity Has a Direct Role in Modulating Positive Outcomes
      AIDS = acquired immunodeficiency syndrome; COPD = chronic obstructive pulmonary disease; FGF-2 = fibroblast growth factor 2; GLUT4 = glucose transporter 4; HIV = human immunodeficiency virus; IGF-I = insulin-like growth factor I; MI = myocardial infarction; tPA = tissue-type plasminogen activator; VLDL = very-low-density lipoprotein.
      Clinical manifestation of physical inactivityBenefits of increased daily physical activityReferencesPotential cellular/molecular mechanisms underlying the benefits of physical activityReferences
      ObesityReduces total abdominal and visceral adiposity in a dose-response manner
      • Ross R
      • Janssen I
      Physical activity, total and regional obesity: dose-response considerations.
      ,
      • National Task Force on the Prevention and Treatment of Obesity
      Overweight, obesity, and health risk.
      Unknown
      Diabetes mellitus type 2Increases insulin sensitivity of the exercising skeletal muscle and whole-body glucose tolerance
      • Goodyear LJ
      • Kahn BB
      Exercise, glucose transport, and insulin sensitivity.
      Increased translocation of GLUT4 protein to sarcolemma
      • Goodyear LJ
      • Kahn BB
      Exercise, glucose transport, and insulin sensitivity.
      ,
      • Tsao TS
      • Li J
      • Chang KS
      • et al.
      Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity.
      DyslipidemiaIncreases clearance of blood total triglycerides, chylomicrons, and VLDL by exercising muscle
      • Ross R
      • Janssen I
      Physical activity, total and regional obesity: dose-response considerations.
      Increases gene transcription and protein levels for fatty acid uptake, transfer, and oxidation
      • Kiens B
      • Lithell H
      Lipoprotein metabolism influenced by training-induced changes in human skeletal muscle.
      AtherosclerosisIncreases luminal diameter of coronary arteries
      • Hambrecht R
      • Wolf A
      • Gielen S
      • et al.
      Effect of exercise on coronary endothelial function in patients with coronary artery disease.
      Nitric oxide inhibits vascular smooth muscle cell proliferation, platelet aggregation, and monocyte adherence
      • Kokkinos PF
      • Narayan P
      • Colleran JA
      • et al.
      Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.
      HypertensionRegular exercise reduces resting blood pressure and decreases left ventricular hypertrophy in African American men with severe hypertension
      • Kokkinos PF
      • Narayan P
      • Colleran JA
      • et al.
      Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.
      ,
      • Fagard RH
      Exercise characteristics and the blood pressure response to dynamic physical training.
      Smooth muscle dilatory effects on vascular endothelium mediated by nitric oxide
      • Sessa WC
      • Pritchard K
      • Seyedi N
      • Wang J
      • Hintze TH
      Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
      VascularHigher resting and exercise stroke volumes, lower resting and submaximal exercise heart rates, and increased capillary density
      Cardiovascular
       Angina/MILowers death risk by 20%-25% after MI
      • Miller TD
      • Balady GJ
      • Fletcher GF
      Exercise and its role in the prevention and rehabilitation of cardiovascular disease.
       Congestive heart failureImproves endothelial function, skeletal muscle aerobic metabolism, stroke volume (via less afterload)
      • Hambrecht R
      • Gielen S
      • Linke A
      • et al.
      Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial.
      Endothelial-derived nitric oxide produces relaxation of adjacent smooth muscle cells
      • Kokkinos PF
      • Narayan P
      • Colleran JA
      • et al.
      Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.
      ,
      • Muller JM
      • Myers PR
      • Laughlin MH
      Vasodilator responses of coronary resistance arteries of exercise-trained pigs.
      Cerebrovascular
       Ischemic strokeReduction in risk of total and ischemic stroke in a dose-response manner in women
      • Hu FB
      • Stampfer MJ
      • Colditz GA
      • et al.
      Physical activity and risk of stroke in women.
      ,
      • Wannamethee SG
      • Shaper AG
      Physical activity and the prevention of stroke.
      Lowers blood pressure, plasma fibrinogen, platelet aggregation, and plasma tPA activity
      • Wannamethee SG
      • Shaper AG
      Physical activity and the prevention of stroke.
      Peripheral vascular disease
       Intermittent claudicationIncreases maximal treadmill walking distance by 179 m
      • Leng GC
      • Fowler B
      • Ernst E
      Exercise for intermittent claudication.
      Increases vascular relaxation mediated by nitric oxide in blood vessels and increases collateral blood vessels
      • Sessa WC
      • Pritchard K
      • Seyedi N
      • Wang J
      • Hintze TH
      Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
      Pulmonary
       AsthmaMay lower development of asthma
      • Ram FS
      • Robinson SM
      • Black PN
      Effects of physical training in asthma: a systematic review.
      Physical training improves cardiopulmonary fitness without changing lung function
      • Ram FS
      • Robinson SM
      • Black PN
      Effects of physical training in asthma: a systematic review.
       COPDDyspnea can be improved despite the presence of fixed structural abnormalities in the lung
      • Bourjeily G
      • Rochester CL
      Exercise training in chronic obstructive pulmonary disease.
      Improved respiratory muscle function, breathing pattern as well as reduction in anxiety
      • Bourjeily G
      • Rochester CL
      Exercise training in chronic obstructive pulmonary disease.
       Obstructive sleep apneaWeight loss
      • Ross R
      • Janssen I
      Physical activity, total and regional obesity: dose-response considerations.
      Unknown
      Malignancy
       BreastDecreased risk
      • Verloop J
      • Rookus MA
      • van der Kooy K
      • van Leeuwen FE
      Physical activity and breast cancer risk in women aged 20-54 years.
      Unknown
       ColonDecreased risk
      • Tomeo CA
      • Colditz GA
      • Willett WC
      • et al.
      Harvard Report on Cancer Prevention: volume 3: prevention of colon cancer in the United States.
      ,
      • McTiernan A
      • Ulrich C
      • Slate S
      • Potter J
      Physical activity and cancer etiology: associations and mechanisms.
      Unknown
       PancreaticDecreased risk
      • Michaud DS
      • Giovannucci E
      • Willett WC
      • Colditz GA
      • Stampfer MJ
      • Fuchs CS
      Physical activity, obesity, height, and the risk of pancreatic cancer.
      Unknown
      Degenerative conditions
       SarcopeniaResistance training improves muscle strength and size, improves mobility, and increases spontaneous activity
      • Fiatarone MA
      • Marks EC
      • Ryan ND
      • Meredith CN
      • Lipsitz LA
      • Evans WJ
      High-intensity strength training in nonagenarians: effects on skeletal muscle.
      Mainly improves neural recruitment of existing but underused skeletal muscle with enhanced muscle mass synthesis
      • Fiatarone MA
      • Marks EC
      • Ryan ND
      • Meredith CN
      • Lipsitz LA
      • Evans WJ
      High-intensity strength training in nonagenarians: effects on skeletal muscle.
       Physical frailtyPostpones disability and enhances independent living even in the oldest-old subjects
      • Carter ND
      • Kannus P
      • Khan KM
      Exercise in the prevention of falls in older people: a systematic literature review examining the rationale and the evidence.
      ,
      • Spirduso WW
      • Cronin DL
      Exercise dose-response effects on quality of life and independent living in older adults.
      Increases muscle strength
      • Carter ND
      • Kannus P
      • Khan KM
      Exercise in the prevention of falls in older people: a systematic literature review examining the rationale and the evidence.
       Osteopenia/osteoporosisDelays the decrease of bone mineral density
      • Bonaiuti D
      • Shea B
      • Iovine R
      • Cochrane Musculoskeletal Group
      • et al.
      Exercise for preventing and treating osteoporosis in postmenopausal women [protocol].
      Loading of bone
      • Bonaiuti D
      • Shea B
      • Iovine R
      • Cochrane Musculoskeletal Group
      • et al.
      Exercise for preventing and treating osteoporosis in postmenopausal women [protocol].
      Infection/immunity
       HIV/AIDSIncreases cardiopulmonary fitness, CD4 count, psychological status, and quality of life
      • Nixon S
      • O'Brien K
      • Glazier RH
      • Wilkins AL
      Aerobic exercise interventions for people with HIV/AIDS (Cochrane Review).
      Unknown; however, moderate exercise improves the immune system while intense exercise suppresses it
      Musculoskeletal
       Rheumatoid arthritisRegular exercise does not exacerbate pain or accelerate disease progression
      • O'Grady M
      • Fletcher J
      • Ortiz S
      Therapeutic and physical fitness exercise prescription for older adults with joint disease: an evidence-based approach.
      ,
      • Van Den Ende CH
      • Vliet Vlieland TP
      • Munneke M
      • Hazes JM
      Dynamic exercise therapy for rheumatoid arthritis.
      Unknown
       Low back painHelps chronic low back pain patients return to normal daily activities and work
      • van Tulder M
      • Malmivaara A
      • Esmail R
      • Koes B
      Exercise therapy for low back pain: a systematic review within the framework of the Cochrane Collaboration back review group.
      Unknown
      NeurologicRunning enhances neurogenesis, water maze performance, and long-term potentiation
      • van Praag H
      • Christie BR
      • Sejnowski TJ
      • Gage FH
      Running enhances neurogenesis, learning, and long-term potentiation in mice.
      Exercise induces brain IGF-I, which in turn mediates its protective effects by enhancing cerebellar angiogenesis, hippocampal survival of newborn cells, brain norepinephrine, serotonin, brain-derived neurotrophic factor, and FGF-2 levels
      • Carro E
      • Trejo JL
      • Busiguina S
      • Torres-Aleman I
      Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy.
       Alzheimer diseaseWomen with higher levels of baseline physical activity are less likely to develop cognitive decline
      • Yaffe K
      • Barnes D
      • Nevitt M
      • Lui LY
      • Covinsky K
      A prospective study of physical activity and cognitive decline in elderly women: women who walk.
      Unknown
       Multiple sclerosisImproved functional performance, quality of life, and fatigue associated with the disease
      • Petajan JH
      • Gappmaier E
      • White AT
      • Spencer MK
      • Mino L
      • Hicks RW
      Impact of aerobic training on fitness and quality of life in multiple sclerosis.
      Unknown
      Recovery after surgery, immobilization, injury, debilitating illnessesDecreases morbidity, mortality, and rehospitalizations while improving quality of life, depression scores, and physical functioning
      • Ades PA
      • Coello CE
      Effects of exercise and cardiac rehabilitation on cardiovascular outcomes.
      Unknown
      Smoking cessationExercise training as a sole intervention does not appear to enhance smoking cessation
      • Ussher MH
      • West R
      • Taylor AH
      • McEwen A
      • Cochrane Tobacco Addiction Group
      Exercise interventions for smoking cessation (Cochrane Review).
      Unknown
      Psychiatric/psychologic
      DepressionAntidepressant and anxiolytic effects
      • Lawlor DA
      • Hopker SW
      The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials.
      Unknown
      GallstonesDecreases risk of cholecystectomy independent of other risk factors for gallstone disease, such as obesity
      • Leitzmann MF
      • Rimm EB
      • Willett WC
      • et al.
      Recreational physical activity and the risk of cholecystectomy in women.
      Improves glucose tolerance, blood lipid levels, and cholecystokinin release while reducing estrogen exposure
      • Leitzmann MF
      • Rimm EB
      • Willett WC
      • et al.
      Recreational physical activity and the risk of cholecystectomy in women.
      * AIDS = acquired immunodeficiency syndrome; COPD = chronic obstructive pulmonary disease; FGF-2 = fibroblast growth factor 2; GLUT4 = glucose transporter 4; HIV = human immunodeficiency virus; IGF-I = insulin-like growth factor I; MI = myocardial infarction; tPA = tissue-type plasminogen activator; VLDL = very-low-density lipoprotein.
      Health care professionals can be successful in getting sedentary individuals to become physically active, and thus improve health by 2 other means. First, a more intensive and sustained exercise counseling strategy has been shown to be effective in causing patients to increase their level of physical activity. For example, the proportion of those undertaking 30 minutes of moderate physical activity at least 5 days per week was increased from 1% or 2% to 26% (in women) and to 30% (in men) after 22 contacts for physical activity counseling in primary care practices (totaling 3 hours of counseling by visits, calls, and newsletters over 2 years in 50-year-old healthy patients).
      • Writing Group for the Activity Counseling Trial Research Group
      Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial.
      The outcome was that maximal aerobic capacity improved 5% in all counseled female patients (including those not meeting the goal of 30 minutes 5 days a week of moderate physical activity). Such an increase in aerobic capacity would equate to about a 9% reduction in all-cause mortality risk in men
      • Blair SN
      • Kohl III, HW
      • Barlow CE
      • Paffenbarger Jr, RS
      • Gibbons LW
      • Macera CA
      Changes in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men.
      ; similar approximations are not available in women. Incidentally, physician-mediated counseling has also been shown to be effective in causing obese patients to lose weight.
      • Galuska DA
      • Will JC
      • Serdula MK
      • Ford ES
      Are health care professionals advising obese patients to lose weight?.
      • Hu FB
      • Manson JE
      • Stampfer MJ
      • et al.
      Diet, lifestyle, and the risk of type 2 diabetes mellitus in women.
      Thus, it is reasonable to speculate that active and close involvement of physicians in conjunction with other health care professionals (nurses, dietitians, psychologists) would be effective in mediating changes in patients’ behavior.
      Second, physicians’ effectiveness in getting their sedentary patients to be physically active extends beyond their offices; physicians can influence policies related to promoting physical activity in the community. For example, some physicians act as team physicians and influence sports practices. As participation in physical activity is often related to the ease of using areas for physical activity, health care professionals could provide school boards with the health reasons for recesses, physical education classes, after-hours recreation, play areas, and limiting the availability of unhealthy snack foods in school settings.
      • Wing RR
      • Goldstein MG
      • Acton KJ
      • et al.
      Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity.
      Likewise, as retirement facility and nursing home populations increase, health care professionals could promote the availability of equipment and trainers for older individuals to delay the onset of physical frailty.
      The health gain obtained by completely sedentary patients who undertake moderate physical activity is equal to or greater than the gains experienced by individuals who are already physically active and increase their level of activity. Thus, physical activity counseling should become an integral component of routine practice in the primary care setting. It is difficult to imagine a more effective approach to improving our nation's health.

      REFERENCES

        • Hahn RA
        • Teutsch SM
        • Rothenberg RB
        • Marks JS
        Excess deaths from nine chronic diseases in the United States, 1986.
        JAMA. 1990; 264: 2654-2659
        • Booth FW
        • Gordon SE
        • Carlson CJ
        • Hamilton MT
        Waging war on modern chronic diseases: primary prevention through exercise biology.
        J Appl Physiol. 2000; 88: 774-787
        • Pate RR
        • Pratt M
        • Blair SN
        • et al.
        Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
        JAMA. 1995; 273: 402-407
        • Writing Group for the Activity Counseling Trial Research Group
        Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial.
        JAMA. 2001; 286: 677-687
        • Hoffman C
        • Rice D
        • Sung HY
        Persons with chronic conditions: their prevalence and costs.
        JAMA. 1996; 276: 1473-1479
        • Mokdad AH
        • Serdula MK
        • Dietz WH
        • Bowman BA
        • Marks JS
        • Koplan JP
        The continuing epidemic of obesity in the United States.
        JAMA. 2000; 284: 1650-1651
        • Pinhas-Hamiel O
        • Zeitler P
        “Who is the wise man?—the one who foresees consequences”: childhood obesity, new associated comorbidity and prevention.
        Prev Med. 2000; 31: 702-705
        • Koplan JP
        • Dietz WH
        Caloric imbalance and public health policy.
        JAMA. 1999; 282: 1579-1581
        • Sokol RJ
        The chronic disease of childhood obesity: the sleeping giant has awakened [editorial].
        J Pediatr. 2000; 136: 711-713
        • Harris MI
        • Eastman RC
        Early detection of undiagnosed diabetes mellitus: a US perspective.
        Diabetes Metab Res Rev. 2000; 16: 230-236
        • Centers for Disease Control and Prevention
        Physical Activity and Health: A Report of the Surgeon General. US Dept of Health and Human Services, Atlanta, Ga1996 (Accessibility verified January 10, 2002.)
        • Saltin B
        • Blomqvist G
        • Mitchell JH
        • Johnson Jr, RL
        • Wildenthal K
        • Chapman CB
        Response to exercise after bed rest and after training: a longitudinal study of adaptive changes in oxygen transport and body composition.
        Circulation. 1968; 38: 1-78
        • Fiatarone MA
        • Marks EC
        • Ryan ND
        • Meredith CN
        • Lipsitz LA
        • Evans WJ
        High-intensity strength training in nonagenarians: effects on skeletal muscle.
        JAMA. 1990; 263: 3029-3034
        • Fiatarone MA
        • O'Neill EF
        • Ryan ND
        • et al.
        Exercise training and nutritional supplementation for physical frailty in very elderly people.
        N Engl J Med. 1994; 330: 1769-1775
        • Stewart AL
        • Verboncoeur CJ
        • McLellan BY
        • et al.
        Physical activity outcomes of CHAMPS II: a physical activity promotion program for older adults.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M465-M470
        • Beaudet AL
        • Scriver CR
        • Sly WS
        • Valle D
        Genetics, biochemistry, and molecular basis of variant human phenotypes.
        in: Scriver CR Beaudet AL Sly WS Valle D 7th ed. The Metabolic and Molecular Bases of Inherited Disease. Vol 1. McGraw-Hill, New York, NY1995: 79
        • Campbell L
        • Rossner S
        Management of obesity in patients with type 2 diabetes.
        Diabet Med. 2001; 18: 345-354
        • Diamond JM
        Human evolution: diabetes running wild.
        Nature. 1992; 357: 362-363
        • Neel JV
        • Weder AB
        • Julius S
        Type II diabetes, essential hypertension, and obesity as “syndromes of impaired genetic homeostasis”: the “thrifty genotype” hypothesis enters the 21st century.
        Perspect Biol Med. 1998; 42: 44-74
        • Zimmet P
        Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted?.
        J Intern Med. 2000; 247: 301-310
        • Cockram CS
        The epidemiology of diabetes mellitus in the Asia-Pacific region.
        Hong Kong Med J. 2000; 6: 43-52
        • Neel JV
        Diabetes mellitus: a “thifty” genotype rendered detrimental by “progress”?.
        Am J Hum Genet. 1962; 14: 353-362
        • Hambrecht R
        • Wolf A
        • Gielen S
        • et al.
        Effect of exercise on coronary endothelial function in patients with coronary artery disease.
        N Engl J Med. 2000; 342: 454-460
        • Goodyear LJ
        • Kahn BB
        Exercise, glucose transport, and insulin sensitivity.
        Annu Rev Med. 1998; 49: 235-261
        • Herd SL
        • Kiens B
        • Boobis LH
        • Hardman AE
        Moderate exercise, postprandial lipemia, and skeletal muscle lipoprotein lipase activity.
        Metabolism. 2001; 50: 756-762
        • Davis K
        Universal coverage in the United States: lessons from experience of the 20th century.
        J Urban Health. 2001; 78: 46-58
        • Manson JE
        • Hu FB
        • Rich-Edwards JW
        • et al.
        A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
        N Engl J Med. 1999; 341: 650-658
        • Hu FB
        • Sigal RJ
        • Rich-Edwards JW
        • et al.
        Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.
        JAMA. 1999; 282: 1433-1439
        • Hu FB
        • Stampfer MJ
        • Colditz GA
        • et al.
        Physical activity and risk of stroke in women.
        JAMA. 2000; 283: 2961-2967
        • Tomeo CA
        • Colditz GA
        • Willett WC
        • et al.
        Harvard Report on Cancer Prevention: volume 3: prevention of colon cancer in the United States.
        Cancer Causes Control. 1999; 10: 167-180
        • Manson JE
        • Nathan DM
        • Krolewski AS
        • Stampfer MJ
        • Willett WC
        • Hennekens CH
        A prospective study of exercise and incidence of diabetes among US male physicians.
        JAMA. 1992; 268: 63-67
        • Martinson BC
        • O'Connor PJ
        • Pronk NP
        Physical inactivity and short-term all-cause mortality in adults with chronic disease.
        Arch Intern Med. 2001; 161: 1173-1180
        • Dunn AL
        • Marcus BH
        • Kampert JB
        • Garcia ME
        • Kohl III, HW
        • Blair SN
        Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial.
        JAMA. 1999; 281: 327-334
        • Tuomilehto J
        • Lindstrom J
        • Eriksson JG
        • Finnish Diabetes Prevention Study Group
        • et al.
        Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
        N Engl J Med. 2001; 344: 1343-1350
        • National Institute of Diabetes and Digestive and Kidney Diseases
        Diet and exercise dramatically delay type 2 diabetes: diabetes medication metformin also effective.
        (Accessibility verified December 3, 2001.)
        • Ross R
        • Dagnone D
        • Jones PJ
        • et al.
        Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial.
        Ann Intern Med. 2000; 133: 92-103
        • Mokdad AH
        • Bowman BA
        • Ford ES
        • Vinicor F
        • Marks JS
        • Koplan JP
        The continuing epidemics of obesity and diabetes in the United States.
        JAMA. 2001; 286: 1195-1200
        • Flegal KM
        • Ogden CL
        • Wei R
        • Kuczmarski RL
        • Johnson CL
        Prevalence of overweight in US children: comparison of US growth charts from the Centers for Disease Control and Prevention with other reference values for body mass index.
        Am J Clin Nutr. 2001; 73: 1086-1093
        • Crespo CJ
        • Smit E
        • Troiano RP
        • Bartlett SJ
        • Macera CA
        • Andersen RE
        Television watching, energy intake, and obesity in US children: results from the third National Health and Nutrition Examination Survey, 1988-1994.
        Arch Pediatr Adolesc Med. 2001; 155: 360-365
        • Hu FB
        • Leitzmann MF
        • Stampfer MJ
        • Colditz GA
        • Willett WC
        • Rimm EB
        Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men.
        Arch Intern Med. 2001; 161: 1542-1548
        • Kronenberg F
        • Pereira MA
        • Schmitz MK
        • et al.
        Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.
        Atherosclerosis. 2000; 153: 433-443
        • Perusse L
        • Bouchard C
        Genotype-environment interaction in human obesity.
        Nutr Rev. 1999; 57: S31-S37
        • Katzmarzyk PT
        • Gledhill N
        • Shephard RJ
        The economic burden of physical inactivity in Canada.
        CMAJ. 2000; 163: 1435-1440
        • US Preventive Services Task Force
        Guide to Clinical Preventive Services: Report of the US Preventive Services Task Force. 2nd ed. Williams & Wilkins, Baltimore, Md1996
        • Ross R
        • Janssen I
        Physical activity, total and regional obesity: dose-response considerations.
        Med Sci Sports Exerc. 2001; 33: S521-S527
        • National Task Force on the Prevention and Treatment of Obesity
        Overweight, obesity, and health risk.
        Arch Intern Med. 2000; 160: 898-904
        • Tsao TS
        • Li J
        • Chang KS
        • et al.
        Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity.
        FASEB J. 2001; 15: 958-969
        • Kiens B
        • Lithell H
        Lipoprotein metabolism influenced by training-induced changes in human skeletal muscle.
        J Clin Invest. 1989; 83: 558-564
        • Kokkinos PF
        • Narayan P
        • Colleran JA
        • et al.
        Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.
        N Engl J Med. 1995; 333: 1462-1467
        • Fagard RH
        Exercise characteristics and the blood pressure response to dynamic physical training.
        Med Sci Sports Exerc. 2001; 33: S484-S492
        • Sessa WC
        • Pritchard K
        • Seyedi N
        • Wang J
        • Hintze TH
        Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.
        Circ Res. 1994; 74: 349-353
        • Miller TD
        • Balady GJ
        • Fletcher GF
        Exercise and its role in the prevention and rehabilitation of cardiovascular disease.
        Ann Behav Med. 1997; 19: 220-229
        • Muller JM
        • Myers PR
        • Laughlin MH
        Vasodilator responses of coronary resistance arteries of exercise-trained pigs.
        Circulation. 1994; 89: 2308-2314
        • Hambrecht R
        • Gielen S
        • Linke A
        • et al.
        Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial.
        JAMA. 2000; 283: 3095-3101
        • Wannamethee SG
        • Shaper AG
        Physical activity and the prevention of stroke.
        J Cardiovasc Risk. 1999; 6: 213-216
        • Leng GC
        • Fowler B
        • Ernst E
        Exercise for intermittent claudication.
        Cochrane Database Syst Rev. 2000; 2 (CD00990)
        • Ram FS
        • Robinson SM
        • Black PN
        Effects of physical training in asthma: a systematic review.
        Br J Sports Med. 2000; 34: 162-167
        • Bourjeily G
        • Rochester CL
        Exercise training in chronic obstructive pulmonary disease.
        Clin Chest Med. 2000; 21: 763-781
        • Verloop J
        • Rookus MA
        • van der Kooy K
        • van Leeuwen FE
        Physical activity and breast cancer risk in women aged 20-54 years.
        J Natl Cancer Inst. 2000; 92: 128-135
        • McTiernan A
        • Ulrich C
        • Slate S
        • Potter J
        Physical activity and cancer etiology: associations and mechanisms.
        Cancer Causes Control. 1998; 9: 487-509
        • Michaud DS
        • Giovannucci E
        • Willett WC
        • Colditz GA
        • Stampfer MJ
        • Fuchs CS
        Physical activity, obesity, height, and the risk of pancreatic cancer.
        JAMA. 2001; 286: 921-929
        • Carter ND
        • Kannus P
        • Khan KM
        Exercise in the prevention of falls in older people: a systematic literature review examining the rationale and the evidence.
        Sports Med. 2001; 31: 427-438
        • Spirduso WW
        • Cronin DL
        Exercise dose-response effects on quality of life and independent living in older adults.
        Med Sci Sports Exerc. 2001; 33: S598-S608
        • Bonaiuti D
        • Shea B
        • Iovine R
        • Cochrane Musculoskeletal Group
        • et al.
        Exercise for preventing and treating osteoporosis in postmenopausal women [protocol].
        Cochrane Database Syst Rev. 2001;
        • Nixon S
        • O'Brien K
        • Glazier RH
        • Wilkins AL
        Aerobic exercise interventions for people with HIV/AIDS (Cochrane Review).
        Cochrane Database Syst Rev. 2001; 1 (CD001796)
        • O'Grady M
        • Fletcher J
        • Ortiz S
        Therapeutic and physical fitness exercise prescription for older adults with joint disease: an evidence-based approach.
        Rheum Dis Clin North Am. 2000; 26: 617-646
        • Van Den Ende CH
        • Vliet Vlieland TP
        • Munneke M
        • Hazes JM
        Dynamic exercise therapy for rheumatoid arthritis.
        Cochrane Database Syst Rev. 2000; 2 (CD000322)
        • van Tulder M
        • Malmivaara A
        • Esmail R
        • Koes B
        Exercise therapy for low back pain: a systematic review within the framework of the Cochrane Collaboration back review group.
        Spine. 2000; 25: 2784-2796
        • van Praag H
        • Christie BR
        • Sejnowski TJ
        • Gage FH
        Running enhances neurogenesis, learning, and long-term potentiation in mice.
        Proc Natl Acad Sci U S A. 1999; 96: 13427-13431
        • Carro E
        • Trejo JL
        • Busiguina S
        • Torres-Aleman I
        Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy.
        J Neurosci. 2001; 21: 5678-5684
        • Yaffe K
        • Barnes D
        • Nevitt M
        • Lui LY
        • Covinsky K
        A prospective study of physical activity and cognitive decline in elderly women: women who walk.
        Arch Intern Med. 2001; 161: 1703-1708
        • Petajan JH
        • Gappmaier E
        • White AT
        • Spencer MK
        • Mino L
        • Hicks RW
        Impact of aerobic training on fitness and quality of life in multiple sclerosis.
        Ann Neurol. 1996; 39: 432-441
        • Ades PA
        • Coello CE
        Effects of exercise and cardiac rehabilitation on cardiovascular outcomes.
        Med Clin North Am. 2000; 84: 251-265
        • Ussher MH
        • West R
        • Taylor AH
        • McEwen A
        • Cochrane Tobacco Addiction Group
        Exercise interventions for smoking cessation (Cochrane Review).
        Cochrane Database Syst Rev. 2001;
        • Lawlor DA
        • Hopker SW
        The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials.
        BMJ. 2001; 322: 763-767
        • Leitzmann MF
        • Rimm EB
        • Willett WC
        • et al.
        Recreational physical activity and the risk of cholecystectomy in women.
        N Engl J Med. 1999; 341: 777-784
        • Glasgow RE
        • Eakin EG
        • Fisher EB
        • Bacak SJ
        • Brownson RC
        Physician advice and support for physical activity: results from a national survey.
        Am J Prev Med. 2001; 21: 189-196
        • Petrella RJ
        • Wight D
        An office-based instrument for exercise counseling and prescription in primary care: the Step Test Exercise Prescription (STEP).
        Arch Fam Med. 2000; 9: 339-344
        • Lawlor DA
        • Hanratty B
        The effect of physical activity advice given in routine primary care consultations: a systematic review.
        J Public Health Med. 2001; 23: 219-226
        • Blair SN
        • Kohl III, HW
        • Barlow CE
        • Paffenbarger Jr, RS
        • Gibbons LW
        • Macera CA
        Changes in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men.
        JAMA. 1995; 273: 1093-1098
        • Galuska DA
        • Will JC
        • Serdula MK
        • Ford ES
        Are health care professionals advising obese patients to lose weight?.
        JAMA. 1999; 282: 1576-1578
        • Hu FB
        • Manson JE
        • Stampfer MJ
        • et al.
        Diet, lifestyle, and the risk of type 2 diabetes mellitus in women.
        N Engl J Med. 2001; 345: 790-797
        • Wing RR
        • Goldstein MG
        • Acton KJ
        • et al.
        Behavioral science research in diabetes: lifestyle changes related to obesity, eating behavior, and physical activity.
        Diabetes Care. 2001; 24: 117-123

      Linked Article