Contents
Part G Section 3: Metabolic Health1
Introduction 1
Review of the Science 2
Overview of Questions Asked2
Data Sources and Process Used To Answer Questions2
Question 1 Does Physical Activity Have a Role in Preventing or Treating
Metabolic Syndrome?3
Conclusions 3
Introduction 3
Rationale3
Question 2 Does Physical Activity Have a Role in Preventing and Treating
Type 2 Diabetes? 9
Conclusions 9
Introduction 9
Rationale9
Question 3 Does Physical Activity Have a Role in Reducing Macrovascular
Risks in Type 2 Diabetes? 15
Conclusions 15
Rationale16
Question 4 Does Physical Activity Have Benefits for Type 1 Diabetes? 20
Conclusions 20
Rationale20
Question 5 Does Physical Activity Have a Role in Preventing and Treating
Diabetic Microvascular Complications? 22
Conclusions 22
Introduction 23
Rationale23
Question 6: Do Physical Activity and Exercise Have a Role In Preventing
Gestational Diabetes? 28
Conclusions 28
Introduction 28
Rationale28
Overall Summary and Conclusions 29
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Research Needs29
Reference List 30
List of
Figures
Figure G31 Summary of Cross-Sectional Physical Activity and Metabolic Syndrome Studies Using Categories of Physical Activity That Could Be Used To Examine Dose-Response 4
Figure G32 Data Prospectively Demonstrating That Both Higher Levels of Physical Activity and Fitness Protect Against the Future Development of Metabolic Syndrome 5
Figure G33 Summary of Longitudinal Fitness and Metabolic Syndrome Studies That Used Categories of Fitness To Examine DoseResponse Relations 6
Figure G34 Physical Activity/Exercise and Macrovascular Risk Reduction in Type 2 Diabetes19
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Metabolic Health
Introduction
Metabolic syndrome and diabetes are highly significant public health problems in the United States Ford and colleagues 1 estimate, based on government surveys, that 47 million people in the United States have metabolic syndrome It is also estimated that 208 million Americans about 7 of the US population have type 1 diabetes T1D or type 2 diabetes T2D, of whom only two thirds have been diagnosed and the remaining one third are unaware of their condition 2;3 The great majority estimated to be 90 or
more of these individuals have T2D The prevalence of diabetes is higher among persons of Hispanic, African American, and Native American background than among persons of non-Hispanic white origins The majority of deaths in persons with diabetes are caused by cardiovascular disease CVD, including myocardial infarction and stroke People with diabetes not only have a high prevalence of manifestations of atherosclerosis but also have increased prevalence of cardiovascular CV risk factors, including hypertension and the dyslipidemias Alarmingly, type 2 diabetes, once called adult-onset diabetes because it chiefly presented in middle-aged persons, is now appearing in ever younger people, and its prevalence in adolescents and children is increasing rapidly The potential ramifications of T2D in adolescents and children has yet to be determined Exercise and physical activity play a clear role in preventing and treating metabolic syndrome and T2D as well as the macrovascular complications of T2D The importance of the role of exercise and physical activity is highly important and is of increasing interest both in the United States and in other countries as well, as the magnitude of the public
health problems of metabolic syndrome and diabetes continues to increase and as solutions are being sought The role of physical activity and exercise in treating T1D is less well established than for T2D, although evidence suggests that benefits are likely, perhaps most of all in the area of reducing mortality, CVD risk factors, and microvascular complications For both T1D and T2D, physical activity may prevent the development of diabetic neuropathy and diabetic nephropathy Finally, it appears likely that physical activity and exercise may help prevent and treat gestational diabetes although more research is needed to further establish these findings
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Review of the Science
Overview of Questions Asked
This chapter considers 6 major questions dealing with the potential role of physical activity and exercise in preventing and treating metabolic syndrome, T1D and T2D, common complications of diabetes, and gestational diabetes: 1 Does physical activity have a role in preventing or treating metabolic syndrome? 2 Does physical activity have a role in preventing and treating type 2 diabetes? 3
Does physical activity have a role in reducing macrovascular risks in type 2
diabetes?
4 Does physical activity have benefits for type 1 diabetes? 5 Does physical activity have a role in preventing and treating diabetic microvascular complications? 6 Does physical activity and exercise have a role in preventing and treating gestational diabetes?
Data Sources and Process Used To Answer Questions
The Metabolic Health subcommittee used the Physical Activity Guidelines for Americans Scientific Database as its primary source of references for the topics covered in this section of the report see Part F: Scientific Literature Search Methodology, for a full description of the Database The Database contains studies published in 1995 and later In its search, the subcommittee used broad study selection criteria, which included: all age groups; all study designs; all physical activity types as well as cardiorespiratory fitness; disease conditions including T2D, T1D, diabetic nephropathy/neuropathy/retinopathy, metabolic syndrome, gestational diabetes, hypoglycemia, glucose, and insulin Studies were also identified through computerized searches of several databases, including PubMed,
CINAHL, Health Plan, Cochrane Collaboration, and Best Evidence Standard MESH terms often were only partially successful in identifying relevant articles Articles also were found through a combination of searching published reference lists as well as references from meta-analyses and systematic reviews
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Question 1 Does Physical Activity Have a Role in Preventing or Treating Metabolic Syndrome?
Conclusions Regular physical activity is associated with reduced risk of metabolic syndrome Tables G3A1, G3A2, G3A3, and G3A4, which summarize these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ The available data demonstrate an inverse dose-response association between level of activity and risk of metabolic syndrome, with the minimal amount of activity to prevent metabolic syndrome ranging from 120 to 180 minutes per week of moderate-intensity physical activity, and many studies supporting a goal of 150 minutes per week The findings derived from studies using self-report measures of physical activity are similar to those studies in which cardiorespiratory fitness was
measured The dose-response association between physical activity and prevention of metabolic syndrome is similar in men and women Although limited data support the use of exercise for the treatment of metabolic syndrome, this is an area in great need of more work, as is the role of physical activity in preventing and treating metabolic syndrome in youth Table G3A5, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/ report/ and across ethnicities Introduction A number of clinical criteria, such as those of the National Cholesterol Education Program and World Health Organization 4, have been developed to define the metabolic syndrome These criteria are very similar and share the following cluster of characteristics: abnormal levels of lipids low high-density lipoprotein and high triglycerides, elevated glucose, hypertension, and excess abdominal obesity 5-8 This review is not limited to any specific clinical definition of metabolic syndrome but rather includes any report in which the definition of metabolic syndrome was consistent with the above characteristics Rationale In general both cross-sectional and longitudinal cohort studies consistently
show a lower incidence and prevalence, respectively, of metabolic syndrome among physically active individuals as compared with their inactive peers 9-45
Dose-Response Relation
In the cross-sectional studies, which examined the prevalence of metabolic syndrome across levels of physical activity and primarily used questionnaires to obtain self-report data Figure G31, Table G3A3, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/, all found an inverse gradient between amount of physical activity and metabolic syndrome 10;11;13;21;23;26;36
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Figure G31 Summary of Cross-Sectional Physical Activity and Metabolic Syndrome Studies Using Categories of Physical Activity That Could Be Used To Examine Dose-Response
x
Lakka 13 Men Ford 1 Both Carrol 10 Men
Zhu 21 Men Bertrais 23 Men Irwin 11 Women
S Zhu 21 Women z Bertrais 23 Women Halldin 36 Both
12 Odds Ratio of Having Metabolic Syndrome 1 08 06 04 02 0 0 20 40 60 80 100
Level of Self Report Physical Activity
From the cross-sectional studies in which minutes per week of
moderate-intensity physical activity for each category were provided or could be estimated, 120, 150, and 180 minutes or more per week of moderate intensity activity have all been reported as minimum amounts associated with reduced prevalence of metabolic syndrome 13;23;26;36 It should be noted that these studies used different methods of activity assessment, the activity categories have large ranges, and the cut-points for the activity categories were not similar or generated using the same statistical methods None of the studies was designed or powered to analyze the minimal dose of activity to prevent metabolic syndrome However, the cross-sectional data supports that obtaining at least 120 to 180 minutes per week of moderate-intensity physical activity is consistently associated with a lower prevalence of metabolic syndrome Only the 2002 report from Laaksonen and colleagues Figure G32 provides data that could be used to examine the dose-response between physical activity and the development of metabolic syndrome 41
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Figure G32 Data Prospectively Demonstrating That Both Higher
Levels of Physical Activity and Fitness Protect Against the Future Development of Metabolic Syndrome
14 OR for Development of Metabolic Syndrome 12 1 08 06 04 02 0 60 or less 61-180 180 1 2 Fitness Tertiles 3
Minutes of Mod/Vig Leisure Time Physical Activity
Source: Laaksonen et al 41
Figure G32 Data Points
Development of Metabolic Syndrome Odds Ratio Time Physical Activity Low 1 Time Physical Activity Middle 066 Time Physical Activity High 055 Fitness Tertiles Low 1 Fitness Tertiles Middle 059 Fitness Tertiles High 036
The results were similar to those from the cross-sectional studies A dose-response relation exists between level of activity and risk of developing metabolic syndrome, with 180 or more minutes per week of moderate intensity physical activity being the minimal amount of time associated with reduced risk of developing metabolic syndrome
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Physical Activity Level Versus Cardiorespiratory Fitness
Laaksonen and colleagues also measured cardiorespiratory fitness and, as depicted in Figure G32 and Table G3A1, the inverse dose-response relationship associated with
prevention of metabolic syndrome, is even stronger than that seen with questionnaireassessed self-report of physical activity 41 All available prospective studies that measured fitness and categorized participants based on fitness level similarly show a strong inverse dose-response between fitness and risk of developing metabolic syndrome Figure G33 39;41;46-48
Figure G33 Summary of Longitudinal Fitness and Metabolic Syndrome Studies That Used Categories of Fitness To Examine Dose-Response Relations
CARDIA - Both ACLS - Men 12
Risk of Developing Metabolic Syndrome 1
08 06 04 02 0 0 1 2
KIHD - Men ACLS - Women
3
Tertiles of Fitness
CARDIA, Coronary Artery Risk Development in Young Adults; KIHD, Kuopio Ischemic Heart Disease Risk Factor Study; ACLS, Aerobic Center Longitudinal Study
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Thus, despite the methodological differences in assessing physical activity through selfreport questionnaire vs measured cardiorespiratory fitness, the association with the prevention of metabolic syndrome is similar for these two modes of activity assessment
Sex Differences
The available data are
composed of men-only studies, women-only studies, and combinedsex studies, with no one type of study comprising the preponderance of the data As demonstrated in Figure G31, the physical activity-metabolic syndrome association is similar in men and women, indicating that both men and women benefit from participating in regular physical activity As demonstrated in Figure G33, the fitness-metabolic syndrome association also is similar in men and women Thus, no matter whether studies using selfreports of physical activity or objective measures of fitness, it appears that no sex differences exist in regard to the benefits of physical activity in preventing metabolic syndrome
Youth
Only very limited data are available for youth These studies, using a variety of methods to quantify physical activity and define metabolic syndrome, are consistent with the findings in adults, namely that higher levels of activity and fitness are associated with reduced risk of metabolic syndrome Table G3A5, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ 15;44;49;50;50-53 However, this topic is deserving of future study and investigation
Effect of Race and
Ethnicity
The majority of studies with large sample sizes were conducted in Europe or were composed of persons of American or European descent Though some of the better studies were conducted in populations composed of both African Americans and whites, no studies have examined the physical activity-metabolic syndrome association in an African American or Mexican American population only 11;26;46 Thus, the data on the relationship between physical activity or fitness in terms of preventing metabolic syndrome in non-white populations are limited, and this is clearly an area that needs additional research It should be noted that in the studies that used study populations composed of both non-Hispanic whites and African Americans, such as the National Health and Nutrition Examination Survey NHANES and the Coronary Artery Risk Development in Young Adults CARDIA Study, a strong dose-response relation between activity or fitness and prevention of metabolic syndrome was evident 26;46
Prolonged Sitting and Other Sedentary Behaviors
Although regularly participating in physical activity and not leading a sedentary lifestyle may appear to be synonymous, evidence suggests that these two
behaviors should be treated as different dimensions of the same pubic health issue In other words, it is important not only to obtain adequate amounts of aerobic exercise but also to avoid extreme sedentary behaviors, such as prolonged sitting This is obviously of great importance in todays
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environment, in which the typical work day is characterized by long bouts of sitting and most non-work hours are spent watching television Available data suggest a direct relationship between the prevalence of metabolic syndrome and the time spent watching television or using the computer 23;25;26 For example, using NHANES data n1,626 men and women, Ford and colleagues observed that individuals who reported watching television or using the computer 4 or more hours a day had a 2 times greater risk of having metabolic syndrome compared to individuals who reported less than 1 hour a day of television or computer use 26 Given that the current environment in the United States promotes sedentary behavior both within and outside the work place, strategies for reducing sedentary behavior, in addition to
promoting exercise, have great potential public health impact
Role of Physical Activity in Treating Metabolic Syndrome
Numerous studies have examined the benefits of exercise training on individual components of metabolic syndrome, such as blood pressure or fasting glucose In general, improvements to the variables of interest are noted with exercise training However, no published studies have been specifically designed to examine the efficacy of exercise training in the reversal of the clinical diagnosis of metabolic syndrome Two reports have conducted post-hoc analyses to examine the role of exercise in reversing metabolic syndrome Using data from the HERITAGE study, Katzmarzyk and colleagues report that 20 weeks of aerobic training were associated with improvements in triglycerides, blood pressure, fasting glucose, and waist circumference among 105 participants who had metabolic syndrome at baseline 54 Further, the prevalence of metabolic syndrome decreased 305 in this sub-set of participants who received exercise training However, this study was not controlled, which makes the interpretation of this data challenging In a recent manuscript using data from the dose-response
STTRIDE study, Johnson and colleagues observed an improvement in waist circumference, triglycerides, and blood pressure when the included exercise groups walking or jogging exercise in varying intensities n130 were combined None of these variables changed in the control group n41 55 The prevalence of metabolic syndrome also decreased in the combined exercise group from 41 to 27, with no change in prevalence of metabolic syndrome in the control group 39 to 46 Although these preliminary data generated from post hoc analyses suggest that exercise training may be an important therapeutic option for the treatment of metabolic syndrome, this area needs additional research In particular, clinical exercise trials prospectively designed and powered to examine the efficacy of exercise in treating metabolic syndrome are needed
Resistance Training
Very few studies have examined the role of resistance training or quantified muscular strength in preventing or treating metabolic syndrome 56-58 In both a cross-sectional and longitudinal report from the Aerobic Center Longitudinal Database, greater muscular strength was associated with lower risk of metabolic syndrome 56;57 However, in the report
using longitudinal data, the degree of risk reduction associated with greater levels of strength was attenuated from -34 to -24 when cardiorespiratory fitness was adjusted
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for 57 Given the important role of skeletal muscle in insulin sensitivity, developing a better understanding of the role of resistance training in the prevention and treatment of metabolic syndrome is an area of great interest
Question 2 Does Physical Activity Have a Role in Preventing and Treating Type 2 Diabetes?
Conclusions Increased levels of physical activity are associated with significantly decreased risks of developing T2D Most of the studies addressing T2D prevention have focused on vigorous activity, but a number have included walking at moderate intensity, which has proven efficacious as well Importantly, two randomized controlled trials RCTs and results of observational studies provide empiric evidence to support 150 minutes per week of moderate intensity physical activity for T2D prevention Several studies have shown that 30 minutes per day of moderate intensity exercise 5 days per week are effective in
preventing T2D Available data do not enable minimal recommendations, although some of the large observational studies show that any amount of increased physical activity is associated with T2D prevention Recommendations are valid for both men and women Data are insufficient to clearly show that the benefits are uniform across all ethnicities and racial groups but no data support a lack of benefit and available data do support the benefit in these groups Introduction As noted at the beginning of this chapter, diabetes is a highly significant public health problem in the United States Available data reveal that physical activity has a strong role in the prevention and treatment of T2D These data include results from observational studies, and RCTs as well as physiological studies related to physical activity and/or exercise The relationship between T2D and cardiovascular fitness also is important because population studies reveal a direct correlation between all-cause mortality and reduced fitness in persons with T2D 59;60 Following are data that support the importance of physical activity and exercise in the prevention and treatment of T2D as well as a discussion of the safety of
exercise for persons with T2D Rationale
Observational Studies of Physical Activity in Preventing Type 2 Diabetes
Large prospective cohort and cross-sectional observational studies that assessed physical activity through the use of questionnaires all show that increased physical activity levels are associated with reduced risk for developing T2D As with the assessments looking at the relationship between metabolic syndrome and physical activity, it should be noted that these studies used different methods of activity assessment, the activity categories have large ranges, and the cut-points for the activity categories were not generated using the same
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statistical methods In addition, none of the studies was designed or powered to analyze the minimal dose of activity to prevent T2D Importantly though, however the studies were conducted, the benefit of physical activity in preventing T2D is consistently present Major prospective cohort studies are described here to illustrate the range of methods used and results obtained Meta-analyses and structured reviews on this topic are summarized
in Table G3A6, which summarizes these studies and can be accessed at http://wwwhealthgov/paguidelines/report/ These studies reveal that both moderate and vigorous physical activity can prevent T2D Dose-response summary information is provided separately below In a study by Helmrich and colleagues 61 in 5,990 male alumni of the University of Pennsylvania, incidence rates of T2D decreased as energy expenditure in leisure time physical activity in kilocalories per week increased from less than 500 to 3,500 They found that for each 500 kilocalorie increment in leisure-time physical activity, the age-adjusted risk of T2D was reduced by 6 relative risk [RR]094, 95 CI 090-098 61 In a study by Manson and colleagues 62 in the Nurses Health Study cohort 87,252 US women aged 34 to 59 years, the investigators found that women who engaged in vigorous exercise at least once per week had an age-adjusted RR of 067 when compared to women who did not exercise P 00001 This significant benefit persisted even after adjustment for body mass index BMI although results were somewhat attenuated by this measure 62 Hu and colleagues 63 compared the benefits of walking with benefits of vigorous physical
activity on risk of developing T2D in the Nurses Health Study Physical activity was divided into quintiles in this study The authors found that walking considered a moderate intensity form of exercise as well as vigorous activity were associated with decreased risk of T2D, with greater physical activity levels providing the most benefit A study of 5,159 British men revealed a decreased risk for developing T2D that progressively decreased with increasing levels of physical activity 64 Participants were sorted into one of 6 defined levels of physical activity ranging from inactive to vigorously active based on frequency and intensity of the physical activities of each participant The authors found that the age-adjusted relative risk of T2D decreased progressively with increasing levels of physical activity with even moderate physical activity having a significant effect In a study of 6,013 Japanese men, Okada and colleagues 65 found that those who engaged in regular physical exercise at least once a week had a relative risk of T2D of 075 95 CI, 061-093 compared with men not engaging in exercise In a cohort of 34,257 women aged 55 to 69 years, Folsom and colleagues determined that any
level of physical activity was associated with a decreased risk of developing T2D RR069, 95 CI063, 077 when compared with sedentary behavior 66 In a study assessing the effects onT2D of physical activity in 37,918 healthy men where activity levels were classified in metabolic equivalent MET-hours per week and considered either moderate or vigorous, relative risks for T2D across increasing quintiles of MET-hours per week were 100, 078, 065, 058, and 051 P for trend 001 67 Walking pace also was assessed in this study, and walking was found to be efficacious for preventing T2D Hu and colleagues 68 assessed data from 6,898 Finnish men and 7,392 women ranging in age from 35 to 64 years to evaluate the relationship of occupational, commuting, and leisure-time physical activity with the incidence of T2D
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After adjustment for potential confounders, the hazards ratios of diabetes associated with light, moderate, and active work were 100, 070, and 074 respectively P0020 for trend and the authors concluded that high or moderate levels of activity were associated with a reduced risk of T2D 68 In a
prospective cohort study of 37,878 women, a participant was considered active if she expended more than 1,000 kilocalories on recreational activities per week, with activity levels being divided into quartiles 69 Physical activity was an independent predictor of T2D in this study although BMI was a more powerful predictor In the Womens Health Initiative Observational Study, Hsia and colleagues 70 found that physical activity across exercise quintiles was associated with a decreased risk of T2D particularly in non-Hispanic white women This was true for walking multivariate-adjusted hazard ratios 100, 085, 087, 075, 074; P for trend 0001 across exercise quintiles and total physical activity score hazard ratios 100, 088, 074, 080, 067; P0002 These data demonstrate a strong inverse relationship of physical activity across quintiles with diabetes risk in non-Hispanic white women and men Associations in women of other races and ethnicites are less clear, but the authors of one study 70 note that the study may not have been adequately powered to fully assess data from particular race or ethnic subgroups or possibly that physical activity levels among these groups may not have been intense
enough to allow for analyses see section below
Physical Activity Level Versus Cardiorespiratory Fitness
Similar to the questionnaire studies, observational studies that assessed physical activity levels using objective measures of cardiorespiratory fitness reported that better fitness is associated with a reduced risk of developing T2D 71-73 Lynch and colleagues 71 found that in a population-based sample of 897 middle-aged Finnish men, higher cardiorespiratory fitness was associated with lower risk of developing T2D compared to sedentary persons Wei and colleagues 60;72 found that low cardiorespiratory fitness measured during a maximal exercise test and physical inactivity measured by self-report were associated with risk of impaired fasting glucose and T2D as well as all-cause mortality in men with T2D In the former study, after adjusting for potential confounders, men in the low-fitness group the least fit 20 of the cohort at baseline had a 19-fold risk 95 CI, 15- to 24fold of impaired fasting glucose and a 37-fold risk CI, 24- to 58-fold of T2D compared with those in the high-fitness group In another study, in which cardiorespiratory fitness was measured during an exercise test
and the 6,249 female participants were divided into thirds by level of fitness, Sui and colleagues 73 found that compared with the least fit third, the adjusted hazard ratio was 086 95 CI059-125 for the middle third and 061 95 CI038-096 for the upper third of cardiorespiratory fitness Similar to results from studies using self-report data, results from these studies overall suggest a benefit for achieving and maintaining increased levels of physical activity 64;66;74;75
Randomized Controlled Trials of Type 2 Diabetes Prevention
The difficulty of evaluating many of the large RCTs looking at the effects of physical activity or exercise on diabetes prevention has been to sort out the effects of diet versus physical activity, as these treatments are commonly combined in large trials Three large
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RCTs have assessed the role of physical activity independently, either using trial design or by analytic means Table G3A7, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ The Da Qing Impaired Glucose Tolerance and Diabetes Study in China 76 included an
exercise-only treatment arm and found that even modest changes in exercise, without change in diet, reduced the risk of developing diabetes The exercise prescription in this study was 1 or 2 units of exercise a day, with units defined in terms of intensity and duration One unit was equal to 20 minutes of mild exercise eg, slow walking, shopping, housekeeping, 20 minutes of moderate exercise eg, fast walking, cycling, or 10 minutes of strenuous exercise eg, slow running, stair climbing or 5 minutes of very strenuous exercise eg, skipping, basketball In this trial, which was randomized by clinic rather than by participant, diabetes risk was reduced 46 in the exercise group, 42 in the diet and exercise group, and 31 in the diet-treated group The Diabetes Prevention Study in Finland 77;78 and the Diabetes Prevention Program in the United States 79 have provided clear evidence that intensive lifestyle modifications, including strong diet and physical activity interventions, reduce the risk of developing T2D Importantly, the role of physical activity is independently beneficial to preventing diabetes In the Diabetes Prevention Study, 522 middle-aged, overweight men and women with
impaired glucose tolerance IGT were randomized to either lifestyle modification or a control group 77;78 The physical activity prescription portion of the lifestyle modification which included a strong dietary component was for 30 minutes a day of moderate exercise for a total of more than 4 hours per week Incidence of diabetes was very significantly reduced in the intervention group In the Diabetes Prevention Program, 3,234 men and women with IGT and impaired fasting glucose were randomized into control, medication ie, metformin, a drug commonly used to treat T2D, or lifestyle modification groups The physical activity prescription portion of the lifestyle arm which also had a strong dietary component was 150 minutes of activity per week The lifestyle component reduced incident diabetes by 58 and had a more powerful effect than metformin by 39 In the Diabetes Prevention Program and Diabetes Prevention Study, weight loss was the dominant predictor of a reduced incidence of diabetes However, recent analyses from these studies showed that increased levels of physical activity prevented diabetes even after adjusting for confounders 80-82
Physiological Data Showing Benefits of Exercise
in Treating Type 2 Diabetes and Elucidating the Role of Cardiorespiratory Fitness
Type 2 Diabetes is associated with reduced exercise capacity 83;84 Maximal oxygen consumption was approximately 20 lower compared to nondiabetic persons of similar weight and physical activity levels in these studies These exercise abnormalities are present even in the absence of diabetes-related complications and even in persons with recently diagnosed T2D The abnormalities are likely associated with cardiac and hemodynamic abnormalities 85-87
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It has been well established that a single bout of moderate exercise has a profound effect on glucose metabolism that may last up to about 18 hours 88 In addition, repeated bouts of exercise appear to have a cumulative beneficial effect on glucose metabolism A metaanalysis 89 including 14 studies, provides evidence that regular moderate-intensity exercise improves metabolic control in T2D This meta-analysis shows that exercise significantly improves glycemic control and reduces visceral adipose tissue and plasma triglycerides, although not plasma cholesterol, in
people with T2D, even in the absence of weight loss Exercise training in persons with T2D also has a very significant effect in terms of improving maximal oxygen consumption, measures of submaximal exercise performance, and other measures of fitness eg, 90;91 Available data suggest that these findings are true for African American women 92 as well as white women These findings are further discussed in the section on preventing macrovascular complications of T2D
Dose-Response Relation
Data on exactly how much physical activity is needed in order to prevent T2D are limited because such studies have not been prospectively designed Data from observational studies indicate that the amounts of effective physical activity range from any increase over sedentary levels to moderate and vigorous activity levels It appears, therefore, that any physical activity may be better than none in terms of preventing diabetes, but better results are achieved if individuals engage in higher intensity and more frequent physical activity Data from several studies support that approximately 30 minutes of moderate intensity exercise at least 5 days per week provides a substantial 25 to 36 reduction in the
risk of T2D according to the Nurses Health Study 63, the Iowa Womens Health Study 66, the Study of Eastern Finns 68, and the Diabetes Prevention Program 79 Importantly, several of the prospective cohort studies discussed above included walking as a specific modality of physical activity and all of these found that walking was beneficial in terms of preventing T2D compared to sedentary behavior 61;63;67;69;70 Thus, data from observational studies and RCTs support the current recommendation that 25 hours per week or typically 30 minutes a day for 5 days a week be performed to prevent T2D Jeon and colleagues 75 performed a meta-analysis on the prospective cohort studies that assessed the preventive effects of moderate-intensity physical activity that could be analyzed independent of vigorous-intensity physical activity Moderate-intensity physical activity was defined as an activity requiring 30 to 60 METs 75 They identified 10 cohort studies that met these criteria These studies in total included 301,121 participants and 9,367 incident cases Five of the studies specifically included walking The summary RR of T2D was 069 95 CI 058-083 among participants who regularly participated in
moderate-intensity exercise compared to sedentary counterparts The RR for T2D was 070 058-084 for walking on a regular basis typically briskly for 25 hours per week or more compared to no walking However, no data are available to support a specific recommendation for a minimal or even a lesser dose of exercise In addition, it is not clear how much additional risk reduction is obtained with higher levels of physical activity
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Sex and Race/Ethnicity Differences
In observational studies that included women only, 3 large US cohort studies 67-70 all found that greater physical activity was associated with a lower incidence of diabetes However, in one study, this relationship was present only in non-Hispanic white women and not in women of African American, Hispanic or Asian descent 70 These findings await confirmation in further studies because the study may not have been powered to detect differences across all race or ethnic groups Results were based on self report of diabetes in the total population but were confirmed in a subset who also provided blood samples and physician reports
Data from RCTs as well as observational studies suggest clearly that overall, increased levels of physical activity play a beneficial role in preventing T2D for both women and men In the Diabetes Prevention Program 93, treatment effects did not differ significantly according to sex, race, or ethnic group Lifestyle factors addressed in the Program included diet and physical activity, and both had an independent effect on preventing T2D Although participant numbers became too small for clear results when grouped by ethnicity, it appears that risk reduction compared with placebo was greater for the lifestyle group than for the metformin group in non-Hispanic whites 50 versus 12, respectively and Hispanics 57 versus 2, respectively 94 African Americans 42 versus 29 and Native Americans 43 versus 42, showed similar efficacy for the lifestyle and metformin groups However, for Asian Americans, metformin showed a nonsignificantly greater reduction than intensive lifestyle intervention 62 versus 30 Neither lifestyle nor metformin showed significant heterogeneity across the 5 ethnic groups in terms of efficacy Subsequent studies in India and Japan 95;96, as well as the Da Qing study in
Chinese people 76, similarly found an independent effect of physical activity in preventing T2D, and the findings were true for men and women and appeared to be true for all ethnic groups involved Thus, overall, acknowledging the limited data available to date, no strong evidence is available to negate the data suggesting that physical activity prevents T2D in men and women of different race and ethnic groups, although further research should explore this important issue
Youth
Type 2 Diabetes is growing in prevalence in children and adolescents Alarmingly, unlike youth who do not have T2D, youth with this condition often have CV risk factors, such as hypertension and dyslipidemias as well Thus, potentially, youth who have T2D may develop CVD at relatively young ages 97;98 Data from RCTs show that increased physical activity improves insulin sensitivity in obese youth, although longitudinal data are limited 99-101 and the effects on CV risk factors are not well established because trials are lacking A recent review has highlighted the efforts of different interventions to address obesity in youth of various ethnic and racial groups These interventions focused on lifestyle changes
including increased physical activity 102, and several had a physical activity-only component 103;104 Overall findings were encouraging The studies of both Sallis and
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colleagues 103 and Pangrazi and colleagues 104 showed that school-based programs promoting increased physical activity were effective at increasing the physical activity level or cardiorespiratory endurance although not in reducing BMI of girls especially No RCTs have been completed that show that physical activity or exercise prevents T2D in youth although it is likely give results in aduls To date, the limited intervention and observation studies suggest that to prevent and manage T2D, daily goals for youth should include less than 60 minutes of daily screen television, computer or video game time and 60 to 90 minutes of daily physical activity 105-107 A large multicenter trial the TODAY study is currently underway to assess the role of physical activity in preventing T2D in youth 108
Resistance Training
Resistance training has shown promise as a modality for treating diabetes 109;110 Sigal and colleagues 111 found,
in a group of 251 individuals with T2D, that both aerobic and resistance training individually improved glycemic control, but improvements were greatest with combined aerobic and resistance training However, this exercise modality has not been explored for its role in prevention of T2D in large trials, and no data currently exist showing that resistance training plays a role in preventing T2D Future studies should further investigate the role of resistance training in preventing T2D given the beneficial effects of such training on the metabolism of persons with T2D
Safety of Physical Activity and Exercise for Persons With Type 2 Diabetes
The consensus is that the benefits of exercise for persons with T2D far outweigh the risks However, safety concerns about exercise in this group have been voiced These concerns range from cardiovascular risks associated with physical activity and exercise to caution about hypoglycemia and foot care concerns The American Diabetes Association ADA guidelines on safety 112;113 provide a comprehensive review of safety issues and measures, although the recommendations lack supporting data in some cases
Question 3 Does Physical Activity Have a Role in
Reducing Macrovascular Risks in Type 2 Diabetes?
Conclusions Strong data support the benefits of physical activity and fitness for CVD protection in T2D and IGT The data are stronger for hard outcomes, such as CVD events and mortality, than for known CVD risk factors, but this may be an artifact of the relatively short duration of risk factor studies and the potential for small changes in risk factors to have a large cumulative impact on outcomes These data suggest that a minimum of moderate-intensity aerobic activity for more than 2 hours per week is necessary to achieve significant benefit, and that near maximum benefit may be achieved with moderately vigorous aerobic activity, such as brisk to very brisk walking, for 3 to 7 hours per week about 12 to 21 MET-hours per week Combined aerobic and resistance activity appears to have greater benefits than
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either type alone when CVD risk factors and non-CV effects are considered, but CVD outcome data for activity other than aerobic activity are lacking In general, the existing data for CVD risk reduction in persons with T2D are consistent
with a recommendation of an aerobic activity program with a goal of at least 120 minutes per week and preferably more than 180 minutes per week of moderate to moderately vigorous activity Rationale Several studies have specifically considered the effects of physical activity on CVD risk factors and outcomes in T2D Observational studies have shown that, among persons with this condition, those who exercise or are more fit have a reduced risk of CV morbidity and mortality than do less active or less fit individuals 67;114-118 Tables G3A8 and G3A9, which summarize these studies, can be accessed at http://wwwhealthgov/paguidelines/ report/ A study of more than 3,000 Finns with T2D found that all types of physical activity eg, recreational and occupational are beneficial in reducing CV events and mortality 117 Following is a review of the evidence for benefits, dosage, and type of physical activity specifically for reduction of CVD risk and outcomes in T2D
Cardiovascular Disease Risk Factor Reduction
Many cross-sectional studies have found inverse correlations between physical activity level and various CVD risk factors in T2D populations Two meta-analyses of these studies have been
performed 119;120 One focused on lipid effects and hemoglobin A1c HbA1c and found a small 5 but significant decrease in low-density lipoprotein LDL cholesterol -64 mg/dl, range -118 to -11 and a strong trend toward improved HbA1c -04, range -08 to 00, but no change in total cholesterol or triglycerides 120 This section focuses on a recent meta-analysis of controlled intervention studies in subjects with T2D that compared different exercise interventions for their effects on CVD risk factors 119 The meta-analysis covers about 1,000 subjects, aged 48-62 years Exercise interventions were of aerobic, resistance, or combined types Overall conclusions from the analysis were that all forms of exercise improved insulin sensitivity, with combined types having the greatest effect especially in men and resistance alone the least Combined exercise also had small and moderate benefits on systolic and diastolic blood pressure, respectively, and a small benefit on raising high-density lipoprotein HDL levels Aerobic exercise also benefited triglyceride levels and systolic blood pressure Resistance exercise did not show significant benefit on any CVD risk factor Another recent prospective trial
with a 6-month, twice weekly, progressive, supervised aerobic program in a population with T2D also demonstrated improved HDL levels 12 and marked decreases in markers of endothelial dysfunction ICAM-1 and P-selectin, but no changes in inflammatory markers hsCRP and TNF-alpha or LDL levels 121
Cardiovascular Disease Outcomes
Only one intervention study and no randomized trials have addressed the effect of activity or fitness on hard CVD outcomes The ongoing Look AHEAD Action for HEAlth in Diabetes trial, currently underway, is a randomized long-term study addressing hard CV
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outcomes after an intervention 122-124 However, the intervention is targeted at weight loss by a combined program of diet and physical activity and thus will not address the effect of physical activity in isolation In the one existing interventional trial looking at physical activity alone, Shinji and colleagues followed a small group n102 of T2D adults for 17 months after institution of a single, modest, home-based exercise program walking 20 to 30 minutes, 4 to 6 times per week, at anaerobic threshold 125
Incident CVD was much higher in dropouts than in completers even after adjustment for multiple parameters with a RR for incident CVD of 165 95CI, 119-228 for dropouts versus completers This study suggests that low-level physical activity is beneficial for primary CVD prevention in people with T2D However, no data were reported or adjustments made for smoking or diet, the dropouts versus completers study comparison was nonrandomized, the number of events was very small n8, and the confidence interval was very large Several prospective cohort studies have found that CV fitness 60;126-128 Table G3A8 and physical activity level 60;67;115-118;129;130 Table G3A9 are inversely correlated with mortality all-cause and CVD and/or CVD event rates in subjects with T2D Some of these studies have evaluated the effect of frequency, duration, and/or intensity of physical activity on the protective effect A follow-up of the National Health Interview Survey of 2,896 adults with T2D 115 found that walking for more than 2 hours per week but not more than 0 hours to 19 hours was associated with a significantly decreased hazard ratio HR for CVD mortality HR 059, 95 CI 040 to 087, P for trend 003 after
exclusion of disabled subjects, and after adjusting for age, sex, race, BMI, self-rated health, smoking, weight loss approaches, hospitalizations, hypertension or medications, physician visits, limitations caused by CVD or cancer, and extent of functional limitation In the Nurses Health Study of more than 5,000 diabetic women followed for 14 years, subjects were placed in 5 groups based on hours of total moderate-vigorous activity per week, including non-leisure activities 67 RR for CVD events fatal and nonfatal myocardial infarction or stroke decreased progressively with increasing weekly volume of moderate to vigorous activity less than 1, 1 to 19, 2 to 39, 4 to 69, and 7 or more hours per week Age-adjusted relative risks were 10, 093 95 CI, 069 to 126, 082 95 CI, 061 to 110, 054 95 CI, 039 to 076, and 052 95 CI, 025 to 109 P for trend 0001 This relationship did not change appreciably after adjustment for smoking, BMI, and other CV risk factors Among women who primarily walked for exercise, both increased pace easy pace: 10, average pace: 052, brisk pace: 047, P for trend 0001 and weekly MET walking score were inversely associated with CVD event risk Among women who did not
exercise vigorously in addition to walking, multivariate relative risks across quartiles of MET scores for walking were 10, 085 062-134, 063 036-110, 056 031-100 P for trend 003 for 0 to 05, 06 to 27, 28 to 75, and more than 75 MET hours per week of walking In the Health Professionals follow-up study, Tanasescu and colleagues followed about 2,800 men with T2D for 14 years and assessed incident CVD fatal or nonfatal MI or stroke 116 Risk of total and fatal CVD events showed a statistically significant improvement
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with increasing physical activity after age-adjustment P for trend 002, 003, respectively and a strong trend after multivariate analysis adjusted for alcohol intake; smoking; family history of myocardial infarction; use of vitamin E supplements; duration of T2D; diabetes medication; quintiles of dietary intake of trans fat, saturated fat, fiber, and folate; history of angina and coronary artery bypass graft; and baseline presence of hypertension and high serum cholesterol; P for trend 007, 013, respectively Additional adjustment for BMI further attenuated the trend for total
CVD events: 10, 091 [063-131], 068 [045-102], 076 [051-114], and 072 [047-109] by quintile; P for trend 014 Their results suggest that physical activity protects from CVD events, especially fatal events, and that for T2D, moderate energy expenditure 3rd quintile, 12 to 22 MET-hours per week, corresponding to about 3 to 5 hours per week of brisk walking provides the most protection The authors state that this was not the case in the non-diabetic cohort where a more continuous doseresponse was seen A separate walking intensity multivariate analysis suggests that for those who walked for exercise, the higher the walking speed, the greater the protection After adjustment for CVD risk factors, walking time, and other vigorous activity, the relative risks for normal pace 2 to 29 miles per hour, brisk pace 3 to 39 miles per hour, and very brisk pace more than 4 miles per hour were 082, 058, and 017 95 CI 004 to 071; P for trend 0001 compared to an easy pace less than 2 miles per hour The studies described above suggest that maximum benefit may be achieved with substantial volumes of moderately vigorous exercise, such as brisk to very brisk walking, for 3 to 7 hours per week It is
interesting to speculate that subjects with T2D may differ from nondiabetic subjects in their response to very vigorous exercise, but further studies are needed to fully address the intensity response of CVD risk reduction with physical activity in T2D In the Whitehall Study, Batty and colleagues performed a comparative study of the benefits of physical activity in men with T2D or IGT Table G3A9 compared to men with normal glucose tolerance 131 After adjustment for other factors, physical activity remained an independent predictor of all-cause, CHD, and other CVD mortality The gradient for benefit with increasing physical activity was much steeper for the IGT/T2D subjects than for those with normal glucose tolerance, suggesting a greater benefit for metabolically impaired subjects than for the general population A plot adapted from this data illustrates that the highest level of physical activity actually eliminated the excess CHD mortality associated with IGT and T2D 132 Figure G34 Others have also found a steeper response of CVD risk to physical activity in diabetic subjects, but most studies have found that CVD risk remains greater in diabetic than nondiabetic subjects even in
the most active subgroups 116
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Figure G34 Physical Activity/Exercise and Macrovascular Risk Reduction in Type 2 Diabetes
Note: Age-adjusted cardiovascular disease mortality rates by leisure time activity in normoglycemic men n6,056 versus men with impaired glucose tolerance/diabetes n352 in the Whitehall Study Adapted by Gill and Malakova 2006, 132 from data from the Whitehall Study P0006 for trend in normoglycemic men, P0003 for trend in men with IGT/diabetes Source: Gill JM, Malkova D Physical activity, fitness and cardiovascular disease risk in adults: interactions with insulin resistance and obesity Clin Sci Lond 2006 Apr;1104:409-425 Review Reproduced with permission
Physical Activity, Cardiovascular Fitness, and Type 2 Diabetes
A recent meta-analysis evaluated the benefits of physical activity for CV fitness in persons with T2D 133 The overall analysis of 9 randomized, controlled, prospective interventional studies had mean exercise characteristics of 34 sessions per week and 49 minutes per session for 20 weeks Mean baseline maximal oxygen consumption of 224 ml/kg/min
increased 118 in the exercise arms and decreased 10 in the control arms Magnitude of improvement in maximal oxygen consumption and in HbA1c correlated better with exercise intensity than with exercise volume Because fitness and glycemic control appear to benefit overall and CVD mortality, this suggests that more intense exercise would have greater mortality benefits However, the possibility of a mortality impact of intense exercise in diabetic people cannot be ruled out and is, in fact, suggested by some outcome studies discussed above Furthermore, overt nephropathy, peripheral neuropathy, and retinopathy present in many diabetic individuals may be contraindications to very vigorous activity, prolonged stepping activities, and weight-lifting or high-impact activities, respectively,
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though these recommendations appear to be based on little experimental evidence see Question 5 Does Physical Activity Have a Role in Preventing and Treating Diabetic Microvascular Complications?
Question 4 Does Physical Activity Have Benefits for Type 1 Diabetes?
Conclusions Data are more limited for type
1 diabetes T1D than for T2D, but generally support benefits of exercise for T1D in reducing mortality, CVD risk factors, and microvascular complications Data are weaker for benefits for glycemic control, and CVD outcomes have not been studied Data regarding the optimal exercise prescription also are limited This may still include limiting exercise appropriately in proliferative retinopathy However, any exercise prescription in T1D also must address the issue of avoiding exercise-induced hypoglycemia This requires an individualized approach that includes modifying insulin dosing, ingesting additional carbohydrates, and ensuring appropriate details of the exercise prescription Rationale Though T1D is less prevalent than T2D, it remains among the most prevalent chronic, serious diseases of childhood affecting about 15/1,000 children in the United States 134 Overall prevalence estimates are increasing now that it has been recognized that a quarter to a half of all T1D develops in adults Although the metabolic abnormalities associated with insulin resistance have not been considered major factors in this autoimmune form of diabetes, CVD has long been known to be a major cause of
morbidity and mortality in T1D It is now becoming recognized that insulin resistance is also present in T1D and that this may contribute to the associated excess CVD risk As T1D individuals spend a longer portion of their lives with absolute endogenous insulin deficiency and relative insulin sensitivity, hypoglycemia is a greater safety concern in T1D than in T2D Effects of physical activity on CVD risk factors and glycemic control and safety concerns are addressed in this section Microvascular complication effects are addressed in a later section see Question 5 Does Physical Activity Have a Role in Preventing and Treating Diabetic Microvascular Complications? As with T2D and non-diabetic populations, exercise has been shown to be inversely correlated with mortality in T1D In a cohort study of 548 T1D subjects followed for 7 years in the Pittsburgh Insulin-dependent Diabetes Morbidity and Mortality Study, sedentary males were 3 times as likely to die as active males 135 The relationship did not achieve statistical significance in women
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Physical Activity and Type 1 Diabetes
Prevention
No data exist to show that habitual physical activity or exercise plays a role in preventing T1D
Physical Activity and Type 1 Diabetes Treatment
Glycemic Control Exercise increases insulin sensitivity and induces non-insulin dependent skeletal muscle glucose uptake Overweight or otherwise insulin resistant T1D individuals will derive benefit from the improvement in insulin sensitivity that accompanies exercise in the same way that T2D individuals do see Question 1 Does Physical Activity Have a role in Preventing or Treating Metabolic Syndrome? Recent evidence suggests that even apparently insulin sensitive diabetic individuals are insulin resistant compared to nondiabetic controls 136;137 Theoretically, therefore, most or all T1D patients might be expected to improve insulin sensitivity with physical activity As such, it would seem that exercise could improve glycemic control However, for a T1D patient on a regular dose of insulin, this improved sensitivity comes at the cost of an increased risk of hypoglycemia and resultant hyperglycemia Furthermore, high-intensity exercise increases catecholamine release and can cause post-exercise hyperglycemia Thus, studies have
had mixed results Nevertheless, the largest studies have demonstrated improved glycemic control with physical activity in T1D Interventional studies, most from the 1980s, have all been small Table G3A10, which summarizes these studies, can be accessed at http://wwwhealthgov/ paguidelines/report/ Most have used a moderate aerobic exercise program and have had mixed results, with some negative 138-144 and some modestly positive 145-148 trials One of the positive trials included a carbohydrate control diet intervention in addition to exercise 145 Thus, the improved glycemic control in this study cannot clearly be attributed to exercise Other positive studies did not include any dietary change or monitoring Some negative trials followed caloric intake and noted an increase in calories in the exercise group 139 Few studies have looked at resistance training Two studies with resistance interventions were split, one with improvement in HbA1c 148, the other without 143 Larger cross-sectional studies have also been split Table G3A11, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ Ligtenberg studied 200 subjects and found no correlation between
self-reported activity and HbA1c 149 The FinnDiane study of 1,030 T1D subjects found a sex-based difference in that selfreported physical activity did correlate with improved HbA1c in women, but not in men 150 The effect on HbA1c in women was an 05 decrease in both the moderately active 10 to 40 MET-hours per week and active groups more than 40 MET-hours per week In contrast, in men, insulin doses were decreased to a greater extent in the more active populations In the largest study to date, Herbst and colleagues studied more than 23,000 subjects with T1D and found a small, but highly significant improvement in HbA1c 03 in the 2 active groups exercise 1 to 2 times a week and 3 or more times a week compared to the sedentary group 151 Only one study compared resistance to aerobic training and found no benefit for glycemic control in either arm 143 Overall, good evidence for a significant role for exercise alone in glycemic control is limited Existing evidence suggests
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that a modest improvement in glycemic control occurs with small amounts of activity and does not increase with more
frequent or more intense exercise More studies are needed to further clarify the role of physical activity in T1D because many of the studies are relatively old Macrovascular Complications CVD risk factors The FinnDiane study found that low physical activity correlated with the presence of metabolic syndrome in TID, especially the waist circumference component 152 Lehman and colleagues found significant improvements in insulin sensitivity, LDL, HDL, blood pressure, and waist-to-hip ratio with a self-monitored increase in physical activity of about 150 minutes per week without an increase in severe hypoglycemic events 153 Few studies have investigated the effect of different doses or types of exercise on CVD risk factors in TID In one 12-week intervention study, Ramalho and colleagues compared the effects of thrice weekly 40 minutes of moderate aerobic training to resistance training 143 Neither group improved lipid profiles, but the aerobic group had improved waist circumference while the resistance group did not CVD outcomes No data exist on the effect of physical activity on actual CV outcomes specifically in T1D
Physical Activity, Type 1 Diabetes, and Risk of
Hypoglycemia
Whatever the benefits of exercise in T1D, it is clear that they come at the expense of an increased risk of hypoglycemia, both during and up to 30 hours after exercise However, the ADA Position Statement on Physical Activity and Exercise states the all levels of physical activity, including leisure activities, recreational sports, and competitive professional performance, can be performed by people with T1D who do not have complications and are in good glucose control154, p61 This is because it is possible, with a good understanding of the physiologic responses to exercise, to manage exercise and postexercise blood sugars Guidelines for hypoglycemia control have been published, although they are not always strongly data-based and therefore are outside the scope of this section 155-162
Question 5 Does Physical Activity Have a Role in Preventing and Treating Diabetic Microvascular Complications?
Conclusions Physical activity may prevent the development of diabetic neuropathy and diabetic nephropathy primary prevention in those with T1D and T2D Though uncontrolled observational studies suggest physical activity may treat diabetic neuropathy and nephropathy, RCTs are
necessary to confirm this Other observational studies suggest no effect of physical activity on either the prevention or treatment of diabetic retinopathy in T1D subjects No data are available on sex differences or dose-response of physical activity
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Moderate-intensity physical activity appears safe for all individuals with diabetes even those with existing diabetic microvascular complications, although vigorous-intensity activity, high-impact exercise, or weight-bearing exercise may possibly lead to adverse outcomes in those with existing proliferative retinopathy, severe nephropathy with renal osteodystrophy, or severe neuropathy, respectively Exercise stress testing is not recommended before starting a moderate-intensity exercise regimen and is of controversial benefit before initiating a vigorous intensity aerobic exercise program Introduction Persons with diabetes have a highly increased prevalence of microvascular complications, which are associated with substantial morbidity In this section, the role of physical activity in preventing and treating microvascular complications in
those with T1D and T2D will be discussed For the purpose of this document, microvascular complications of diabetes are defined to include neuropathy based either on symptoms, physical examination, or abnormal electromyogram findings consistent with this diagnosis, nephropathy defined as microalbuminuria, macroalbuminuria, or decreased calculated glomerular filtration rate, and retinopathy defined as non-proliferative or proliferative retinopathy diagnosed by an ophthalmologist using retinal photographs To date, no large RCTs have investigated the role of exercise training or physical activity in preventing or treating diabetic microvascular complications One small RCT and some observational studies have suggested a possible relationship between physical activity and both the primary prevention and treatment tertiary prevention of diabetic microvascular complications One meta-analysis 119 has evaluated the impact of physical activity on a surrogate intermediate marker HbA1c for progression to diabetic microvascular complications, and showed convincingly that physical activity interventions lower HbA1c Because better glycemic control has been shown to decrease the incidence of
diabetic microvascular complications in subjects with T1D 163 and T2D 164, it is possible that exercise training could reduce microvascular complications solely due to its general improvement of glycemic control However, the overall lack of studies in this area means that the role of physical activity in preventing microvascular complications remains inconclusive Specific gaps in the literature that warrant further research are large studies to determine the exercise dose-response curve for prevention or treatment of microvascular complications, and determining whether differences exist by subject race/ethnicity, sex, T1D vs T2D, or exercise modality The next three sections will summarize what is known regarding the role of physical activity in preventing and treating 1 diabetic neuropathy, 2 diabetic nephropathy, and 3 diabetic retinopathy Safety concerns for exercise in these populations also will be discussed Rationale Observational studies provide most of the existing data, which are of limited scope and quality, to determine the role of physical activity in primary prevention of diabetic
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nephropathy, neuropathy, and retinopathy Observational studies of lesser quality often uncontrolled have been performed to address the role of physical activity for treatment of diabetic nephropathy, neuropathy, and retinopathy To determine the safety of physical activity with existing microvascular complications, small observational studies have been performed and clinical standards of care also have been discussed when appropriate to supplement the scarce amount of safety data
Diabetic Neuropathy
One small RCT 165, one cross-sectional study 166, and one retrospective cohort study 167 have evaluated the impact of physical activity on primary prevention of diabetic neuropathy Table G3A12, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ From these limited data, no firm conclusions may be drawn but it does appear that physical activity may possibly have some role in preventing diabetic neuropathy The RCT data, although only based on 78 participants 73 with T2D, revealed a reduction in both motor and sensory neuropathy from 4 years of moderate-intensity exercise despite no significant weight loss 165 Of the 2 cross-sectional studies
performed in T1D subjects addressing neuropathy, one showed physical activity significantly benefited males only 166, while the other had no effect 167 Treatment of Diabetic Neuropathy No studies have evaluated the use of physical activity to treat diabetic neuropathy One study evaluated 12 months of physical activity in conjunction with a dietary intervention for prediabetic neuropathy Table G3A13, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/, using a pre-post study design in 40 subjects with prediabetes to show significant differences in nerve fiber density at the proximal portion of the leg P 005, and non-significant improvement in neuropathic pain and nerve fiber density at the distal portion of the leg 168 With respect to diabetic ulcer prevention in a group with diabetic neuropathy, no significant improvement in the surrogate outcome of dorsal foot cutaneous perfusion was found after either a 10-week aerobic exercise 169 or 8-week resistance exercise program 170 Although significant differences were initially described in dorsal foot cutaneous perfusion between physically active individuals with T2D as compared with sedentary
individuals with T2D who had a higher mean HbA1c 171, no differences were evident when this study was repeated with similar HbA1c levels between groups 172 This area requires further study Safety of Exercise With Diabetic Neuropathy Three different aspects of safety of exercise with comorbid neuropathy are at issue: 1 Safety of exercise with autonomic neuropathy, 2 Ulcer risk with existing neuropathy, 3 Fall risk with existing neuropathy
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Safety of exercise with autonomic neuropathy Existing guidelines are not based on data and are therefore are outside the scope of this chapter Graham and Lasko-McCarthy and Sigal and colleagues provide further information on this topic 112;173 Ulcer risk with existing neuropathy Two studies observed an inverse relationship between physical activity and ulcer incidence 174;175 However, 2 other studies have suggested that abrupt increases in activity may increase the short-term risk of ulceration Armstrong and colleagues found a significantly greater coefficient of variation in the group with recurrent ulcer 174 and Lemaster and colleagues 175 found a
significant unadjusted increased risk of ulcer with increased short-term activity Ulcer risk was increased with greater intensity and duration of loading pressure on the feet while walking 176;177 possibly showing a clinical benefit to protective diabetic footwear in this population Risk of falls with existing neuropathy Several studies have evaluated the degree to which gait is altered by diabetic neuropathy suggesting attendant increased fall risk, with one study showing a targeted intervention may improve balance in this population Dingwell and colleagues as well as other researchers have performed studies showing decreased walking speeds or decreased gait variability 176;178-180 in those with diabetic peripheral neuropathy versus non-diabetic controls Giacomozzi and colleagues also showed those with diabetic neuropathy and a prior foot ulcer had even greater gait variability than those with neuropathy and no prior ulcer 176 Mueller and colleagues showed that the peak torque generated during plantar flexion and the range of motion of dorsiflexion at the ankle are strongly correlated r 078 and contribute to the power generated from the ankle joint during ambulation 181 These
data suggest that decreased ankle dorsiflexion range of motion and/or plantar flexion strength are associated with decreased step length and speed during walking 181 Novak and colleagues 182 reported that 30 individuals with T2D and associated diabetic neuropathy described worse foot pain and walked shorter distances than subjects with T2D without neuropathy and non-diabetic controls, with strong correlation between pain level and walking distance r -045, P 0001 182 The data presented here generally support the pragmatic exercise precautions recommended in clinical practice guidelines Table G3A14, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ Those with severe peripheral neuropathy should use non-weight bearing activities to avoid foot ulceration or Charcot joint destruction 112;173, and all individuals with diabetes should use appropriate footwear and inspect their feet daily to reduce injury risk 183
Diabetic Nephropathy
Four cross-sectional studies 150;152;166;184 and 1 retrospective cohort study 167 have evaluated the impact of physical activity on diabetic nephropathy prevention in subjects with T1D Table G3A12 These data are not
available in patients with T2D From these limited data, no firm conclusions may be drawn but they suggest physical activity may prevent diabetic nephropathy In 2 separate cross-sectional analyses of slightly different subsets of a Finnish population with T1D, less physical activity was associated with greater prevalence
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of nephropathy 150;152 A significant association was observed between greater leisuretime physical activity and decreased nephropathy in men only, with no increased risk in women with T1D 166 The other 2 observational studies performed showed neither harm nor benefit in prevention of diabetic nephropathy 167;184 Physical Activity To Treat Diabetic Nephropathy A pre-post analysis 185 evaluated the effect of 3 weeks of physical activity and lowcalorie diet in treating existing nephropathy Table G3A13 in subjects with T2D Although albuminuria was reduced, the dietary intervention and/or associated weight loss may have confounded these results These data are somewhat promising but inconclusive Safety of Physical Activity With Existing Nephropathy The relevant literature
appears to show that exercise does not worsen resting proteinuria 186-188 In a cohort of 373 subjects with T1D, a strong correlation between overnight albumin excretion rate AER and post-exercise AER existed r 074, P 0001, and 52 of subjects had an elevated overnight AER preceding an elevated post-exercise AER 186 In a smaller cross-sectional study, Groop and colleagues 187 showed exercise did not increase protein excretion in 17 subjects newly diagnosed with T1D, but that 17 subjects with long-standing T1D had a significant increase in post-exercise excretion of albumin, 2-microglobulin, Kappa light chains, and IgG independent of whether resting AER was elevated n7 or normal n10 A small cohort study found no significant difference in time for nephropathy progression in 6 subjects with good unrestricted physical activity as compared with 7 subjects with self-restricted physical activity 188 Despite hypothetical adverse effects of increased proteinuria immediately after exercise 189, existing data show no progression of nephropathy with exercise and, in fact, increasing physical activity may decrease existing albuminuria, as described earlier in this section 185;190;191 In the
absence of primary data for other safety considerations in those with diabetic nephropathy, a review of these issues is outside the scope of this discussion, although guidelines exist 112;173
Diabetic Retinopathy
One moderate-sized prospective cohort study 192, and several cross-sectional 150;152;166;184;193 and retrospective 167;194 observational studies have evaluated the impact of physical activity on diabetic retinopathy Table G3A12 in T1D These limited data suggest that physical activity does not influence the risk of developing diabetic retinopathy The moderately sized cohort study 192 observed no difference in the incidence of retinopathy over 6 years in 606 T1D subjects with respect to current physical activity or historical participation in team sports, in contrast to an earlier cross-sectional analysis 193 in a subset of the same cohort population where a decreased prevalence of retinopathy in women who played team sports OR 046, P 005 or who reported current strenuous physical activity OR 034, P 005 was previously observed Two crosssectional analyses of slightly different subsets of a Finnish population with T1D found no
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association between physical activity and retinopathy 150;152 despite an association between physical activity and less nephropathy in those same studies 150;152 Of the 4 other cross-sectional studies performed, none showed any benefit or harm of physical activity in the prevention of diabetic retinopathy 166;167;184;194 Treatment of Diabetic Retinopathy A large cohort study reported no impact of self-reported current or historical physical activity measurements on retinopathy in a large cohort of T1D subjects with both nonproliferative and proliferative retinopathy at baseline measurement 192 Safety of Physical Activity With Existing Diabetic Retinopathy Although existing data raise concerns about the plausible causality of exercise-induced vitreous hemorrhages individuals with diabetic retinopathy, existing data have not conclusively shown a risk of moderate-intensity exercise in those with this condition 195 The 2 prospective studies evaluating the safety of exercise in humans with existing retinopathy have not shown an increased risk of retinopathy progression or of vitreous hemorrhage in this population The prospective cohort
study analysis by Cruickshanks and colleagues showed no risk of worsened retinopathy in those with T1D who were more physically active over a 6-year period as compared with their more sedentary counterparts, including a very small subset of self-described weight lifters 192 A pre-post exercise intervention study in 30 subjects with T1D or T2D and existing proliferative diabetic retinopathy 90 or greater or diabetic macular edema observed no newly documented vitreous hemorrhages attributable to a 12-week supervised exercise training program, although the study was under-powered to definitively determine vitreous hemorrhage risk 196 Given the preceding evidence, clinical providers have generally recommended moderateintensity exercise but advised against vigorous exercise regimens for those with proliferative retinopathy 112;173;183;197 and severe nonproliferative retinopathy 112 due to the theoretical yet unproven increased risk for vitreous hemorrhage and retinal detachments with vigorous exercise
Cardiovascular Safety of Physical Activity With Existing Microvascular Complications
Despite a lack of studies evaluating this practice, the most recent published standards of care
suggest that diabetic subjects with more than a 10 10-year risk for CV disease by the United Kingdom Prospective Diabetes Study risk calculator 198 should consider exercise stress testing to screen for latent ischemia before initiating vigorous aerobic exercise regimens that exceed the demands of everyday living 199
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Question 6: Do Physical Activity and Exercise Have a Role In Preventing Gestational Diabetes?
Conclusions Although no RCTs have been performed to demonstrate that physical activity can prevent gestational diabetes GDM, data from observational studies support that concept Available studies suggest that approximately 30 minutes per day of moderate-intensity physical activity is likely a sufficient dose to decrease the GDM risk 200 However, this suggestion is based on relatively few studies, and further studies should directly address the issue of dose-response Introduction Gestational diabetes is defined as diabetes first identified during pregnancy Overall, prevalence rates of GDM have increased from 19 in 1989-1990 to 42 in 2003-2004, a relative increase of 122 201 The
prevalence of GDM is 17 in obese women, and overweight women have a significantly greater risk of developing GDM than do nonoverweight women 202 It is estimated that up to 60 of women with GDM will develop T2D within 4 years of delivery 203 GDM can give rise to many adverse outcomes both to mother and infant It is associated with a greater likelihood of Caesarean section deliveries and other birth complications 204 Women with GDM also are more likely to have a difficult labor and delivery Babies of women with GDM are at increased risk of obesity and diabetes later in life as well as other comorbid conditions at birth 205 Given that women who develop GDM are at highly increased risk of developing T2D, understanding how to prevent and treat GDM is very important The role of physical activity in preventing and treating GDM has not been as well studied as for T2D Indeed, no RCTs have assessed whether GDM can be prevented by regular physical activity However, observational epidemiologic studies suggest overall that this may be the case Table G3A15, which summarizes these studies, can be accessed at http://wwwhealthgov/paguidelines/report/ Rationale
Data From Observational,
Epidemiological Studies
Several studies have shown that physical activity is associated with a significantly reduced risk of GDM 200 These studies reported that increased levels of physical activity assessed by questionnaire before pregnancy or during the first 20 weeks of pregnancy was associated with reductions in risk of GDM Overall the reduction in risk is about 50 when active women are compared to inactive women
Dose-Response Data
No RCTs have evaluated prospectively whether physical activity can prevent GDM or what doses might be effective for such a response Such trials would be of great value to establish
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the role of exercise and physical activity in GDM Available studies suggest that approximately 30 minutes per day of moderate intensity physical activity is likely a sufficient dose to decrease the GDM risk 200 However, this suggestion is based on relatively few studies, and further studies should directly address the issue of dose-response
Overall Summary and Conclusions
In summary, physical activity and exercise play a key role in preventing and treating metabolic
syndrome and T2D The evidence for T2D are the clearest because RCTs have been conducted to corroborate the findings of many observational trials, although, as mentioned previously, 2 of the 3 RCTs combined physical activity and diet in their lifestyle intervention The post-hoc findings on effects of physical activity in the absence of weight change, although consistent and strong, are therefore not considerd strong RCT data but rather are equivalent to the quality of prospective cohort study data The role of physical activity and exercise in treating T1D is still being established Current evidence suggests that benefits are likely, perhaps most of all in the area of reducing mortality, CVD risk factors, and microvascular complications For both T1D and T2D, physical activity may prevent the development of diabetic neuropathy and diabetic nephropathy Finally, it appears likely that physical activity and exercise may help prevent and treat gestational diabetes although more research is needed to establish these findings The amount of exercise that appears to be the most well accepted and documented across the conditions included in this section to date is 30 minutes of moderate
physical activity 5 days per week However, it is clear that benefits are obtained with even lower volumes of physical activity Walking is a beneficial form of physical activity and has been especially well documented as effective in T2D where it has been most extensively studied In the next section, the extensive research needs for further study in the area of Metabolic Health are documented
Research Needs
Although a considerable body of literature exists on the role of physical activity in promoting and maintaining metabolic health, a number of questions remain unanswered and require additional research: Available data indicate that regular physical activity is associated with reduced risk of metabolic syndrome However, it is not clear whether physical activity and exercise can be used in treating or reversing metabolic syndrome, and additional studies will help to clarify this issue Research is needed in diverse populations to determine whether the effects of physical activity across the range of metabolic health issues, including metabolic syndrome, T2D, T1D, and gestational diabetes, differ with race and ethnicity
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Further examination of the effects of physical activity on metabolic syndrome and T2D also is warranted to determine whether and how its effect differ in youth and adults Additional research evaluating dose-response patterns of exercise in preventing diabetes and cardiovascular outcomes in diabetes would make a valuable contribution to the metabolic health literature RCTs are needed to examine the effects of exercise on treating T1D in children and adults Good cardiovascular outcome data in response to physical activity in T1D is lacking and could potentially be obtained in adult-onset T1D Clinical studies in post-exercise hypoglycemia are needed to further study the intermittent high-intensity exercise approach to prevention and to compare extra carbohydrate versus lower insulin dosing approaches to treating T2D Research is needed on several issues related to gestational diabetes For example, RCTs are needed to determine whether physical activity can prevent gestational diabetes It also would be useful to have additional dose-response data on the role of exercise and physical activity in treating gestational diabetes
Reference
List
1 Ford ES, Giles WH, Dietz WH Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey JAMA 2002 Jan 16;2873:356-9 American Diabetes Association American Diabetes Association website 2008 Available from http://wwwdiabetesorg/homejsp National Institute of Diabetes and Digestive and Kidney Diseases, National Diabetes Information Clearinghouse US National Diabetes Information Clearinghouse 2005 Available from http://wwwniddknihgov/health/diabetes/ndichtm Vaidya D, Szklo M, Ding J, Tracy R, Liu K, Saad M, Ouyang P Agreement of two metabolic syndrome definitions and their association with subclinical atherosclerosis: multi-ethnic study of atherosclerosis cross sectional study Metab SyndrRelat Disord 2007 Dec;54:343-52 Executive Summary of The Third Report of The National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults Adult Treatment Panel III JAMA 2001 May 16;28519:2486-97
2 3
4
5
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6
Alberti KG, Zimmet PZ Definition, diagnosis and
classification of diabetes mellitus and its complications Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation DiabetMed 1998 Jul;157:539-53 Balkau B, Charles MA Comment on the provisional report from the WHO consultation European Group for the Study of Insulin Resistance EGIR DiabetMed 1999 May;165:442-3 Alberti KG, Zimmet P, Shaw J The metabolic syndrome–a new worldwide definition Lancet 2005 Sep 24;3669491:1059-62 Wareham NJ, Rennie KL The assessment of physical activity in individuals and populations: why try to be more precise about how physical activity is assessed? IntJObesRelat Metab Disord 1998 Aug;22 Suppl 2:S30-S38
7
8 9
10 Carroll S, Cooke CB, Butterly RJ Metabolic clustering, physical activity and fitness in nonsmoking, middle-aged men MedSciSports Exerc 2000 Dec;3212:2079-86 11 Irwin ML, Ainsworth BE, Mayer-Davis EJ, Addy CL, Pate RR, Durstine JL Physical activity and the metabolic syndrome in a tri-ethnic sample of women ObesRes 2002 Oct;1010:1030-7 12 Ekelund U, Griffin SJ, Wareham NJ Physical activity and metabolic risk in individuals with a family history of type 2 diabetes Diabetes Care 2007 Feb;302:337-42
13 Lakka TA, Laaksonen DE, Lakka HM, Mannikko N, Niskanen LK, Rauramaa R, Salonen JT Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome MedSciSports Exerc 2003 Aug;358:1279-86 14 Rennie KL, McCarthy N, Yazdgerdi S, Marmot M, Brunner E Association of the metabolic syndrome with both vigorous and moderate physical activity IntJEpidemiol 2003 Aug;324:600-6 15 Brage S, Wedderkopp N, Ekelund U, Franks PW, Wareham NJ, Andersen LB, Froberg K Features of the metabolic syndrome are associated with objectively measured physical activity and fitness in Danish children: the European Youth Heart Study EYHS Diabetes Care 2004 Sep;279:2141-8 16 Chuang SY, Chen CH, Chou P Prevalence of metabolic syndrome in a large health check-up population in Taiwan JChin MedAssoc 2004 Dec;6712:611-20 17 Franks PW, Ekelund U, Brage S, Wong MY, Wareham NJ Does the association of habitual physical activity with the metabolic syndrome differ by level of cardiorespiratory fitness? Diabetes Care 2004 May;275:1187-93
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18 Panagiotakos DB, Pitsavos C, Chrysohoou C, Skoumas J, Tousoulis D,
Toutouza M, Toutouzas P, Stefanadis C Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study AmHeart J 2004 Jan;1471:106-12 19 Rguibi M, Belahsen R Metabolic syndrome among Moroccan Sahraoui adult Women AmJHumBiol 2004 Sep;165:598-601 20 Villegas R, Creagh D, Hinchion R, OHalloran D, Perry IJ Prevalence and lifestyle determinants of the metabolic syndrome IrMedJ 2004 Nov;9710:300-3 21 Zhu S, St-Onge MP, Heshka S, Heymsfield SB Lifestyle behaviors associated with lower risk of having the metabolic syndrome Metabolism 2004 Nov;5311:1503-11 22 Adams RJ, Appleton S, Wilson DH, Taylor AW, Dal GE, Chittleborough C, Gill T, Ruffin R Population comparison of two clinical approaches to the metabolic syndrome: implications of the new International Diabetes Federation consensus definition Diabetes Care 2005 Nov;2811:2777-9 23 Bertrais S, Beyeme-Ondoua JP, Czernichow S, Galan P, Hercberg S, Oppert JM Sedentary behaviors, physical activity, and metabolic syndrome in middle-aged French subjects ObesRes 2005 May;135:936-44 24 Bo S, Gentile L, Ciccone G, Baldi C, Benini L, Dusio F, Lucia C, Forastiere G, Nuti C, Cassader M, et al The
metabolic syndrome and high C-reactive protein: prevalence and differences by sex in a southern-European population-based cohort Diabetes Metab ResRev 2005 Nov;216:515-24 25 Dunstan DW, Salmon J, Owen N, Armstrong T, Zimmet PZ, Welborn TA, Cameron AJ, Dwyer T, Jolley D, Shaw JE Associations of TV viewing and physical activity with the metabolic syndrome in Australian adults Diabetologia 2005 Nov;4811:2254-61 26 Ford ES, Kohl HW, III, Mokdad AH, Ajani UA Sedentary behavior, physical activity, and the metabolic syndrome among US adults ObesRes 2005 Mar;133:608-14 27 Lee WY, Jung CH, Park JS, Rhee EJ, Kim SW Effects of smoking, alcohol, exercise, education, and family history on the metabolic syndrome as defined by the ATP III Diabetes ResClinPract 2005 Jan;671:70-7 28 Misra KB, Endemann SW, Ayer M Leisure time physical activity and metabolic syndrome in Asian Indian immigrants residing in northern California EthnDis 2005;154:627-34
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29 Mohan V, Gokulakrishnan K, Deepa R, Shanthirani CS, Datta M Association of physical inactivity with components of metabolic syndrome and coronary
artery disease–the Chennai Urban Population Study CUPS no 15 DiabetMed 2005 Sep;229:1206-11 30 Nakanishi N, Takatorige T, Suzuki K Cigarette smoking and the risk of the metabolic syndrome in middle-aged Japanese male office workers IndHealth 2005 Apr;432:295-301 31 Onat A, Hergenc G, Keles I, Dogan Y, Turkmen S, Sansoy V Sex difference in development of diabetes and cardiovascular disease on the way from obesity and metabolic syndrome Metabolism 2005 Jun;546:800-8 32 Brien SE, Janssen I, Katzmarzyk PT Cardiorespiratory fitness and metabolic syndrome: US National Health and Nutrition Examination Survey 1999-2002 ApplPhysiol NutrMetab 2007 Feb;321:143-7 33 Desai MY, Dalal D, Santos RD, Carvalho JA, Nasir K, Blumenthal RS Association of body mass index, metabolic syndrome, and leukocyte count AmJCardiol 2006 Mar 15;976:835-8 34 Hassinen M, Komulainen P, Lakka TA, Vaisanen SB, Haapala I, Gylling H, Alen M, Schmidt-Trucksass A, Nissinen A, Rauramaa R Metabolic syndrome and the progression of carotid intima-media thickness in elderly women ArchInternMed 2006 Feb 27;1664:444-9 35 Liu J, Young TK, Zinman B, Harris SB, Connelly PW, Hanley AJ Lifestyle variables, non-traditional
cardiovascular risk factors, and the metabolic syndrome in an Aboriginal Canadian population ObesitySilverSpring 2006 Mar;143:500-8 36 Halldin M, Rosell M, de FU, Hellenius ML The metabolic syndrome: prevalence and association to leisure-time and work-related physical activity in 60-year-old men and women NutrMetab CardiovascDis 2007 Jun;175:349-57 37 Pitsavos C, Panagiotakos DB, Chrysohoou C, Kavouras S, Stefanadis C The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study EurJCardiovascPrevRehabil 2005 Apr;122:151-8 38 Brouwer BG, Visseren FL, van der GY The effect of leisure-time physical activity on the presence of metabolic syndrome in patients with manifest arterial disease The SMART study AmHeart J 2007 Dec;1546:1146-52 39 Ekelund U, Brage S, Franks PW, Hennings S, Emms S, Wareham NJ Physical activity energy expenditure predicts progression toward the metabolic syndrome
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independently of aerobic fitness in middle-aged healthy Caucasians: the Medical Research Council Ely Study Diabetes Care 2005
May;285:1195-200 40 Ekelund U, Franks PW, Sharp S, Brage S, Wareham NJ Increase in physical activity energy expenditure is associated with reduced metabolic risk independent of change in fatness and fitness Diabetes Care 2007 Aug;308:2101-6 41 Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa R, Lakka TA Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome Diabetes Care 2002 Sep;259:1612-8 42 Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K Risk factors for the metabolic syndrome: the Coronary Artery Risk Development in Young Adults CARDIA study, 1985-2001 Diabetes Care 2004 Nov;2711:2707-15 43 Palaniappan L, Carnethon MR, Wang Y, Hanley AJ, Fortmann SP, Haffner SM, Wagenknecht L Predictors of the incident metabolic syndrome in adults: the Insulin Resistance Atherosclerosis Study Diabetes Care 2004 Mar;273:788-93 44 Ferreira I, Twisk JW, van MW, Kemper HC, Stehouwer CD Development of fatness, fitness, and lifestyle from adolescence to the age of 36 years: determinants of the metabolic syndrome in young adults: the amsterdam growth and health longitudinal study ArchInternMed 2005 Jan
10;1651:42-8 45 Holme I, Tonstad S, Sogaard AJ, Larsen PG, Haheim LL Leisure time physical activity in middle age predicts the metabolic syndrome in old age: results of a 28-year follow-up of men in the Oslo study BMCPublic Health 2007;7147:154 46 Carnethon MR, Gidding SS, Nehgme R, Sidney S, Jacobs DR, Jr, Liu K Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors JAMA 2003 Dec 17;29023:3092-100 47 Ferreira I, Henry RM, Twisk JW, van MW, Kemper HC, Stehouwer CD The metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as independent determinants of arterial stiffness: the Amsterdam Growth and Health Longitudinal Study ArchInternMed 2005 Apr 25;1658:875-82 48 LaMonte MJ, Ainsworth BE, Durstine JL Influence of cardiorespiratory fitness on the association between C-reactive protein and metabolic syndrome prevalence in racially diverse women JWomens Health Larchmt 2005 Apr;143:233-9 49 Platat C, Wagner A, Klumpp T, Schweitzer B, Simon C Relationships of physical activity with metabolic syndrome features and low-grade inflammation in adolescents Diabetologia 2006 Sep;499:2078-85
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50 DuBose KD, Eisenmann JC, Donnelly JE Aerobic fitness attenuates the metabolic syndrome score in normal-weight, at-risk-for-overweight, and overweight children Pediatrics 2007 Nov;1205:e1262-e1268 51 Kelishadi R, Razaghi EM, Gouya MM, Ardalan G, Gheiratmand R, Delavari A, Motaghian M, Ziaee V, Siadat ZD, Majdzadeh R, et al Association of physical activity and the metabolic syndrome in children and adolescents: CASPIAN Study HormRes 2007;671:46-52 52 Eisenmann JC, Welk GJ, Ihmels M, Dollman J Fatness, fitness, and cardiovascular disease risk factors in children and adolescents MedSciSports Exerc 2007 Aug;398:1251-6 53 Eisenmann JC, Wickel EE, Welk GJ, Blair SN Relationship between adolescent fitness and fatness and cardiovascular disease risk factors in adulthood: the Aerobics Center Longitudinal Study ACLS AmHeart J 2005 Jan;1491:46-53 54 Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC, Rankinen T, Bouchard C Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study MedSciSports Exerc 2003 Oct;3510:1703-9 55 Johnson JL, Slentz CA, Houmard JA, Samsa GP, Duscha BD, Aiken
LB, McCartney JS, Tanner CJ, Kraus WE Exercise training amount and intensity effects on metabolic syndrome from Studies of a Targeted Risk Reduction Intervention through Defined Exercise AmJCardiol 2007 Dec 15;10012:1759-66 56 Jurca R, LaMonte MJ, Church TS, Earnest CP, Fitzgerald SJ, Barlow CE, Jordan AN, Kampert JB, Blair SN Associations of muscle strength and fitness with metabolic syndrome in men MedSciSports Exerc 2004 Aug;368:1301-7 57 Jurca R, LaMonte MJ, Barlow CE, Kampert JB, Church TS, Blair SN Association of muscular strength with incidence of metabolic syndrome in men MedSciSports Exerc 2005 Nov;3711:1849-55 58 Wijndaele K, Duvigneaud N, Matton L, Duquet W, Thomis M, Beunen G, Lefevre J, Philippaerts RM Muscular strength, aerobic fitness, and metabolic syndrome risk in Flemish adults MedSciSports Exerc 2007 Feb;392:233-40 59 Blair SN, Kampert JB, Kohl HW, III, Barlow CE, Macera CA, Paffenbarger RS, Jr, Gibbons LW Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women JAMA 1996 Jul 17;2763:205-10
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60 Wei M, Gibbons LW, Kampert JB, Nichaman MZ, Blair SN Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes AnnInternMed 2000 Apr 18;1328:605-11 61 Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS, Jr Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus NEnglJMed 1991 Jul 18;3253:147-52 62 Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE Physical activity and incidence of non-insulindependent diabetes mellitus in women Lancet 1991 Sep 28;3388770:774-8 63 Hu FB, Sigal RJ, Rich-Edwards JW, Colditz GA, Solomon CG, Willett WC, Speizer FE, Manson JE Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study JAMA 1999 Oct 20;28215:1433-9 64 Wannamethee SG, Shaper AG, Alberti KG Physical activity, metabolic factors, and the incidence of coronary heart disease and type 2 diabetes ArchInternMed 2000 Jul 24;16014:2108-16 65 Okada K, Hayashi T, Tsumura K, Suematsu C, Endo G, Fujii S Leisure-time physical activity at weekends and the risk of Type 2 diabetes mellitus in Japanese men: the
Osaka Health Survey DiabetMed 2000 Jan;171:53-8 66 Folsom AR, Kushi LH, Hong CP Physical activity and incident diabetes mellitus in postmenopausal women AmJPublic Health 2000 Jan;901:134-8 67 Hu FB, Stampfer MJ, Solomon C, Liu S, Colditz GA, Speizer FE, Willett WC, Manson JE Physical activity and risk for cardiovascular events in diabetic women AnnInternMed 2001 Jan 16;1342:96-105 68 Hu G, Qiao Q, Silventoinen K, Eriksson JG, Jousilahti P, Lindstrom J, Valle TT, Nissinen A, Tuomilehto J Occupational, commuting, and leisure-time physical activity in relation to risk for Type 2 diabetes in middle-aged Finnish men and women Diabetologia 2003 Mar;463:322-9 69 Weinstein AR, Sesso HD, Lee IM, Cook NR, Manson JE, Buring JE, Gaziano JM Relationship of physical activity vs body mass index with type 2 diabetes in women JAMA 2004 Sep 8;29210:1188-94 70 Hsia J, Wu L, Allen C, Oberman A, Lawson WE, Torrens J, Safford M, Limacher MC, Howard BV Physical activity and diabetes risk in postmenopausal women AmJPrevMed 2005 Jan;281:19-25
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71 Lynch J, Helmrich SP, Lakka TA, Kaplan GA, Cohen RD,
Salonen R, Salonen JT Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men ArchInternMed 1996 Jun 24;15612:1307-14 72 Wei M, Gibbons LW, Mitchell TL, Kampert JB, Lee CD, Blair SN The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men AnnInternMed 1999 Jan 19;1302:89-96 73 Sui X, Hooker SP, Lee IM, Church TS, Colabianchi N, Lee CD, Blair SN A prospective study of cardiorespiratory fitness and risk of type 2 diabetes in women Diabetes Care 2008 Mar;313:550-5 74 Bassuk SS, Manson JE Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease JApplPhysiol 2005 Sep;993:1193-204 75 Jeon CY, Lokken RP, Hu FB, van Dam RM Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review Diabetes Care 2007 Mar;303:74452 76 Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, et al Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance The Da Qing IGT and Diabetes Study Diabetes
Care 1997 Apr;204:537-44 77 Eriksson J, Lindstrom J, Valle T, Aunola S, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Lauhkonen M, Lehto P, et al Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study DPS in Finland Study design and 1-year interim report on the feasibility of the lifestyle intervention programme Diabetologia 1999 Jul;427:793-801 78 Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, et al Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance NEnglJMed 2001 May 3;34418:1343-50 79 Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin NEnglJMed 2002 Feb 7;3466:393-403 80 Hamman RF, Wing RR, Edelstein SL, Lachin JM, Bray GA, Delahanty L, Hoskin M, Kriska AM, Mayer-Davis EJ, Pi-Sunyer X, et al Effect of weight loss with lifestyle intervention on risk of diabetes Diabetes Care 2006 Sep;299:2102-7
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81 Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, Aunola S, Keinanen-Kiukaanniemi S, Laakso M, Valle TT, et al Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study Diabetes 2005 Jan;541:158-65 82 Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, Hamalainen H, Harkonen P, Keinanen-Kiukaanniemi S, Laakso M, et al Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study Lancet 2006 Nov 11;3689548:1673-9 83 Schneider SH, Amorosa LF, Khachadurian AK, Ruderman NB Studies on the mechanism of improved glucose control during regular exercise in type 2 noninsulin-dependent diabetes Diabetologia 1984 May;265:355-60 84 Regensteiner JG, Bauer TA, Reusch JE, Brandenburg SL, Sippel JM, Vogelsong AM, Smith S, Wolfel EE, Eckel RH, Hiatt WR Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus JApplPhysiol 1998 Jul;851:310-7 85 Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG Diastolic dysfunction in normotensive men with
well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy Diabetes Care 2001 Jan;241:5-10 86 Regensteiner JG, Groves BM, Bauer TA, Reusch JEB, Smith SC, Wolfel EE Recently diagnosed type 2 diabetes mellitus adversely affects cardiac function during exercise Diabetes 2002;51Suppl 2:A59 87 Bauer TA, Reusch JE, Levi M, Regensteiner JG Skeletal muscle deoxygenation after the onset of moderate exercise suggests slowed microvascular blood flow kinetics in type 2 diabetes Diabetes Care 2007 Nov;3011:2880-5 88 Devlin JT, Hirshman M, Horton ED, Horton ES Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise Diabetes 1987 Apr;364:434-9 89 Thomas DE, Elliott EJ, Naughton GA Exercise for type 2 diabetes mellitus CochraneDatabaseSystRev 2006;3:CD002968 90 Brandenburg SL, Reusch JE, Bauer TA, Jeffers BW, Hiatt WR, Regensteiner JG Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes Diabetes Care 1999 Oct;2210:1640-6 91 Wilmore JH, Green JS, Stanforth PR, Gagnon J, Rankinen T, Leon AS, Rao DC, Skinner JS, Bouchard C Relationship of
changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent
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diabetes mellitus risk factors with endurance training: the HERITAGE Family Study Metabolism 2001 Nov;5011:1255-63 92 Gaillard TR, Sherman WM, Devor ST, Kirby TE, Osei K Importance of aerobic fitness in cardiovascular risks in sedentary overweight and obese African-American women NursRes 2007 Nov;566:407-15 93 National Institute of Diabetes and Digestive and Kidney Disease NIDDK, NIH Diabetes Prevention Program 2002 Available from http://diabetesniddknihgov/dm/pubs/preventionprogram/ 94 Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial AnnInternMed 2005 Apr 19;1428:611-9 95 Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose
tolerance IDPP-1 Diabetologia 2006 Feb;492:289-97 96 Kosaka K, Noda M, Kuzuya T Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males Diabetes ResClinPract 2005 Feb;672:152-62 97 Rodriguez BL, Fujimoto WY, Mayer-Davis EJ, Imperatore G, Williams DE, Bell RA, Wadwa RP, Palla SL, Liu LL, Kershnar A, et al Prevalence of cardiovascular disease risk factors in US children and adolescents with diabetes: the SEARCH for diabetes in youth study Diabetes Care 2006 Aug;298:1891-6 98 Gungor N, Thompson T, Sutton-Tyrrell K, Janosky J, Arslanian S Early signs of cardiovascular disease in youth with obesity and type 2 diabetes Diabetes Care 2005 May;285:1219-21 99 Ribeiro MM, Silva AG, Santos NS, Guazzelle I, Matos LN, Trombetta IC, Halpern A, Negrao CE, Villares SM Diet and exercise training restore blood pressure and vasodilatory responses during physiological maneuvers in obese children Circulation 2005 Apr 19;11115:1915-23 100 Nassis GP, Papantakou K, Skenderi K, Triandafillopoulou M, Kavouras SA, Yannakoulia M, Chrousos GP, Sidossis LS Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and
inflammatory markers in overweight and obese girls Metabolism 2005 Nov;5411:1472-9
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101 Carrel AL, Clark RR, Peterson SE, Nemeth BA, Sullivan J, Allen DB Improvement of fitness, body composition, and insulin sensitivity in overweight children in a school-based exercise program: a randomized, controlled study ArchPediatrAdolescMed 2005 Oct;15910:963-8 102 Nwobu CO, Johnson CC Targeting obesity to reduce the risk for type 2 diabetes and other co-morbidities in African American youth: a review of the literature and recommendations for prevention DiabVascDisRes 2007 Dec;44:311-9 103 Sallis JF, McKenzie TL, Alcaraz JE, Kolody B, Faucette N, Hovell MF The effects of a 2-year physical education program SPARK on physical activity and fitness in elementary school students Sports, Play and Active Recreation for Kids AmJPublic Health 1997 Aug;878:1328-34 104 Pangrazi RP, Beighle A, Vehige T, Vack C Impact of Promoting Lifestyle Activity for Youth PLAY on childrens physical activity JSch Health 2003 Oct;738:31721 105 McGavock J, Sellers E, Dean H Physical activity for the prevention and
management of youth-onset type 2 diabetes mellitus: focus on cardiovascular complications DiabVascDisRes 2007 Dec;44:305-10 106 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 ArchPediatrAdolescMed 2001 Mar;1553:360-5 107 Berkey CS, Rockett HR, Gillman MW, Colditz GA One-year changes in activity and in inactivity among 10- to 15-year-old boys and girls: relationship to change in body mass index Pediatrics 2003 Apr;1114 Pt 1:836-43 108 Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes PediatrDiabetes 2007 Apr;82:74-87 109 Castaneda C, Layne JE, Munoz-Orians L, Gordon PL, Walsmith J, Foldvari M, Roubenoff R, Tucker KL, Nelson ME A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes Diabetes Care 2002
Dec;2512:2335-41 110 Dunstan DW, Daly RM, Owen N, Jolley D, De Court, Shaw J, Zimmet P Highintensity resistance training improves glycemic control in older patients with type 2 diabetes Diabetes Care 2002 Oct;2510:1729-36
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111 Sigal RJ, Kenny GP, Boule NG, Wells GA, Prudhomme D, Fortier M, Reid RD, Tulloch H, Coyle D, Phillips P, et al Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial AnnInternMed 2007 Sep 18;1476:357-69 112 Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White RD Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association Diabetes Care 2006 Jun;296:1433-8 113 Flood L, Constance A Diabetes and exercise safety AmJNurs 2002 Jun;1026:4755 114 Blair SN, Kohl HW, III, Paffenbarger RS, Jr, Clark DG, Cooper KH, Gibbons LW Physical fitness and all-cause mortality A prospective study of healthy men and women JAMA 1989 Nov 3;26217:2395-401 115 Gregg EW, Gerzoff RB, Caspersen CJ, Williamson DF, Narayan KM Relationship of walking to mortality among US
adults with diabetes ArchInternMed 2003 Jun 23;16312:1440-7 116 Tanasescu M, Leitzmann MF, Rimm EB, Hu FB Physical activity in relation to cardiovascular disease and total mortality among men with type 2 diabetes Circulation 2003 May 20;10719:2435-9 117 Hu G, Eriksson J, Barengo NC, Lakka TA, Valle TT, Nissinen A, Jousilahti P, Tuomilehto J Occupational, commuting, and leisure-time physical activity in relation to total and cardiovascular mortality among Finnish subjects with type 2 diabetes Circulation 2004 Aug 10;1106:666-73 118 Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes Diabetes Care 2005 Apr;284:799-805 119 Snowling NJ, Hopkins WG Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients: a meta-analysis Diabetes Care 2006 Nov;2911:2518-27 120 Kelley GA, Kelley KS Effects of aerobic exercise on lipids and lipoproteins in adults with type 2 diabetes: a meta-analysis of randomized-controlled trials Public Health 2007 Sep;1219:643-55 121 Zoppini G, Targher G, Zamboni C, Venturi C,
Cacciatori V, Moghetti P, Muggeo M Effects of moderate-intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes NutrMetab CardiovascDis 2006 Dec;168:543-9
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122 Kelley DE Action for health in diabetes: the look AHEAD clinical trial CurrDiabRep 2002 Jun;23:207-9 123 Ryan DH, Espeland MA, Foster GD, Haffner SM, Hubbard VS, Johnson KC, Kahn SE, Knowler WC, Yanovski SZ Look AHEAD Action for Health in Diabetes: design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes Control ClinTrials 2003 Oct;245:610-28 124 Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, Williamson D, Berkowitz RI, Kelley DE, Tomchee C, Hill JO, et al The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it ObesitySilverSpring 2006 May;145:737-52 125 Shinji S, Shigeru M, Ryusei U, Mitsuru M, Shigehiro K Adherence to a home-based exercise program and incidence of cardiovascular disease in type 2 diabetes patients IntJSports Med 2007
Oct;2810:877-9 126 Church TS, LaMonte MJ, Barlow CE, Blair SN Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes ArchInternMed 2005 Oct 10;16518:2114-20 127 Seyoum B, Estacio RO, Berhanu P, Schrier RW Exercise capacity is a predictor of cardiovascular events in patients with type 2 diabetes mellitus DiabVascDisRes 2006 Dec;33:197-201 128 McAuley PA, Myers JN, Abella JP, Tan SY, Froelicher VF Exercise capacity and body mass as predictors of mortality among male veterans with type 2 diabetes Diabetes Care 2007 Jun;306:1539-43 129 Trichopoulou A, Psaltopoulou T, Orfanos P, Trichopoulos D Diet and physical activity in relation to overall mortality amongst adult diabetics in a general population cohort JInternMed 2006 Jun;2596:583-91 130 Smith TC, Wingard DL, Smith B, Kritz-Silverstein D, Barrett-Connor E Walking decreased risk of cardiovascular disease mortality in older adults with diabetes JClinEpidemiol 2007 Mar;603:309-17 131 Batty GD, Shipley MJ, Marmot M, Smith GD Physical activity and cause-specific mortality in men with Type 2 diabetes/impaired glucose tolerance: evidence from the Whitehall study
DiabetMed 2002 Jul;197:580-8 132 Gill JM, Malkova D Physical activity, fitness and cardiovascular disease risk in adults: interactions with insulin resistance and obesity ClinSciLond 2006 Apr;1104:409-25
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133 Boule NG, Kenny GP, Haddad E, Wells GA, Sigal RJ Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in Type 2 diabetes mellitus Diabetologia 2003 Aug;468:1071-81 134 Liese AD, DAgostino RB, Jr, Hamman RF, Kilgo PD, Lawrence JM, Liu LL, Loots B, Linder B, Marcovina S, Rodriguez B, et al The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study Pediatrics 2006 Oct;1184:1510-8 135 Moy CS, Songer TJ, LaPorte RE, Dorman JS, Kriska AM, Orchard TJ, Becker DJ, Drash AL Insulin-dependent diabetes mellitus, physical activity, and death AmJEpidemiol 1993 Jan 1;1371:74-81 136 Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 2000 Apr;494:626-32 137 Schauer IE, Bergman SJ, Maahs DM, Kretowski A, Eckel RH, Rewers
M Insulin sensitivity and free fatty acid supression differ in persons with type 1 diabetes compared to non-diabetic controls: the cacti study Diabetes 2008;In Press 138 Wallberg-Henriksson H, Gunnarsson R, Henriksson J, DeFronzo R, Felig P, Ostman J, Wahren J Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training Diabetes 1982 Dec;3112:1044-50 139 Zinman B, Zuniga-Guajardo S, Kelly D Comparison of the acute and long-term effects of exercise on glucose control in type I diabetes Diabetes Care 1984 Nov;76:515-9 140 Wallberg-Henriksson H, Gunnarsson R, Rossner S, Wahren J Long-term physical training in female type 1 insulin-dependent diabetic patients: absence of significant effect on glycaemic control and lipoprotein levels Diabetologia 1986 Jan;291:53-7 141 Huttunen NP, Lankela SL, Knip M, Lautala P, Kaar ML, Laasonen K, Puukka R Effect of once-a-week training program on physical fitness and metabolic control in children with IDDM Diabetes Care 1989 Nov;1210:737-40 142 Roberts L, Jones TW, Fournier PA Exercise training and glycemic control in adolescents with poorly controlled
type 1 diabetes mellitus JPediatrEndocrinolMetab 2002 May;155:621-7 143 Ramalho AC, de Lourdes LM, Nunes F, Cambui Z, Barbosa C, Andrade A, Viana A, Martins M, Abrantes V, Aragao C, et al The effect of resistance versus aerobic training on metabolic control in patients with type-1 diabetes mellitus Diabetes ResClinPract 2006 Jun;723:271-6
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144 Harmer AR, Chisholm DJ, McKenna MJ, Morris NR, Thom JM, Bennett G, Flack JR High-intensity training improves plasma glucose and acid-base regulation during intermittent maximal exercise in type 1 diabetes Diabetes Care 2007 May;305:1269-71 145 Peterson CM, Jones RL, Esterly JA, Wantz GE, Jackson RL Changes in basement membrane thickening and pulse volume concomitant with improved glucose control and exercise in patients with insulin-dependent diabetes mellitus Diabetes Care 1980 Sep;35:586-9 146 Campaigne BN, Gilliam TB, Spencer ML, Lampman RM, Schork MA Effects of a physical activity program on metabolic control and cardiovascular fitness in children with insulin-dependent diabetes mellitus Diabetes Care 1984 Jan;71:57-62 147 Bak JF,
Jacobsen UK, Jorgensen FS, Pedersen O Insulin receptor function and glycogen synthase activity in skeletal muscle biopsies from patients with insulindependent diabetes mellitus: effects of physical training JClinEndocrinolMetab 1989 Jul;691:158-64 148 Durak EP, Jovanovic-Peterson L, Peterson CM Randomized crossover study of effect of resistance training on glycemic control, muscular strength, and cholesterol in type I diabetic men Diabetes Care 1990 Oct;1310:1039-43 149 Ligtenberg PC, Blans M, Hoekstra JB, van dT, I, Erkelens DW No effect of longterm physical activity on the glycemic control in type 1 diabetes patients: a crosssectional study NethJMed 1999 Aug;552:59-63 150 Waden J, Tikkanen H, Forsblom C, Fagerudd J, Pettersson-Fernholm K, Lakka T, Riska M, Groop PH Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: the FinnDiane study Diabetes Care 2005 Apr;284:777-82 151 Herbst A, Kordonouri O, Schwab KO, Schmidt F, Holl RW Impact of physical activity on cardiovascular risk factors in children with type 1 diabetes: a multicenter study of 23,251 patients Diabetes Care 2007 Aug;308:2098-100 152 Waden J, Thorn LM, Forsblom C,
Lakka T, Saraheimo M, Rosengard-Barlund M, Heikkila O, Wessman M, Turunen JA, Parkkonen M, et al Leisure-time physical activity is associated with the metabolic syndrome in type 1 diabetes: effect of the PPARgamma Pro12Ala polymorphism: the FinnDiane Study Diabetes Care 2007 Jun;306:1618-20 153 Lehmann R, Kaplan V, Bingisser R, Bloch KE, Spinas GA Impact of physical activity on cardiovascular risk factors in IDDM Diabetes Care 1997 Oct;2010:1603-11
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154 Zinman B, Ruderman N, Campaigne BN, Devlin JT, Schneider SH Physical activity/exercise and diabetes Diabetes Care 2004 Jan;27 Suppl 1:S58-S62 155 Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, et al Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin Diabetes Care 2006 Oct;2910:2200-4 156 Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson JL Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus
insulin regimen ultralentelispro Diabetes Care 2001 Apr;244:625-30 157 Grimm JJ, Ybarra J, Berne C, Muchnick S, Golay A A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients Diabetes Metab 2004 Nov;305:465-70 158 Guelfi KJ, Jones TW, Fournier PA The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes Diabetes Care 2005 Jun;286:1289-94 159 Bussau VA, Ferreira LD, Jones TW, Fournier PA The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes Diabetes Care 2006 Mar;293:601-6 160 Bussau VA, Ferreira LD, Jones TW, Fournier PA A 10-s sprint performed prior to moderate-intensity exercise prevents early post-exercise fall in glycaemia in individuals with type 1 diabetes Diabetologia 2007 Sep;509:1815-8 161 Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes AmJPhysiol EndocrinolMetab 2007 Mar;2923:E865-E870 162 Guelfi KJ, Jones TW,
Fournier PA New insights into managing the risk of hypoglycaemia associated with intermittent high-intensity exercise in individuals with type 1 diabetes mellitus: implications for existing guidelines Sports Med 2007;3711:937-46 163 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus The Diabetes Control and Complications Trial Research Group NEnglJMed 1993 Sep 30;32914:97786
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164 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS 33 UK Prospective Diabetes Study UKPDS Group Lancet 1998 Sep 12;3529131:837-53 165 Balducci S, Iacobellis G, Parisi L, Di BN, Calandriello E, Leonetti F, Fallucca F Exercise training can modify the natural history of diabetic peripheral neuropathy JDiabetes Complications 2006 Jul;204:216-23 166 Kriska AM, LaPorte RE, Patrick SL, Kuller LH, Orchard TJ The association of physical activity and diabetic complications in individuals with
insulin-dependent diabetes mellitus: the Epidemiology of Diabetes Complications Study–VII JClinEpidemiol 1991;4411:1207-14 167 Orchard TJ, Dorman JS, Maser RE, Becker DJ, Ellis D, LaPorte RE, Kuller LH, Wolfson SK, Jr, Drash AL Factors associated with avoidance of severe complications after 25 yr of IDDM Pittsburgh Epidemiology of Diabetes Complications Study I Diabetes Care 1990 Jul;137:741-7 168 Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, Hamwi J, Pollari D, Bixby B, Howard J, et al Lifestyle intervention for pre-diabetic neuropathy Diabetes Care 2006 Jun;296:1294-9 169 Colberg SR, Parson HK, Nunnold T, Holton DR, Swain DP, Vinik AI Change in cutaneous perfusion following 10 weeks of aerobic training in Type 2 diabetes JDiabetes Complications 2005 Sep;195:276-83 170 Colberg SR, Parson HK, Nunnold T, Herriott MT, Vinik AI Effect of an 8-week resistance training program on cutaneous perfusion in type 2 diabetes MicrovascRes 2006 Mar;712:121-7 171 Colberg SR, Stansberry KB, McNitt PM, Vinik AI Chronic exercise is associated with enhanced cutaneous blood flow in type 2 diabetes JDiabetes Complications 2002 Mar;162:139-45 172 Colberg SR, Parson HK, Holton
DR, Nunnold T, Vinik AI Cutaneous blood flow in type 2 diabetic individuals after an acute bout of maximal exercise Diabetes Care 2003 Jun;266:1883-8 173 Graham C, Lasko-McCarthey P Exercise options for persons with diabetic complications Diabetes Educ 1990 May;163:212-20 174 Armstrong DG, Lavery LA, Holtz-Neiderer K, Mohler MJ, Wendel CS, Nixon BP, Boulton AJ Variability in activity may precede diabetic foot ulceration Diabetes Care 2004 Aug;278:1980-4
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175 Lemaster JW, Reiber GE, Smith DG, Heagerty PJ, Wallace C Daily weight-bearing activity does not increase the risk of diabetic foot ulcers MedSciSports Exerc 2003 Jul;357:1093-9 176 Giacomozzi C, Caselli A, Macellari V, Giurato L, Lardieri L, Uccioli L Walking strategy in diabetic patients with peripheral neuropathy Diabetes Care 2002 Aug;258:1451-7 177 Kanade RV, van Deursen RW, Harding K, Price P Walking performance in people with diabetic neuropathy: benefits and threats Diabetologia 2006 Aug;498:1747-54 178 Dingwell JB, Cusumano JP, Sternad D, Cavanagh PR Slower speeds in patients with diabetic neuropathy lead to improved
local dynamic stability of continuous overground walking JBiomech 2000 Oct;3310:1269-77 179 Dingwell JB, Cavanagh PR Increased variability of continuous overground walking in neuropathic patients is only indirectly related to sensory loss GaitPosture 2001 Jul;141:1-10 180 Dingwell JB, Kang HG, Marin LC The effects of sensory loss and walking speed on the orbital dynamic stability of human walking JBiomech 2007;408:1723-30 181 Mueller MJ, Minor SD, Schaaf JA, Strube MJ, Sahrmann SA Relationship of plantar-flexor peak torque and dorsiflexion range of motion to kinetic variables during walking PhysTher 1995 Aug;758:684-93 182 Novak P, Burger H, Marincek C, Meh D Influence of foot pain on walking ability of diabetic patients JRehabilMed 2004 Nov;366:249-52 183 Wallberg-Henriksson H, Rincon J, Zierath JR Exercise in the management of noninsulin-dependent diabetes mellitus Sports Med 1998 Jan;251:25-35 184 Samanta A, Burden AC, Jagger C A comparison of the clinical features and vascular complications of diabetes between migrant Asians and Caucasians in Leicester, UK Diabetes ResClinPract 1991 Dec;143:205-13 185 Hotta O, Taguma Y, Mitsuoka M, Takeshita K, Takahashi H Urinary
albumin excretion in patients with non-insulin-dependent diabetes mellitus in an early microalbuminuric stage Nephron 1991;581:23-6 186 Garg SK, Chase HP, Shapiro H, Harris S, Osberg IM Exercise versus overnight albumin excretion rates in subjects with type 1 diabetes Diabetes ResClinPract 1995 Apr;281:51-5
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187 Groop L, Stenman S, Groop PH, Makipernaa A, Teppo AM The effect of exercise on urinary excretion of different size proteins in patients with insulin-dependent diabetes mellitus ScandJClinLab Invest 1990 Sep;505:525-32 188 Matsuoka K, Nakao T, Atsumi Y, Takekoshi H Exercise regimen for patients with diabetic nephropathy JDiabetComplications 1991 Apr;52-3:98-100 189 Morgensen CE Nephropathy: early In: Ruderman N, Devlin JT, Schneider SH, et al, editors Handbook of Exercise in Diabetes Alexandria, VA: American Diabetes Association; 2002 p 433-49 190 Fredrickson SK, Ferro TJ, Schutrumpf AC Disappearance of microalbuminuria in a patient with type 2 diabetes and the metabolic syndrome in the setting of an intense exercise and dietary program with sustained weight reduction
Diabetes Care 2004 Jul;277:1754-5 191 Lazarevic G, Antic S, Vlahovic P, Djordjevic V, Zvezdanovic L, Stefanovic V Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients Ren Fail 2007;292:199-205 192 Cruickshanks KJ, Moss SE, Klein R, Klein BE Physical activity and the risk of progression of retinopathy or the development of proliferative retinopathy Ophthalmology 1995 Aug;1028:1177-82 193 Cruickshanks KJ, Moss SE, Klein R, Klein BE Physical activity and proliferative retinopathy in people diagnosed with diabetes before age 30 yr Diabetes Care 1992 Oct;1510:1267-72 194 LaPorte RE, Dorman JS, Tajima N, Cruickshanks KJ, Orchard TJ, Cavender DE, Becker DJ, Drash AL Pittsburgh Insulin-Dependent Diabetes Mellitus Morbidity and Mortality Study: physical activity and diabetic complications Pediatrics 1986 Dec;786:1027-33 195 Anderson B, Jr Activity and diabetic vitreous hemorrhages Ophthalmology 1980 Mar;873:173-5 196 Bernbaum M, Albert SG, Cohen JD, Drimmer A Cardiovascular conditioning in individuals with diabetic retinopathy Diabetes Care 1989 Nov;1210:740-2 197 Albert SG, Bernbaum M Exercise for patients with diabetic retinopathy Diabetes Care
1995 Jan;181:130-2 198 Stevens RJ, Kothari V, Adler AI, Stratton IM The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes UKPDS 56 ClinSciLond 2001 Dec;1016:671-9
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199 Summary of revisions for the 2006 Clinical Practice Recommendations Diabetes Care 2006 Jan;29 Suppl 1:S3 200 Dempsey JC, Butler CL, Williams MA No need for a pregnant pause: physical activity may reduce the occurrence of gestational diabetes mellitus and preeclampsia ExercSport SciRev 2005 Jul;333:141-9 201 Getahun D, Nath C, Ananth CV, Chavez MR, Smulian JC Gestational diabetes in the United States: temporal trends 1989 through 2004 AmJObstetGynecol 2008 Feb 15 202 Linne Y Effects of obesity on womens reproduction and complications during pregnancy ObesRev 2004 Aug;53:137-43 203 Kelly C, Booth GL Diabetes in Canadian Women BMCWomens Health 2004 Aug 25;4 Suppl 1:S16 204 Jovanovic L What is so bad about a big baby? Diabetes Care 2001 Aug;248:13178 205 Schaefer-Graf UM, Kleinwechter H Diagnosis and new approaches in the therapy of gestational diabetes mellitus CurrDiabetes Rev
2006 Aug;23:343-52
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Source:health.gov
