insulin resistance ( ir ) is an independent predictor for the development of hypertension , coronary heart disease , stroke , cancer , and type 2 diabetes , and greater insulin sensitivity is a protective factor against these clinical conditions .
in addition to obesity and genetic predisposition , poor cardiovascular fitness ( cvf ) is an important independent risk factor for ir .
poor cvf increases a person 's risk for cardiovascular disease , hypertension , and type 2 diabetes     [ 46 ] , and improved cvf attenuates the morbidities associated with obesity .   as a result , active yet overweight individuals can have lower risk for type 2 diabetes and cardiovascular disease than sedentary normal - weight individuals     [ 7 , 8 ] .
thus , an important public health goal is the improvement of cvf in the population in general , not just obese persons .
unfortunately , the current gold standard for assessing cvf , maximal oxygen consumption treadmill or bike testing ( vo2   max ) , requires specialized equipment , time , and expert supervision , and is therefore not practical for evaluation of large groups of children in school or community settings . to expand the ability to identify children with ir , a feasible school - based test of childhood cvf shown to be predictive of ir is needed .
fitnessgram , developed in 1982 by the cooper institute , is a validated battery of tests that can be used to assess childhood physical fitness in schools .  
the progressive aerobic cardiovascular endurance run ( pacer ) is a component of the fitnessgram   and consists of a multistage progressive 20-meter shuttle test ( 20mst ) .  
although laboratory - based fitness assessment ( vo2   max ) has been shown to be predictive of ir , it is not known if a school - based fitness assessment such as the pacer is sufficiently accurate to be predictive of ir .  
the objectives of this study are ( 1 ) determine the predictive value of the pacer , alone and controlled for body composition , for ir ; ( 2 ) compare  school - based  and  laboratory - based  assessments of childhood fitness and body composition in terms of predicting ir .
children ( n = 82 ) from two local middle schools participated in this study .   over a 12-month period ( fall of 2006 to fall of 2007 ) , each participant underwent testing at the university of wisconsin exercise science laboratory after an overnight fast .  
the procedures were approved by the human subjects committee , and informed written consent was obtained before initiating the testing protocol .  
testing included a physical examination , blood work , body composition assessment , and cvf assessment .   within 14 days of this testing
percent body fat ( % bf ) and lean body mass ( lbm ) were measured by dual - energy x - ray absorptiometry ( dxa ) .
whole body scans were performed with the norland xr-36 whole body bone densitometer ( norland corporation , ft .
atkinson , wi ) following standard calibration , and tissue masses were analyzed with software version 3.7.4/2.1.0 .
weight was measured on a calibrated beam balance platform scale to the nearest 0.1 kg .  
 obese  was defined as a bmi      95th percentile for age and gender .
the gold standard cvf assessment was maximal oxygen consumption ( vo2   max ) , determined by open - circuit spirometry using a progressive treadmill walking protocol to volitional fatigue with a medical graphics cpx - d treadmill ( st .
paul , mn ) .   the speed of the treadmill was set initially per the subject 's comfort , starting at 0% grade and increasing   2% every minute .  
requirements to strictly define whether subjects reached their maximal oxygen consumption by this protocol included at least 2 of the following three criteria : ( 1 ) maximal heart rate   > 200 beats per minute ; ( 2 ) respiratory exchange ratio ( vco2/vo2 )   >   1 ; and ( 3 ) a plateau in oxygen consumption .  
all of the children included in the data analysis met at least 2 of the 3 criteria .  
vo2   max can be expressed as vo2 max per kg of total body weight ( vo2 max / kg ) or as vo2 max per kg of lbm ( vo2 max / kglbm ) .  
since the best measurement of fitness is still debated , we analyze our data using both measures of cvf .
homair   is a validated equation that adjusts the fasting insulin and glucose to provide a reliable assessment of insulin resistance , particularly in obese children and adolescents     [ 10 , 11 ] . in children ,
homair   was calculated with the formula : fasting insulin ( iu / ml )      fasting glucose ( mmol / l)/22.5 .  
fasting insulin concentration was determined with the chemiluminescent assay ( arup laboratories , salt lake city , ut ) , and glucose concentration was determined by an enzymatic method ( beckman diagnostics , fullerton , ca ) .   according to arup laboratories , at a mean insulin level of 14.8 iu / ml , the standard deviation of the insulin assay is 1 and the coefficient of variation is 6.7% .
the pacer was conducted by school physical education teachers trained in administering the tests according to the fitnessgram protocol .
subjects run back and forth along a 20-meter course , and each minute the pace required to run the 20 meters increases .
the pace is determined by beeps from a pre - recorded tape or cd .  
the initial running speed is 8.5 km / hour , and the speed increases by 0.5 km / h every minute .
the test is finished when the subject fails to complete the 20-meter run in the allotted time twice . because the number of laps per minute increases as the running speed increases , the pacer results are  scored  as number of laps successfully completed .  
the pacer results were also analyzed using running speed at the last completed one - minute stage and the estimated vo2 max / kg using the leger et al .
the leger equation is   estimated vo2 max / kg = 31.025 + 3.238 ( running speed in km / hr )  3.248 ( age in years ) + 0.1536 ( running speed      age ) . in the regression analysis ,
body composition , fitness , and insulin resistance measurements were summarized by standard descriptive statistics in terms of mean      sd .  
the comparisons of all continuous measurements between subgroups ( males versus females ) were performed using a two - sample t - test or nonparametric wilcoxon rank sum test , when data were not normally distributed .
the univariate associations between fitness and body composition variables and homair   were examined with the nonparametric spearman rank correlation analysis .
multivariate linear regression analysis was performed for both a school - based model ( with pacer as a measure of fitness and bmi z score as a measure of body composition ) and a laboratory - based model ( with vo2 max / kglbm as a measure of fitness and % bf by dxa as a measure of body composition ) to assess the independent contributions of fitness and body composition on insulin resistance .  
the homair   was log - transformed in the regression analyses to meet the assumption of normality .
variance inflation factors were calculated for each multivariate regression model in order to assess for collinearity .
the predictive power of the regression models was assessed by performing cross - validation analysis .  
cross - validation studies were conducted by randomly selecting sub - datasets which were used to fit the model and then validated on the remaining data .
this was repeated 1000 times , and the root mean square error ( rmse ) across all 1000 replications of the predicted versus observed values was calculated .   a smaller rmse indicates better prediction .  
all statistical analyses were performed with sas software ( version 9.1 ; sas institute , cary , nc ) .  
all p values were 2-sided , and p values   < .05 were considered statistically significant .
subject characteristics are presented in table 1 as mean      sd or number ( percentage ) , and the p value reflects the comparison between males and females .
seventeen of the 34 boys ( 50% ) and 9 of the 48 girls ( 19% ) had a bmi greater than the 95th percentile ( p = .003 ) .  
regardless of how cvf is expressed ( relative to total body weight or lean body mass ) , boys had a higher cvf than girls .  
girls had a higher fasting glucose level than boys ( 95.3 versus 93.8 , p = .007 ) , but no significant difference was seen between boys and girls in the fasting insulin or homair .
the pacer correlated significantly and closely with vo2   max / kg ( rs = 0.83 , 95% ci 0.74 to 0.93 , p < .001 ; figure 1 ) .
the pacer also correlated significantly with vo2   max / kglbm ( rs = 0.55 , 95% ci 0.37 to 0.68 , p < .001 ) . since previous validation studies have compared the pacer to vo2   max , and not to vo2   max / kglbm , we used vo2   max / kg for the additional correlations between the pacer and cvf .   in the 26 obese children with a bmi greater than the 95th percentile , the pacer was highly correlated with vo2   max / kg ( rs = 0.74 , 95% ci 0.49 to 0.87 , p < .001 ) . the pacer test result has been expressed in multiple ways in the literature .  
vo2   max / kg correlated strongly with both the running speed ( km / hr ) at the last completed one - minute pacer stage ( rs = 0.83 , 95% ci 0.740.88 , p < .001 ) and the estimated vo2   max / kg ( rs = 0.83 , 95% ci 0.750.89 , p < .001 ) .   therefore , regardless of how the pacer is expressed ( laps , running speed , or estimated vo2   max ) , there was a strong correlation between the pacer and laboratory - based cvf assessment . 

table 2 shows the results of the univariate analysis between homair   and all the variables of interest .  
the pacer was significantly negatively correlated with homair   ( rs =   0.60 , 95% ci   0.75 to   0.44 , p < .001 ; figure 2 ) .  
laboratory - based fitness assessments and the body composition assessments were also significantly and strongly correlated with homair .   an analysis using fasting insulin as the dependent variable revealed virtually identical results ( data not shown ) , and therefore we focused additional analyses on homair   only .
we used multivariate regression analysis to assess various measurements of fitness and body composition with homair   as the dependent variable ( table 3 ) .
model 1 utilized laboratory - based measurements of fitness ( vo2   max / kglbm by maximal treadmill testing ) and body composition ( % bf by dxa ) on insulin resistance ( homair ) .   since more recent studies investigating the relationship between cvf and ir used vo2   max / kglbm , we use vo2   max / kglbm as the measure of fitness in the multivariate regression analysis .  
when we used vo2   max / kg as the measure of fitness , there was no difference in the results ( data not shown ) .  
the laboratory - based method ( model 1 ) accounted for 57% of the variance in homair .   both vo2   max / kglbm ( p < .001 ) and % bf ( p <
.   model 2 utilized school - based measurements of fitness ( pacer ) and body composition ( bmi z score ) on the homair .
the pacer and bmi z score were significant independent predictors of homair ,   with slope parameters of   0.012 ( p = .005 ) and 0.201 ( p < .001 ) , respectively . in both multivariate regression models ,
the variance inflation factors were less than 2.5 , which indicate that colinearity did not confound the results .
the ability of the models to predict ir can be compared with the rmse ( a smaller rmse indicates greater predictive value ) .   the laboratory - based assessment of fitness and body composition ( model 1 ) had a slightly lower rmse of 1.42 compared to an rmse of 1.49 for the school - based assessment ( model 2 )
.   both models had greater predictive value than using bmi z score alone ( rmse of 1.59 ) .  
percent body fat , as determined by a dxa scan , had an rmse of 1.47 .
given that cvf is an important predictor of cardiovascular and metabolic health problems independent of weight , a method to accurately and feasibly assess childhood fitness levels in addition to bmi in larger school - based or population - based studies is needed .  
while a school- or field - based test by definition is easier to use in community settings , the value of school - based assessments of fitness is greatly enhanced if they have been shown to have predictive value for other health outcomes , such as ir .  
this study shows that the pacer is a valid school - based test of cvf and is predictive of ir , independent of body composition .  
moreover , the combination of school - based measurements of both childhood fitness ( pacer ) and fatness ( bmi z score ) predicts ir to a degree similar to laboratory - based measurements of fitness ( vo2   max / kglbm by maximal treadmill testing ) and fatness ( % bf by dxa ) .
thus , the pacer can be used to translate findings of laboratory - based studies to large population - based settings to identify children with low fitness levels and/or increased risk for ir .   to our knowledge
, this study is the first to identify a correlation between a school - based fitness test in children and measurements of ir .
this study showed that cvf , measured either by a laboratory - based or a school - based assessment , is an important predictor of insulin resistance , independent of fatness .  
some previous studies have shown that   laboratory - based   assessment of fitness in children has a highly significant correlation with ir after controlling for body composition     [ 3 , 1317 ] , while others have not     [ 1820 ] .
a previous study by our group found that vo2   max / kglbm ( by maximal treadmill testing ) was significantly correlated with homair   ( r =   0.42 ) . in the present study ,
the laboratory - based assessment of fitness was a significant independent predictor of ir .  
the new contribution of this study is the correlation of   school - based    fitness tests in children with measures of ir .  
the pacer correlated very closely and significantly with homair   ( rs =    0.60 ) , and after controlling for body composition , the pacer was still independently predictive of ir ( model 2 , table 3 ) .
we compared a laboratory - based method to a school - based method of predicting insulin resistance using multivariate regression analysis .  
model 1 utilized laboratory - based assessments of fitness and body composition while model 2 included school - based assessments of fitness and body composition .  
the laboratory - based model had an rmse of 1.42 compared to 1.49 in the school - based model ( a smaller rmse indicates better prediction ) .
it can be reasonably argued that this small difference in predictive value is counterbalanced by the ability to administer the school - based tests to a much larger population of children .  
another valid question is whether assessment of fitness adds substantial value to simply measuring and tracking obesity .
the rmse for bmi z score is 1.59 ( table 2 ) , compared to 1.49 for model 2 .  
weight - only  model would not capture the many benefits of fitness testing and fitness promotion that extend beyond the prediction of ir     [ 4 , 21 , 22 ] .
it is interesting to note that the scatterplot comparing pacer results to homair   ( figure 2 ) shows high variability in ir at low fitness levels , and progressively less variability as the fitness levels improve .  
this could indicate that the increased ir variability at low fitness levels reflects individual genetic predispositions for obesity - induced ir , and that higher fitness levels can improve insulin sensitivity in all persons .  
our group has previously shown that increasing fitness levels in middle school children can lead to improvements in fasting insulin levels , and the effect of improved fitness on ir and the risk for type 2 diabetes has been a consistent finding in adults [ 4 , 8 ] . in this cross - sectional study , the effect of improved fitness levels on ir can not be determined .
the homair   is a useful approximation of insulin resistance measured by euglycemic clamp studies , but does have a degree of error compared with that gold standard .  
additionally , puberty can increase insulin resistance and may be a confounding variable in the relationship between fitness testing and ir .  
finally , our multivariate models did not include family history of type 2 diabetes , which would likely improve the prediction of ir by accounting for a child 's genetic predisposition for ir .  
future studies hope to incorporate family history in order to improve the predictive value of school - based assessments for ir .
the relative contributions of fitness and fatness to the development of ir continue to be debated , and this study was not designed to address that issue .  
regardless of their relative importance , it is clear that improvements in both fitness and fatness will yield important health consequences for increasingly obese and sedentary children .
thus , it is essential to develop interventions to reduce insulin resistance that are applicable to the  real world  of children .  
these interventions will need a field - based metric that can be easily and broadly implemented to translate exercise laboratory study findings to the public health setting .
with rates of both obesity and poor fitness increasing in children , development of ir will put increasing numbers of children at risk of developing early metabolic and cardiovascular disease .  
precise measurement of ir involves blood studies of insulin levels required to maintain euglycemia after glucose administration ( euglycemic clamp study ) , an impractical procedure in school or community settings .
laboratory - based prediction of ir , through measurement of cvf ( by maximal treadmill testing ) and body composition ( by dxa ) , is also resource intensive and impractical in nonlaboratory settings .
this study shows that ( 1 ) the pacer is a valid school - based test of cvf and is predictive of ir ; ( 2 ) simple measures of both childhood fitness ( pacer ) and body composition ( bmi z score ) together accurately predict ir to a greater degree than bmi alone , approximating the degree of prediction from logistically complex and expensive laboratory tests of fitness and body composition .
thus , the pacer offers a valid school - based test of cvf that is predictive of ir and allows findings from exercise laboratory studies to be translated to a school or community setting .
 
 objectives . ( 1 ) determine the predictive value of a school - based test of cardiovascular fitness ( cvf ) for insulin resistance ( ir ) ; ( 2 ) compare a  school - based  prediction of ir to a  laboratory - based  prediction , using various measures of fitness and body composition . methods . 
 middle school children ( n = 82 ) performed the progressive aerobic cardiovascular endurance run ( pacer ) , a school - based cvf test , and underwent evaluation of maximal oxygen consumption treadmill testing ( vo2 max ) , body composition ( percent body fat and bmi z score ) , and ir ( derived homeostasis model assessment index 
 [ homair ] ) . 
 
 results . 
 pacer showed a strong correlation with vo2 max / kg ( rs = 0.83 , p < .001 ) and with homair ( rs =   0.60 , p < .001 ) . 
 multivariate regression analysis revealed that a school - based model ( using pacer and bmi z score ) predicted ir similar to a laboratory - based model ( using vo2 max / kg of lean body mass and percent body fat ) . conclusions . 
 the pacer is a valid school - based test of cvf , is predictive of ir , and has a similar relationship to ir when compared to complex laboratory - based testing . 
 simple school - based measures of childhood fitness ( pacer ) and fatness ( bmi z score ) could be used to identify childhood risk for ir and evaluate interventions . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions