the design and methods of this multicenter , randomized controlled trial have been detailed elsewhere ( 8,20 ) and will be briefly reported here . locally appointed ethics committees approved the research protocol , and participants gave written informed consent .
the ides involved 22 outpatient diabetes clinics throughout italy between october 1 , 2005 , and march 31 , 2006 .
each center was connected with a metabolic fitness center , a dedicated facility where patients trained under the supervision of an exercise professional .
sedentary patients with type 2 diabetes , according to the definition of the american diabetes association ( 21 ) and who fulfilled the international diabetes federation criteria for the metabolic syndrome ( 22 ) , were eligible for this study .
of the 691 eligible patients , 85 were excluded for various reasons and 606 were recruited and randomized to supervised training plus structured exercise counseling ( exe group ; n = 303 ) versus a control group that received counseling alone as part of standard care ( con group ; n = 303 ) for 12 months .
randomization was stratified by center and , within each center , by age ( < 60 vs. 60 years ) and type of diabetes treatment ( diet with or without oral agents vs. insulin ) using permuted - block randomization software .
physicians and patients were not blinded to group assignment , whereas sample blinding at the central laboratory was achieved using bar codes .
subjects from both groups received structured , individualized counseling ( 23 ) aimed at achieving the currently recommended amount of pa ( 24 ) by encouraging any type of commuting , occupational , home , and leisure - time pa .
the training program for the exe group consisted of 150 min / week in two supervised sessions of progressive mixed ( aerobic and resistance ) training ( 8,20 ) .
aerobic training was performed at 5570% of predicted vo2max using a treadmill , step , elliptical , arm , or cycle - ergometer .
the exercise load for the equipment was calculated to achieve prescribed exercise intensity , expressed as percentage of vo2max , by the use of standard equations ( 25 ) .
resistance training was performed at 6080% of predicted 1 repetition maximum ( 1-rm ) and consisted of four resistance exercises , comprising a thrust movement on the transverse plane ( chest press or equivalent ) , traction movement on the frontal plane ( lateral pull down or equivalent ) , squat movement ( leg press or equivalent ) , trunk flexion for the abdominals , and three stretching positions .
intensity was adjusted according to improvements in predicted vo2max and 1-rm , as recorded throughout the study .
in addition , caloric expenditure was increased progressively by 0.1-kcal / kg body weight / session every month .
standard care consisted of a treatment regimen aimed at achieving optimal glycemic , lipid , blood pressure ( bp ) , and body weight targets , as established by current guidelines , and including diet prescription and glucose- , lipid- , and bp - lowering agents , as needed ( 8,20 ) . for ethical reasons and to test the real - world applicability of the ides results , the treatment regimen was adjusted according to results of biochemical tests performed locally at 3-month intervals , and changes in type , number , and dosage of drugs were recorded .
secondary outcomes included improvements in other modifiable cvd risk factors , change in the number and/or dosage of glucose- , lipid- , and bp - lowering drugs , uk prospective diabetes study ( ukpds ) global chd 10-year risk scores , health - related quality - of - life , and the relationship between changes in physical fitness and modifiable cvd risk factors .
results of this trial have been reported elsewhere ( 8,9 ) , except those concerning the relation of physical fitness with modifiable cvd risk factors . at baseline ,
the volume of pa was assessed retrospectively using the minnesota leisure time physical activity questionnaire ( 26 ) .
the amount of pa was evaluated prospectively by asking patients to fill in a daily diary based on the range of activities considered in this questionnaire .
volume was calculated by multiplying the metabolic equivalent ( met ) scores corresponding to each minnesota code ( 8) , by time in hours per week spent in each activity , and expressed as mets  h  week . for aerobic exercise , energy expenditure during supervised sessions was calculated automatically by the machines from workload ( i.e. , the combination of speed and slope for treadmill , steps per minute for step and power for ergometer ) , using standard equations ( 25 ) . for resistance exercise , a conservative estimate of 3 mets  h was established , based on direct measurements in subjects with type 2 diabetes ( 27 ) .
the following modifiable cvd risk factors were evaluated at baseline and end - of - study : hba1c , fasting blood glucose and serum insulin , waist circumference , bmi , bp , triglycerides , total and hdl cholesterol , and high - sensitivity c - reactive protein ( hs - crp ) .
biochemical tests were performed at the central laboratory , at baseline , and end - of - study , and locally , throughout the study period , to adjust treatment regimen ( 8,20 ) . the homeostasis model assessment - insulin resistance ( homa - ir ) index
was calculated by the formula : homa - ir = [ insulin ( in pmol / l )  fpg ( in mmol / l)]/156.3 , whereas ldl cholesterol was estimated by the equation : ldl cholesterol ( in mmol / l ) = total cholesterol  [ hdl cholesterol + ( triglycerides/2.17 ) ] , as previously reported ( 20 ) .
global chd 10-year risk scores were calculated using the ukpds risk engine ( 28 ) .
parameters of physical fitness ( i.e. , cardiorespiratory fitness , strength , and flexibility ) were evaluated at baseline , end - of - study , and in the exe group , also during the study period , to adjust training loads ( 8,20 ) .
assessment of cardiorespiratory fitness consisted of a submaximal vo2max evaluation , ( i.e. , at 80% of the predicted maximal heart rate [ = 220  age ] ) .
it was preferred to a maximal test , because 1 ) the latter can not be performed without a cardiologist , according to italian law ; and 2 ) heart rate varies linearly with vo2 to the point of maximum exertion , thus allowing extrapolation of the actual vo2max value .
the test was preceded by two consecutive run - in sessions to become familiar with testing devices and protocols .
all patients performed the test at the treadmill , which was preferred to the cycloergometer to avoid early muscle exhaustion in untrained subjects , using a protocol modified form the balke and ware procedure ( 29 ) .
indirect calorimetry was used to measure vo2 by the use of a gas exchange analyzer ( fitmate , cosmed , rome , italy ) , with concurrent assessment of heart rate . for patients taking medications that affect heart rate , such as -adrenergic blockers , the borg rate of perceived exertion scale was used ( version 110 ) .
patients were stopped at the perceived value of 56 ( hard ) , corresponding to a heart rate of 7089% ( 30 ) .
for strength assessment , a test was performed with the following modalities : thrust movement on the transverse plane ( chest press or equivalent ) , traction movement on the frontal plane ( lateral pull down or equivalent ) , and squat movement ( leg press or equivalent ) .
although the 1-rm test is the most reliable test for evaluating the maximal dynamic strength of a muscle or group of muscles , because of the very low fitness profile of patients enrolled in this study , a 58 maximal repetition test was preferred , for safety ( to avoid maximal loads to the joint structures ) and validity ( untrained subjects are not always able to properly reach their 1-rm ) reasons . then , 1-rm was predicted from the weight loaded and the number of repetitions executed after a proper warm up using the brzycki equation ( 31 ) .
results were expressed as upper body ( average of chest press and lateral pull down ) and lower body ( leg press ) strength .
a standard bending test was executed to assess hip and truck flexibility ( 8,20 ) .
patients stood on a step with legs fully extended and were asked to bend the torso forward to try to touch the ground with their fingertips .
the test was performed three times , and the distance between the finger and the ground was measured by the exercise specialist at the third attempt .
baseline to end - of - study changes ( expressed as median and interquartile range [ iqr ] ) in total pa , cvd risk factors , and total chd risk score were calculated by quintiles of changes in physical fitness parameters ( i.e. , vo2max and upper and lower body strength and flexibility ) and analyzed using kruskal - wallis one - way anova . a test for linear trend was also applied .
a value of p < 0.05 was considered statistically significant . to encompass the entire range of fitness values , the whole cohort of 606 patients
to assess whether improvements in fitness predicted changes from baseline in hba1c , other cvd risk factors , and chd risk score , independently of body weight loss , multiple regression analyses were applied , with baseline to end - of - study changes in each modifiable cvd risk factor as a dependent variable .
covariates were the baseline value of each cvd risk factor , the change in each fitness parameter ( and , for upper and lower body strength and flexibility , also in vo2max ) , change in bmi , body weight , or waist circumference to assess dependence on body weight loss , and study arm , to account for the independent effect of intervention .
additional regression analyses were performed with pa / exercise volume as the covariate forced in the model or , to account for change in medication throughout the 12-month period , with treatment at baseline and treatment initiation during the study included in the model as dichotomous ( yes vs. no ) variables .
the ides involved 22 outpatient diabetes clinics throughout italy between october 1 , 2005 , and march 31 , 2006 . each center was connected with a metabolic fitness center , a dedicated facility where patients trained under the supervision of an exercise professional .
sedentary patients with type 2 diabetes , according to the definition of the american diabetes association ( 21 ) and who fulfilled the international diabetes federation criteria for the metabolic syndrome ( 22 ) , were eligible for this study .
of the 691 eligible patients , 85 were excluded for various reasons and 606 were recruited and randomized to supervised training plus structured exercise counseling ( exe group ; n = 303 ) versus a control group that received counseling alone as part of standard care ( con group ; n = 303 ) for 12 months .
randomization was stratified by center and , within each center , by age ( < 60 vs. 60 years ) and type of diabetes treatment ( diet with or without oral agents vs. insulin ) using permuted - block randomization software .
physicians and patients were not blinded to group assignment , whereas sample blinding at the central laboratory was achieved using bar codes .
subjects from both groups received structured , individualized counseling ( 23 ) aimed at achieving the currently recommended amount of pa ( 24 ) by encouraging any type of commuting , occupational , home , and leisure - time pa .
the training program for the exe group consisted of 150 min / week in two supervised sessions of progressive mixed ( aerobic and resistance ) training ( 8,20 ) .
aerobic training was performed at 5570% of predicted vo2max using a treadmill , step , elliptical , arm , or cycle - ergometer .
the exercise load for the equipment was calculated to achieve prescribed exercise intensity , expressed as percentage of vo2max , by the use of standard equations ( 25 ) .
resistance training was performed at 6080% of predicted 1 repetition maximum ( 1-rm ) and consisted of four resistance exercises , comprising a thrust movement on the transverse plane ( chest press or equivalent ) , traction movement on the frontal plane ( lateral pull down or equivalent ) , squat movement ( leg press or equivalent ) , trunk flexion for the abdominals , and three stretching positions .
intensity was adjusted according to improvements in predicted vo2max and 1-rm , as recorded throughout the study .
in addition , caloric expenditure was increased progressively by 0.1-kcal / kg body weight / session every month .
standard care consisted of a treatment regimen aimed at achieving optimal glycemic , lipid , blood pressure ( bp ) , and body weight targets , as established by current guidelines , and including diet prescription and glucose- , lipid- , and bp - lowering agents , as needed ( 8,20 ) . for ethical reasons and to test the real - world applicability of the ides results , the treatment regimen was adjusted according to results of biochemical tests performed locally at 3-month intervals , and changes in type , number , and dosage of drugs were recorded .
secondary outcomes included improvements in other modifiable cvd risk factors , change in the number and/or dosage of glucose- , lipid- , and bp - lowering drugs , uk prospective diabetes study ( ukpds ) global chd 10-year risk scores , health - related quality - of - life , and the relationship between changes in physical fitness and modifiable cvd risk factors .
results of this trial have been reported elsewhere ( 8,9 ) , except those concerning the relation of physical fitness with modifiable cvd risk factors . at baseline ,
the volume of pa was assessed retrospectively using the minnesota leisure time physical activity questionnaire ( 26 ) .
the amount of pa was evaluated prospectively by asking patients to fill in a daily diary based on the range of activities considered in this questionnaire .
volume was calculated by multiplying the metabolic equivalent ( met ) scores corresponding to each minnesota code ( 8) , by time in hours per week spent in each activity , and expressed as mets  h  week . for aerobic exercise , energy expenditure during supervised sessions was calculated automatically by the machines from workload ( i.e. , the combination of speed and slope for treadmill , steps per minute for step and power for ergometer ) , using standard equations ( 25 ) . for resistance exercise , a conservative estimate of 3 mets  h was established , based on direct measurements in subjects with type 2 diabetes ( 27 ) .
the following modifiable cvd risk factors were evaluated at baseline and end - of - study : hba1c , fasting blood glucose and serum insulin , waist circumference , bmi , bp , triglycerides , total and hdl cholesterol , and high - sensitivity c - reactive protein ( hs - crp ) .
biochemical tests were performed at the central laboratory , at baseline , and end - of - study , and locally , throughout the study period , to adjust treatment regimen ( 8,20 ) . the homeostasis model assessment - insulin resistance ( homa - ir ) index
was calculated by the formula : homa - ir = [ insulin ( in pmol / l )  fpg ( in mmol / l)]/156.3 , whereas ldl cholesterol was estimated by the equation : ldl cholesterol ( in mmol / l ) = total cholesterol  [ hdl cholesterol + ( triglycerides/2.17 ) ] , as previously reported ( 20 ) .
global chd 10-year risk scores were calculated using the ukpds risk engine ( 28 ) .
parameters of physical fitness ( i.e. , cardiorespiratory fitness , strength , and flexibility ) were evaluated at baseline , end - of - study , and in the exe group , also during the study period , to adjust training loads ( 8,20 ) .
assessment of cardiorespiratory fitness consisted of a submaximal vo2max evaluation , ( i.e. , at 80% of the predicted maximal heart rate [ = 220  age ] ) .
it was preferred to a maximal test , because 1 ) the latter can not be performed without a cardiologist , according to italian law ; and 2 ) heart rate varies linearly with vo2 to the point of maximum exertion , thus allowing extrapolation of the actual vo2max value .
the test was preceded by two consecutive run - in sessions to become familiar with testing devices and protocols .
all patients performed the test at the treadmill , which was preferred to the cycloergometer to avoid early muscle exhaustion in untrained subjects , using a protocol modified form the balke and ware procedure ( 29 ) .
indirect calorimetry was used to measure vo2 by the use of a gas exchange analyzer ( fitmate , cosmed , rome , italy ) , with concurrent assessment of heart rate . for patients taking medications that affect heart rate , such as -adrenergic blockers , the borg rate of perceived exertion scale was used ( version 110 ) .
patients were stopped at the perceived value of 56 ( hard ) , corresponding to a heart rate of 7089% ( 30 ) . for strength assessment ,
a test was performed with the following modalities : thrust movement on the transverse plane ( chest press or equivalent ) , traction movement on the frontal plane ( lateral pull down or equivalent ) , and squat movement ( leg press or equivalent ) .
although the 1-rm test is the most reliable test for evaluating the maximal dynamic strength of a muscle or group of muscles , because of the very low fitness profile of patients enrolled in this study , a 58 maximal repetition test was preferred , for safety ( to avoid maximal loads to the joint structures ) and validity ( untrained subjects are not always able to properly reach their 1-rm ) reasons . then , 1-rm was predicted from the weight loaded and the number of repetitions executed after a proper warm up using the brzycki equation ( 31 ) .
results were expressed as upper body ( average of chest press and lateral pull down ) and lower body ( leg press ) strength .
a standard bending test was executed to assess hip and truck flexibility ( 8,20 ) .
patients stood on a step with legs fully extended and were asked to bend the torso forward to try to touch the ground with their fingertips .
the test was performed three times , and the distance between the finger and the ground was measured by the exercise specialist at the third attempt .
baseline to end - of - study changes ( expressed as median and interquartile range [ iqr ] ) in total pa , cvd risk factors , and total chd risk score were calculated by quintiles of changes in physical fitness parameters ( i.e. , vo2max and upper and lower body strength and flexibility ) and analyzed using kruskal - wallis one - way anova . a test for linear trend was also applied .
a value of p < 0.05 was considered statistically significant . to encompass the entire range of fitness values ,
the whole cohort of 606 patients was considered . to assess whether improvements in fitness predicted changes from baseline in hba1c , other cvd risk factors , and chd risk score , independently of body weight loss , multiple regression analyses were applied , with baseline to end - of - study changes in each modifiable cvd risk factor as a dependent variable .
covariates were the baseline value of each cvd risk factor , the change in each fitness parameter ( and , for upper and lower body strength and flexibility , also in vo2max ) , change in bmi , body weight , or waist circumference to assess dependence on body weight loss , and study arm , to account for the independent effect of intervention .
additional regression analyses were performed with pa / exercise volume as the covariate forced in the model or , to account for change in medication throughout the 12-month period , with treatment at baseline and treatment initiation during the study included in the model as dichotomous ( yes vs. no ) variables .
subjects from the ides cohort had a mean age of 58.8 years ( sd 8.5 ) , a median diabetes duration of 6 years ( iqr 310 ) , and a male - to - female ratio of 58/42 .
baseline values for vo2max , upper and lower body strength , and flexibility were 25.9  6.2 ml / kg / min , 40.0  16.6 kg , 107.3  68.5 kg , and 11.7  9.8 cm , respectively .
as previously reported ( 8) , the median attendance of the supervised exercise sessions in the exe group was 80.3% ( iqr , 7599% ) .
moreover , vo2max ( mean difference 2.8 ml / kg / min [ 95% ci 2.13.5 ] , p < 0.001 ) and flexibility ( 4.6 cm [ 5.7 to 3.6 ] ) improved more markedly in exe than in con subjects , whereas upper ( 11.0 kg [ 9.512.5 ] ) and lower ( 30.8 kg [ 25.135.6 ] ) body strength increased significantly only in exe participants ( 8) ( supplementary fig .
changes in vo2max , and upper and lower body strength ( tables 1 , 2 , and 3 ) were significantly and linearly associated with variation in pa volume , hba1c , bmi , waist circumference , hs - crp , total chd risk score , and , inversely , with change in hdl cholesterol .
in addition , flexibility was significantly associated with these parameters ( p < 0.0001 for trend ) , except for hba1c ( p = 0.003 ) and hs - crp ( p = 0.041 ; data not shown ) .
less significant associations were found for vo2max with insulin and homa - ir , for upper body strength with ldl cholesterol , and for lower body strength with insulin , homa - ir , and total and ldl cholesterol .
associations with insulin and homa - ir remained after excluding the 73 individuals on insulin treatment , which significantly influences these parameters . baseline to end - of - study changes ( median and iqr ) in pa volume , cvd risk factors , and total chd risk score by quintiles of vo2max baseline to end - of - study changes ( median and iqr ) in pa volume , cvd risk factors , and total chd risk score by quintiles of upper body strength baseline to end - of - study changes ( median and iqr ) in pa volume , cvd risk factors , and total chd risk score by quintiles of lower body strength regression analyses ( table 4 ) showed that changes in vo2max predicted a reduction in hba1c , waist circumference , hs - crp , and total chd ukpds risk score , and an increase in hdl cholesterol , independently of study arm and change in bmi .
in addition , changes in upper body strength predicted improvements in hba1c , waist circumference , hs - crp , and total chd risk score , whereas an increase in lower body strength predicted only amelioration of hs - crp , independently of study arm , and changes in bmi and vo2max . when changes in bmi and vo2max were excluded from the model , lower body strength
was also significantly associated with waist circumference reduction ( p = 0.039 ) . finally , improved flexibility predicted changes in waist circumference and hdl cholesterol , again independently of study arm , and changes in bmi and vo2max .
multiple regression analyses of association of baseline to end - of - study changes in physical fitness parameters with variation in selected cvd risk factors and total chd risk score in these analyses , bmi was significantly associated with changes in hba1c , and waist circumference , but not hdl cholesterol , hs - crp , or total ukpds chd risk score , whereas study arm predicted changes in all of these variables with most combinations of fitness components and measures of adiposity as covariates ( data not shown ) .
results were similar when bmi values were substituted for body weight as a covariate in the regression models ( data not shown ) .
in contrast , when waist circumference was included in the model as a measure of adiposity in place of bmi or body weight , an independent association of vo2max and flexibility with cvd risk factors was no longer observed , except for a reduction in hs - crp ( p = 0.017 ) and an increase in hdl cholesterol ( p = 0.018 ) , respectively , whereas strength , particularly upper body , continued to predict hba1c ( p = 0.016 ) , hs - crp ( p = 0.005 ) , and total chd risk score ( p < 0.0001 ) .
finally , all fitness parameters no longer predicted changes in cvd risk factors when pa / exercise volume was forced in the model , whereas associations remained significant when change in medication was included as a covariate .
this report shows that pa / exercise - induced improvements in physical fitness , particularly in cardiorespiratory fitness and upper body strength , significantly predict changes in several modifiable cvd risk factors and in the total ukpds chd 10-year risk score , independently of study arm , change in bmi or body weight , and , in case of strength , also of vo2max and waist circumference .
a previous meta - analysis of small - sized studies showed that structured aerobic exercise training improves cardiorespiratory fitness in subjects with type 2 diabetes , along with a reduction of hba1c ( 32 ) .
moreover , cardiorespiratory and/or muscular fitness correlated with changes in hba1c in sedentary diabetic individuals performing supervised aerobic and/or resistance training ( 33 ) .
our data indicate for the first time that in these subjects , pa / exercise - induced amelioration of physical fitness is linked to improvements in a wide range of modifiable cvd risk factors in addition to hba1c , thus resulting in a significantly reduced estimated total chd 10-year risk .
these factors included waist circumference , insulin , homa - ir , hdl cholesterol , and hs - crp , which are the metabolic and inflammatory abnormalities related to central fat distribution in subjects with type 2 diabetes and the metabolic syndrome ( 34 ) .
interestingly , waist circumference and homa - ir were also independent predictors of hba1c reduction in the ides participants ( 8) .
taken together , these observations are consistent with the inverse association of cardiorespiratory fitness with the prevalence of type 2 diabetes ( 35 ) and the metabolic syndrome ( 36 ) as well as of low levels of pa with traditional and nontraditional cvd risk factors ( 37 ) in the general population .
a very important finding of our study is that the relationship of changes in physical fitness with improvements in modifiable cvd risk factors was independent of body weight loss , although fitness correlated significantly with bmi and waist circumference .
this observation , which is consistent with the lack of interaction between fitness and fatness ( 38 ) , supports the concept that fitness ameliorates the unfavorable cvd risk factor profile driven by increased adiposity through mechanisms independent , at least partly , of weight loss .
these mechanisms seem to involve enhanced muscle fuel supply and storage , which increase insulin sensitivity ( 33 ) , as well as production of myokines , which act locally in a paracrine fashion and also as hormones in other organs of the body , including fat , to improve metabolism and reduce inflammation ( 39 ) . a role for muscle independent of central fat distribution
is strongly supported by the observation that muscular fitness , at variance with cardiorespiratory fitness , predicted changes in modifiable cvd risk factors even after adjustment for waist circumference , a measure of visceral adiposity .
these findings suggest that lifestyle interventions aimed at reducing cvd risk in subjects with type 2 diabetes should target improvement of fitness , in addition to weight loss , and that strategies including diet plus pa / exercise would be more effective than diet alone at the same level of achieved bmi . in this view , physical fitness may represent a surrogate outcome in these subjects , especially in individuals who struggle to lose weight .
however , although pa is the main determinant of physical fitness , as shown in our study by the strong association between these two parameters and by the disappearance of association between fitness and modifiable cvd risk factors after adjustment for pa / exercise volume , genetic factors also play a role in individuals with the low - fitness phenotype .
it is unclear whether specific pa programs may reverse low - fitness in these subjects and whether those who fail to improve fitness with exercise still receive health benefits from training ( 40 ) .
finally , improvements of cardiorespiratory and muscular fitness appeared to exert at least partly independent effects on modifiable cvd risk factors , according to the observation that relation of strength , particularly upper body , with these parameters remained significant when vo2max and also waist circumference were forced in the model as covariates .
moreover , because the exe subjects followed a supervised mixed ( aerobic and resistance ) training program , whereas the con participants performed predominantly aerobic pa ( 8) , this is also in keeping with the association of study arm with improvements in modifiable cvd risk factors , although relation of fitness with these parameters occurred independently of it .
this supports the finding that , given the same volume of pa , the combination of aerobic and resistance training is more effective than either one alone in reducing cvd risk in subjects with type 2 diabetes ( 6,7 ) and suggests that this is dependent of the concurrent improvement in cardiorespiratory and muscular fitness . strengths of this study are that the ides was multicenter , thus less dependent on local factors , and of a larger size and longer duration than other exercise intervention trials in patients with type 2 diabetes ( 6,7 ) .
a potential limitation of this trial is the unblinded design , although it is impossible to keep assignment to supervised training hidden to both patients and physicians .
in addition , in our study , although patients from both groups received specific dietary prescriptions and adherence to diet was verified at intermediate visits , diet was not considered in the data analysis . in conclusion , this analysis of data from the ides shows that pa / exercise - induced increases in physical fitness predict improvements in cvd risk factors and estimated chd 10-year risk in subjects with type 2 diabetes independently of body weight loss and , for muscular fitness , also of waist circumference reduction .
these findings indicate the need for targeting fitness , particularly muscular , in these individuals , especially in subjects who struggle to lose weight , by implementing specific training programs including resistance exercise .
 objectivephysical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes . here 
 , we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the italian diabetes and exercise study.research design and methodssedentary patients with type 2 diabetes ( n = 606 ) were enrolled in 22 outpatient diabetes clinics and randomized to twice - a - week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months . 
 baseline to end - of - study changes in cardiorespiratory fitness , strength , and flexibility , as assessed by vo2max estimation , a 58 maximal repetition test , and a hip / trunk flexibility test , respectively , were calculated in the whole cohort , and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors.resultschanges in vo2max , upper and lower body strength , and flexibility were significantly associated with the variation in the volume of physical activity , hba1c , bmi , waist circumference , high - sensitivity c - reactive protein ( hs - crp ) , coronary heart disease ( chd ) risk score , and inversely , hdl cholesterol . 
 changes in fitness predicted improvements in hba1c , waist circumference , hdl cholesterol , hs - crp , and chd risk score , independent of study arm , bmi , and in case of strength , also waist circumference.conclusionsphysical activity / exercise - induced increases in fitness , particularly muscular , predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss , thus indicating the need for targeting fitness in these individuals , particularly in subjects who struggle to lose weight . 
RESEARCH DESIGN AND METHODS
Setting and participants
Interventions
Main outcome measures
Statistical analysis
RESULTS
CONCLUSIONS