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physical activity, in turn, may influence physiological capacity, psychological health, dietary intake, and other adverse behaviours or risk factors for chronic disease. All of these are potential pathways by which exercise could ultimately influence the prevalence of chronic disease in a population. Other than genetic factors and environmental insults (pollution, asbestos, heavy metals, infectious agents, etc.), most of the significant contributors to the development or severity of chronic diseases are in some way related to habitual levels of physical activity. Examples include cardiovascular disease, stroke, type 2 diabetes,¹⁴⁸ obesity, hypertension, osteoarthritis, depression,¹¹⁰ and osteoporosis, among others.^1,7

      Although appropriate levels of physical activity may optimise risk factor profiles, the presence of risk factors may lead to reduced physical activity and thus heightened risk of disease. For example, inactivity may lead to loss of muscle mass, followed by muscle weakness and further restriction in activity levels, subsequently contributing to the development of osteopenia and gait abnormalities and, finally, hip fracture.

      Although observational studies can never completely separate the effects of physical activity from genotype or other unmeasured characteristics of individuals who self‐select an active lifestyle, the best studies attempt to control for demographic differences and other known risk factors for the incident disease and eliminate early or occult disease at baseline if possible prior to analysis. Thus, for example, exercise reduces the risk of cardiovascular disease by ~50%, even after controlling for such risk factors as smoking, obesity, hypertension, and dyslipidaemia. Longitudinal cohort studies have generally confirmed the cross‐sectional data linking exercise to reduced disease risk. Of particular interest are studies in which middle‐aged sedentary adults with low fitness levels have become fit at follow‐up and have markedly reduced cardiovascular mortality compared with those remaining unfit or inactive. These findings suggest that preventive exercise prescriptions instituted in middle age or beyond may be as important as those initiated at younger ages.

      Randomised clinical trial data are available for the prevention of some diseases with exercise (e.g., secondary cardiovascular events, diabetes mellitus, and osteoporotic fracture) but are not yet available for others (stroke, dementia, depression). Diabetes is clearly preventable in high‐risk obese adults with impaired glucose tolerance randomised to exercise and diet, as shown in the Finnish Diabetes Study⁸² and the Diabetes Prevention Program (DPP), among others.¹⁴⁹ Similarly to Finnish subjects, DPP participants randomly assigned to the intensive lifestyle intervention of diet and exercise reduced their risk of incident type 2 diabetes by 58% by 3 years compared to control (lifestyle advice only), and significantly better than metformin prescription. Of particular interest is the finding that those over the age of 60 responded best, with a 71% reduction in incident diabetes in this time frame, while metformin was no better than the control condition in this older age group.

The major diseases and syndromes for which exercise may be beneficial as a preventive strategy are listed in Table 7.6, along with the postulated mechanisms of exercise benefit and the specific modality of exercise most relevant for these outcomes.

Table 7.6 Potential mechanisms by which exercise can prevent disease.

Disease or syndrome	Postulated mechanisms of exercise effect	Recommended exercise modality
Arthritis	Decreased body weightMaintenance of cartilage integrityMaintenance of muscle and tendon strength	Aerobic exercise Resistance exercisea
Cancer (breast, colon, prostate)	Decreased body fatDecreased oestrogen levelsAltered dietary intakeDecrease in gastrointestinal transit timeIncreased prostaglandin F2	Aerobic exercise Resistance exercisea
Chronic renal failure	Reduced risk of hypertensionReduced risk of type 2 diabetes mellitus	Aerobic exercise Resistance exercisea
Congestive heart failure	Decreased risk of ischaemic heart diseaseDecreased risk of hypertensionDecreased risk of type 2 diabetes mellitus	Aerobic exercisea Resistance exercisea
Coronary artery disease	Decreased blood pressureDecreased LDL cholesterolIncreased HDL cholesterolDecreased fibrinogenDecreased total body fat, visceral fatDecreased insulin resistance, hyperinsulinaemiaDecreased cortisol levels, inflammatory cytokinesIncreased adherence to smoking cessation, dietary behavioursDecreased depression, anxietyImproved endothelial cell function	Aerobic exercise Resistance exercise
Dementia	Improved cerebral blood flowIncreased neurotrophic factors in CNSHippocampal neurogenesisAnabolic hormones	Aerobic exercisea Resistance exercisea
Depression	Increased self‐efficacy, masteryInternalised locus of controlDecreased anxietyImproved sleepIncreased self‐esteemIncreased social engagement, decreased isolationDecreased need for drugs associated with depression (beta blockers, alpha blockers, sedative hypnotics)Decreased body fat, improved body image	Aerobic exercise Resistance exercisea
Osteoporotic fracture	Increased bone densityIncreased tensile strengthIncreased muscle massImproved gait stability and balanceImproved nutritional intake (energy, protein, calcium, vitamin D)Reduced fear of falling, improved self‐efficacyIncreased overall activity levels, mobilityDecreased need for drugs associated with postural hypotension, falls, hip fractures (antidepressants, antihypertensives, sedative‐hypnotics)	Resistance exercise Balance exercise
Stroke	Decreased obesityDecreased blood pressureDecreased cholesterol	Aerobic exercise Resistance exercisea
Type 2 diabetes mellitus	Improved insulin sensitivityIncreased GLUT‐4 protein and translocation to membrane sitesReduced visceral fat massDecreased cortisol response to stressImproved dyslipidaemiaDecreased blood pressureIncreased muscle mass	Aerobic exercise Resistance exercise (combined with diet and aerobic exercise)

      ^a Indicates that the modality of exercise has been shown to affect the postulated mechanistic factors but has not yet been shown to prevent the distal disease outcome in epidemiological/clinical studies.

      Evidence for the role of exercise in the treatment of disease

      Mechanisms of benefit

There are many ways to conceptualise the integration of exercise into the treatment of established disease. For example, traditional medical interventions do not typically address disuse syndromes accompanying chronic disease, which may be responsible for much of their associated disability. Exercise is particularly good at targeting syndromes of disuse and may thus significantly impact disability without altering the underlying disease itself in any primary way. Examples include Parkinson’s disease, chronic obstructive pulmonary disease, and chronic renal failure. Exercise may also lower the risk of recurrence of a disease, such as secondary events in patients with cardiovascular disease or preventing recurrent injurious falls in an individual after a hip fracture. Some pathophysiological aberrations central to a disease are specifically addressed by exercise, which may therefore serve as an adjunct to standard care.

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