***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: INTRODUCTION AND PURPOSE Physical inactivity in postmenopausal women contributes to a rise in atherogenic risk factors associated with the metabolic syndrome . Although regular physical activity positively contributes to health , inactivity progressively increases with age . The Dose Response to Exercise in Women aged 45 - 75 yr ( DREW ) study is design ed to investigate the effect of different amounts of exercise training on cardiorespiratory fitness and risk factors for cardiovascular disease ( CVD ) in postmenopausal women at moderately increased risk of CVD . METHODS DREW will recruit 450 sedentary , healthy , postmenopausal women with a body mass index of 25 - 40 kg.m-2 , resting systolic blood pressure ( BP ) of 120 - 159 mm Hg , and a resting diastolic BP of < or = 99 mm Hg . Laboratory and self-report measures completed at baseline and 6 months include maximal oxygen consumption ( .VO2max ) , resting BP , anthropometry , dietary habits , physical activity history , medication use , menstrual history , personal and family medical history , and fasting HDL cholesterol , LDL cholesterol , triglycerides , and glucose . Eligible participants are r and omly assigned to a nonexercise group or one of three exercise groups . Participants exercise 3 to 4x wk-1 at a heart rate equivalent to 50 % of .VO2max expending 4 , 8 , or 12 kcal.kg-1.wk-1 , depending on group assignment . This study will allow quantification of possible dose-response relations ( 50 % , 100 % , and 150 % of the consensus physical activity recommendation ) between exercise training and study outcomes . CONCLUSION DREW can make important contributions to our underst and ing of the effects of physical activity in postmenopausal women and help refine public health and clinical recommendations for this group CONTEXT Although many studies suggest that physical activity may reduce risk of type 2 diabetes , the role of moderate-intensity activity such as walking is not well understood . OBJECTIVES To examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes . DESIGN AND SETTING The Nurses ' Health Study , a prospect i ve cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986 , with up date s in 1988 and 1992 . PARTICIPANTS A total of 70,102 female nurses aged 40 to 65 years who did not have diabetes , cardiovascular disease , or cancer at baseline ( 1986 ) . MAIN OUTCOME MEASURE Risk of type 2 diabetes by quintile of metabolic equivalent task ( MET ) score , based on time spent per week on each of 8 common physical activities , including  walking .  RESULTS During 8 years of follow-up ( 534 , 928 person-years ) , we documented 1419 incident cases of type 2 diabetes . After adjusting for age , smoking , alcohol use , history of hypertension , history of high cholesterol level , and other covariates , the relative risks ( RRs ) of developing type 2 diabetes across quintiles of physical activity ( least to most ) were 1.0 , 0.77 , 0.75 , 0.62 , and 0.54 ( P for trend < .001 ) ; after adjusting for body mass index ( BMI ) , RRs were 1.0 , 0.84 , 0.87 , 0.77 , and 0.74 ( P for trend = .002 ) . Among women who did not perform vigorous activity , multivariate RRs of type 2 diabetes across quintiles of MET score for walking were 1.0 , 0.91,0.73 , 0.69 , and 0.58 ( P for trend < .001 ) . After adjusting for BMI , the trend remained statistically significant ( RRs were 1.0 , 0.95 , 0.80 , 0.81 , 0.74 ; P for trend = .01 ) . Faster usual walking pace was independently associated with decreased risk . Equivalent energy expenditures from walking and vigorous activity result ed in comparable magnitudes of risk reduction . CONCLUSIONS Our data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes , including physical activity of moderate intensity and duration CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P < .05 ) compared with the control group . All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P < .05 ) and combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P < .05 ) compared with the control group . CONCLUSIONS Among patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133 PURPOSE The Studies of a Targeted Risk Reduction Intervention through Defined Exercise ( STRRIDE ) trial is a r and omized controlled clinical trial design ed to study the effects of exercise training regimens differing in dose ( kcal.wk-1 ) and /or intensity ( relative to peak VO2 ) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans . METHODS We will recruit 384 subjects and r and omly assign them to one of three exercise training regimens or to a sedentary control group . The recruiting goal is to attain a subject population that is 50 % female and 30 % ethnic minority . The overall strategy is to use grade d exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle ( fiber type , metabolic capacity , and /or capillary surface area ) account for improvements in insulin action and parameters of lipoprotein metabolism . We will study these variables before and after exercise training , and over the course of a 2-wk detraining period . The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density . RESULTS The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle . CONCLUSION Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better underst and ing of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group .  The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity .  The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system PURPOSE The INFLAME study is design ed to determine the effect of exercise training on elevated high-sensitivity C-Reactive Protein ( CRP ) concentrations in initially sedentary women and men . METHODS INFLAME will recruit 170 healthy , sedentary women and men with elevated CRP ( > or=2.0 mg/L ) to be r and omized to either an exercise group or non-exercise control group .  Exercising individuals will participate in four months of supervised aerobic exercise with a total energy expenditure of 16 kcal kg(-1 ) week(-1 ) ( KKW ) . Exercise intensity will be 60 - 80 % of maximal oxygen consumption ( VO(2 ) max ) . OUTCOME The primary outcome will be changed in plasma CRP concentration . Secondary outcomes include visceral adiposity , the cytokines IL-6 and TNF-alpha , and heart rate variability ( HRV ) in order to examine potential biological mechanisms whereby exercise might affect CRP concentrations . SUMMARY INFLAME will help us underst and the effects of moderate-to-vigorous exercise on CRP concentrations in sedentary individuals . To our knowledge this will be the largest training study specifically design ed to examine the effect of exercise on CRP concentrations . This study has the potential to influence therapeutic applications since CRP measurement is becoming an important clinical measurement in Coronary Heart Disease risk assessment . This study will also contribute to the limited body of literature examining the effect of exercise on the variables of visceral adiposity , cytokines , and heart rate variability BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; 
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EVIDENCE SYNTHESIS As evidence of the exercise resistance premise , we and others found that supervised exercise training results in substantial response variations in glucose homeostasis , insulin sensitivity , and muscle mitochondrial density , wherein approximately 15 - 20 % of individuals fail to improve their metabolic health with exercise .
Classic genetic studies have shown that the extent of the  exercise training  response is largely heritable , whereas new evidence demonstrates that DNA hypomethylation is linked to the exercise response in skeletal muscle .
DNA sequence variation and /or epigenetic modifications may , therefore , dictate the exercise training response .