the anaerobic threshold ( at ) is a hallmark of the aerobic fitness of athletes1 , physically active individuals3 and on a minor scale for special 
 populations , such as individuals with type 2 diabetes ( t2d)2 , 4 , 5 . at has been considered the gold standard along with maximum oxygen 
 consumption ( vo2max ) for the evaluation of aerobic fitness and the subsequent 
 prescription of aerobic exercise6,7,8,9 . moreover , monitoring of aerobic training 
 adaptations through at determination may be especially interesting because no maximal effort 
 is needed , and could be safer for individuals with pathologies such as hypertension and 
 diabetes10 , 11 . for instance , the at has been determined through the analysis of heart rate 
 variability ( hrv)2 , blood 
 catecholamines12 , blood glucose and 
 lactate3 , ventilation and respiratory 
 equivalents13 , 14 , and the double product ( dp)15,16,17,18,19,20,21,22 . identification of at through different indices , such as the double product ( dp ) , has been 
 widely utilized for healthy individuals16 , 17 , 19 , athletes20 and 
 individuals with cardiovascular diseases15 , 16 , 18 . however , few studies have identified the at of individuals with t2d 
 through different methods2 , 23 , while the exercise recommendations for t2d24 indicate that these patients should be 
 encouraged to undertake an exercise test before being submitted to physical training . the at of t2d individuals is often observed to be between 6070% of 
 vo2max6 , 8 , 25 , which is an exercise 
 intensity that has been widely recommended for this population for better blood glucose and 
 cardiovascular control24 . further , previous studies have shown that aerobic exercises performed around at intensities 
 significantly reduced the blood pressure ( bp ) of individuals with t2d in the post - exercise 
 period6,7,8 , 25 , 26 , and none of these 
 previous studies reported complications during the experimental sessions , suggesting the 
 desirability of at identification for this population , since inadequate physical exertion 
 can be a powerful triggering factor of myocardial infarction27 . individuals with t2d often present autonomic dysfunction28,29,30 . compared to healthy individuals , it is therefore likely that they 
 would show a different hemodynamic reaction [ heart rate ( hr ) and bp , and in turn dp ] during 
 exercise , such as an exaggerated exercise blood pressure response31 . in addition , hypertension and t2d very frequently 
 coexist , since 20% of hypertensive patients have t2d , and 80% of people with t2d are 
 hypertensive32 . hypertensiveness , could 
 also affect the hemodynamic responses during exercise , which may in turn complicate at 
 detection through cardiovascular responses . have presented the feasibility of 
 at identification for t2d individuals through hrv analyses2 and kumagai et al . identified the double product breakpoint ( dpbp ) 
 in t2d individuals , but did not compared with any other anaerobic threshold identification 
 method23 . thus , we hypothesized that at 
 could be predicted through the dpbp during exercise performed by t2d individuals , similar to 
 healthy individuals16 . moreover , 
 identification of at through the dpbp would be relevant since the dp can provide information 
 that correlates with myocardial oxygen consumption , which is recognized as a non - invasive 
 indicator of cardiac overload33 , 34 as well as cardiac ischemic events 
 including acute myocardial infarction35 . further , the determination of at through the dpbp is a simple method that does not depend on 
 the use of complex equipment such as gas analyzers , which are expensive and require the use 
 of specialized technicians to operate them . the validity of the dpbp in estimating the at using a sphygmomanometer and stethoscope has 
 not been investigated yet . experiments have used either automated blood pressure 
 monitor15,16,17 , 19 , 20 , 23 or a cannula inserted into the brachial artery18 . these procedures are not accessible to most practioners 
 because they require costly equipment as well as highly invasive procedures . in addition , to 
 the best of our knowledge , no study has examined the dpbp as an estimate of the at in 
 individuals with t2d . thus , the purpose of this study was to verify whether or not the at of t2d individuals can 
 be predicted through the dp method , and to analyze the relationships between the workload 
 ( watts ) , oxygen consumption ( vo2 ) and hr obtained by the dpbp and the ventilatory 
 threshold ( vt ) methods . after approval from the local human research ethics committee ( universidade 
 catlica de braslia : 011/2011 ) , and obtaining the written informed consent of 
 the volunteers , 11 t2d individuals ( 8 females ) , and 10 controls ( 7 females ) were initially 
 selected to participate in this study . exclusion criteria for participation in this study 
 included previous diagnosis of peripheral neuropathy or retinopathy , as well as diabetic 
 foot ulcerations osteomioarticular complications , the endogenous use of insulin , and/or use 
 of medicines that could have directly affected hr or bp . all the individuals were recruited 
 at a public hospital , and all had been previously assessed using standard tests conducted by 
 endocrinologists and cardiologists . two participants with t2d were excluded from the 
 analysis because it was not possible to detect their vt and/or dpbp ( table 1table 1.the number of cases in which the ventilatory threshold ( vt ) and the double 
 product breakpoint ( dpbp ) were detected by all observersparametert2d ( n)nd ( n)totalparticipants initially screened111021vt detected101020dpbp detected91019hr primarily responsible for dpbp112sbp responsible for dpbp549participants included in the analysis91019t2d : individuals with type 2 diabetes ; nd : individuals without t2d ; vt : ventilatory 
 threshold ; dpbp : double product breakpoint ; hr : heart rate ; sbp : systolic blood 
 pressure ) . therefore , the statistical power a priori conferred on this sample ( n=19 ) 
 was 82% ( power=0.82 ) . the t2d individuals were receiving medical treatments of oral 
 hypoglycemiants ( metformin , metformin + glibenclamide ) . the general 
 characteristics of the volunteers are presented in table 2table 2.characteristics of the individuals with type 2 diabetes ( t2d ) and non - diabetic 
 ( nd ) controlst2d ( n=9)nd ( n=10)age ( yrs)63.2  8.958.3  7.8body mass ( kg)70.2  14.172.5  19.2height ( m)1.59  0.11.61  0.11bmi ( kgm)26.3  5.027.1  4.1body fat ( % ) 37.4  5.634.5  7.0hba1c ( % ) 6.8  1.35.2  0.2*vo2peak ( mlkgmin)21.4  3.522.6  5.1maximal heart rate t2d : individuals with type 2 diabetes ; 
 nd : individuals without t2d ; bmi : body mass index ; hba1c : glycated 
 hemoglobin ; * significant difference ( p<0.05 ) . t2d : individuals with type 2 diabetes ; nd : individuals without t2d ; vt : ventilatory 
 threshold ; dpbp : double product breakpoint ; hr : heart rate ; sbp : systolic blood 
 pressure data expressed as mean  standard deviation . t2d : individuals with type 2 diabetes ; 
 nd : individuals without t2d ; bmi : body mass index ; hba1c : glycated 
 hemoglobin ; * significant difference ( p<0.05 ) all experimental sessions were carried out at the laboratory of physical evaluation and 
 training ( lafit ) of the universidade catlica de braslia 2  h after 
 volunteers eaten a standardized breakfast of a moderate glycemic index meal without any 
 substances that could have directly affected the hr and/or the bp . the participants were 
 given a physical evaluation including anthropometric measurements ( body mass , height and 
 body fat percentage ) and then performed an incremental exercise test ( it ) . during the it , 
 measurements of hr , bp and ventilatory variables were continuously monitored . to carry out 
 the measurement of body fat percentage by bipolar bioimpedance , the individuals were told 
 to : avoid caffeine and alcohol for 24 hours before the test ; not perform physical activity 
 or eat a heavy meal for at least 4 hours before the test ; and suspend diuretic medication 24 
 hours before the test36 . the it was performed on a cycle ergometer ( monark , 828 e , valburg / sweden ) at 60  rpm , and 
 began one minute at zero watt ( w ) load , followed by increments of 15  w every 3 minutes until 
 voluntary exhaustion . the cardiologist of the laboratory monitored the electrocardiogram 
 ( ecg ) of the volunteers throughout the test in order to identify any abnormality . during the period before the exercise , as well as during the last 30 seconds of each stage , 
 blood pressure ( bp ) was measured non - invasively by the auscultatory method using a mercury 
 column sphygmomanometer ( tycos instrumentos hospitalares , so paulo , brazil ) . expired gases 
 were measured during the it through a gas analyzer ( metalyzer 3b , cortex biophysik , leipzig , 
 germany ) that was previously calibrated with a 3-l syringe ( flow calibration ) and a standard 
 mixed gas containing 4.9% co2 and 17% o2 ( gas calibration ) . the values 
 of ventilation ( ve ) and oxygen uptake ( vo2 ) were recorded breath - by - breath , but , 
 they only were analyzed every 20  s in each 3-min stage . the ventilation ( ve ) kinetics during the it stages were used to identify the occurrence of 
 vt by two experienced researchers . this was considered to be the exercise intensity above 
 which an over proportional increase in ve was observed in relation to increasing 
 workload37 . systolic blood pressure ( sbp ) and hr were collected in the final minute of each stage . the 
 dpbp was considered to be the exercise intensity at which an over proportional increase in 
 dp was observed in relation to increasing workload . two experienced researchers determined 
 dpbp , and when a discrepancy between them occurred , a third researcher was consulted . all 
 the plots were blinded , therefore the researchers did not know the identity of the subjects 
 or the conditions of the test . it is noteworthy that the same evaluator , which did not 
 participated in the determination of dpbp and vt , carried out all collections of bp and hr . blinded to the 
 analysis . after assessing the normality and homogeneity of data through the shapiro - wilk and levene s 
 test , respectively , the data were presented as means (  ) standard deviation . in order to 
 compare the characteristics of the groups , the student s t - test for independent samples was 
 conducted . between and within groups comparisons when any of the dependent variables did not show sphericity in mauchly s 
 test , the epsilon of greenhouse - geisser was used to analyze the f 
 statistic . since there were only two groups , the post hoc is unable to locate the 
 differences , therefore , it was necessary to apply parallel test , named : pairwise 
 comparisons . thus , the paired student s t - test was used to compare the anaerobic threshold 
 identification methods within groups ( vt and dpbp ) . the effect size within ( vt and dpbp ) and 
 between groups ( t2d and pearson s correlation coefficients were 
 used to verify the relationships between the studied methods used to determine anaerobic 
 threshold . for the sample size calculation , the statistical power ( 1- ) was used a priori , 
 using comparison analysis applied ( anova for repeated measures ) , an effect size of 
 f=0.35 and an alpha of 5% . furthermore , the bland and altman technique 
 was used to verify the level of agreement between the different methods39 . a significance level of 5% ( p<0.05 ) all the 
 procedures were carried out using the statistical package for the social sciences ( spss 
 20.0 ) and g*power ( version 3.1.9.2 ) . the dpbp was identified in all 11 nd individuals and in 9 from 11 t2d individuals ( 81.8% ) , 
 with sbp being primarily responsible for the dpbp in almost half of all cases ( table 1 ) . the results presented in table 3table 3.workload ( watts ) , heart rate ( bpm ) and oxygen uptake 
 ( mlkgmin ) measurements at vt and dbpb of the t2d and nd 
 groupsparametert2d ( n=9)nd ( n=10)workload ( watts)dpbp45  21.260  29.2vt40  24.963  30.6heart rate(bpm)dpbp124.7  13.6119.1  17.4vt122.1  14.6121.4  19.1vo2 
 ( mlkgmin)dpbp14.6  2.415.1  2.9vt14.1  3.415.3  3.6data expressed as mean  standard deviation . t2d : individuals with type 2 diabetes ; 
 nd : individuals without t2d ; dpbp : double product breakpoint ; vt : ventilatory 
 threshold show no there were no significant differences between the workloads ( watts ) , 
 hr ( bpm ) and vo2 corresponding to the at identified by the vt and dpbp methods . further , for the t2d group , strong and significant correlations ( p<0.01 ) between 
 workloads at vt and dbpb ( r=0.853 ) , hr ( r=0.714 ) , and 
 vo2 ( r=0.863 ) were found . strong and significant correlations 
 ( p<0.001 ) were also found in the nd group for all parameters investigated ; they were 
 r=0.923 for the workload at vt and dpbp , r=0.881 for hr , 
 and r=0.863 for vo2 . t2d : individuals with type 2 diabetes ; 
 nd : individuals without t2d ; dpbp : double product breakpoint ; vt : ventilatory 
 threshold the bland and altman analyses indicate there was good agreement for the vo2 
 ( lmin ) corresponding to vt and dpbp based on the low bias and narrows limits 
 of agreement [ bias (  95% of confidence interval ) ] for vt and dpbp [ 0.03 ( 0.11 ) 
 lo2min ] for the t2d group , and vt and dpbp [ 0.02 ( 0.13 ) 
 lo2min ] for the nd group . the main finding of this research is that the dpbp can be used to estimate the at of t2d 
 and nd individuals , since there were no significant ( p<0.05 ) differences between the 
 workloads ( watts ) , hr and vo2 of the vt and dpbp methods . furthermore , the effect 
 size analyses also demonstrated that the visual differences of the variables mentioned 
 above , had little ( small ) or no effect , according to cohen s d38 . from a physiological point of view , it is presumed that the dp could be a marker of at 
 determination , to the extent that , when performing an incremental exercise test , there is a 
 gradual reduction in the vagal activity and consequent increase in sympathetic nervous 
 activity . however , at a certain intensity , a complete vagal withdrawal is expected and this 
 presents as a persistent depression of the autonomic nervous system until the end of the 
 tests , featuring the hrv threshold2 , 40 , 41 . accordingly , there is a marked increase in sympathetic nerve 
 activity , which results in a significant elevation of catecholamines , which is known as the 
 catecholamines threshold12 . the increased 
 levels of catecholamines , in turn , result in a marked increase in bp and hr , and thus on dp , 
 and as a result the dpbp15,16,17,18,19 . furthermore , 
 increased levels of catecholamines also produce a significant increase in glycolytic 
 activity42 , enabling for the 
 identification of the glycemic and lactate thresholds3 . this increased glycolysis also contributes to a sharp increase in 
 co2 production which causes hyperventilation and results in the appearance of 
 the vt43 . consequently , it is reasonable to infer that , similar to other markers ( hrv , 
 catecholamines , glucose , lactate and ventilation ) , the dp can also be used to determine the 
 at , with the advantage of it being a non - invasive and low cost method . exercise tests 
 involving blood collection and biochemical measures , and the use of expensive apparatus for 
 expired gases analysis , as well as trained professionals who know protocols are high - priced , 
 and thus inaccessible to a major portion of the t2d population . interestingly , although there was no significant difference of the workloads ( watts ) 
 between the groups ( t2d and nd ) , the effect size of the difference was considered medium 
 ( d=0.588 ) for dpbp and large ( d=0.824 ) for vt . from a 
 practical point of view , it is noteworthy that the effect size is considered the main 
 finding of a quantitative study , with the statistical significance ( p ) being the least 
 important44 , 45 , since the relevant point is the magnitude of differences45 . with regard to the internal load variables ( hr and vo2 ) , these did not present 
 significant differences ( p>0.05 ) between the groups ( t2d and nd ) , while the effect sizes 
 of the differences were small or even null . additionally , intra - group differences were 
 always null . moreover , the fact that significant differences ( p>0.05 ) were not observed 
 between the internal load variables ( hr and vo2 ) of t2d and nd groups , may be 
 partly explained by the higher cardiorespiratory capacity of the healthy individuals , as 
 they reached an absolute external load ( watts ) , but with a similar cardiorespiratory 
 responses ( hr and vo2 ) . additionally , another aspect that should be considered 
 regarding the absence of significant differences between the t2d and nd groups , is that they 
 presented quite similar characteristics ( table 
 2 ) , since the only variable that was different between the groups was glycated 
 hemoglobin ( hba1c ) . it is noteworthy that the statistics reveal there were strong and significant correlations 
 between workloads ( watts ) , hr and vo2 , and also a good agreement in both the t2d 
 and nd groups . , who reported a strong 
 and significant correlation between vo2 at the lactate threshold ( lt ) and dpbp 
 ( r=0.86 ; p<0.01)16 . likewise tanaka et al . also observed a strong and significant correlation between the dpbp 
 and the lt ( r=0.90 ; p<0.01 ) in a sample of 90 patients17 . additionally , kumagai et al . identified 
 the dpbp in 63 t2d individuals in a submaximal ramp test ( rating of perceived exertion of 
 15 ) performed on a cycle ergometer23 . however , it is noteworthy that in that study the dpbp was not compared with any other at 
 identification method . regarding the comparison of dpbp and vt , brubaker et al . previously demonstrated a strong 
 and significant correlation between the methods ( r=0.81 , p<0.01 ) in a 
 progressive test on a treadmill , and suggested that dpbp could be a valid alternative to vt 
 for individuals with coronary artery disease15 . also omiya et al . reported a high and significant association 
 between workloads ( watts ) ( r=0.95 ; p=0.01 ) of both the dpbp and vt of 15 
 patients with cardiovascular diseases18 . similarly , hargens et al . conducted an elegant longitudinal study in order to evaluate the 
 effect of eight weeks of aerobic training at vigorous intensity on dpbp and vt . they 
 evaluated 7 men and 11 sedentary women , using a ramp protocol on a cycle ergometer , and 
 observed that hr and vo2 at baseline and at the end of the training period were 
 similar ( p>0.05 ) and showed good agreement19 . the fact that this previous study reported an increase of dpbp 
 after training , confirms it is a reliable and sensitive method of identifing at adaptations 
 to training . one limitation of the present study was that the intensity of the maximum lactate steady 
 state ( mlss ) was not determined for comparison with the investigated protocols of dpbp and 
 vt . the determination of mlss is considered the gold standard among the exercise assessment 
 methods1 . van schuylenbergh indicate that this parameter is not different from the lactate 
 threshold and vt46,47,48 . thus , it is reasonable 
 to infer that the methods investigated in this study , dpbp and vt , which did not differ 
 between themselves , may also represent the mlss intensity . the present study demonstrated that the dpbp can be easily determined during incremental 
 exercise in both t2d and nd controls . additionally , the dpbp happened at exercise 
 intensities related to the vt in both the populations studied , suggesting that dpbp can be a 
 useful marker of exercise intensity associated with at .