PHYSICAL ACTIVITY (D WARBURTON, SECTION EDITOR)

The Secondary Prevention of Cardiometabolic Diseasein Diabetes Patients: Novel Advancements and the Way Forward

Leanna Lee & Paul Oh

Published online: 12 July 2014# Springer Science+Business Media New York 2014

Abstract The prevalence of type 2 diabetes mellitus (T2DM)in developed countries around the world has never beforereached greater proportions. Given the chronic nature of thedisease and its frequent, concomitant presence of cardiomet-abolic risk factors, patients with T2DM are most likely toexperience fatalities associated with cardiovascular disease(CVD). Chronic cardiometabolic disease and T2DM are pre-ventable, reversible, and can be delayed with the appropriatelifestyle choices or modifications. Recent findings examiningintensive lifestyle interventions targeting weight loss, and thepotential feasibility of incorporating high intensity intervaltraining (HIIT) into the exercise regimens of patients withT2DM, encourage optimism as we, as a society, move intothe future and seek a novel approach to extricate ourselvesfrom this trend of premature death associated with chroniccardiometabolic disease. The way forward in the secondaryprevention of cardiometabolic disease involves elicitingchange in our perception of physical activity at the earlieststage in life possible: childhood.

Keywords Type 2 diabetes . Cardiometabolic disease .

Primary prevention . Secondary prevention . Exercise . Highintensity interval training (HIIT) . Continuousmoderateintensity training (CMIT) . Vigorous physical activity (VPA) .

Moderate-vigorous physical activity (MVPA) . Physicalactivity . Overweight . Obese . Bariatric surgery .

Cardiorespiratory fitness (CRF) . Children . Adolescence .

Cardioprotective

Introduction

It is undeniable that we have entered into an era in which weare faced with an alarming epidemic of type 2 diabetesmellitus (T2DM) [1, 2]. With nearly a sixfold global increasein the number of individuals afflicted with diabetes from theyear 1985 to 2000 [1], and predictions from the World HealthOrganization that there will be an additional 39 % increase indiabetes cases around the world from the year 2000 to 2030[1], it behooves us to no longer turn a blind eye to this globalepidemic and to take decisive action moving forward into thefuture. This is of utmost importance in light of statistical datasuggesting that T2DM now ranks as the sixth-leading cause ofmortality in developed countries [3], with almost 70 % ofthose deaths being linked to cardiovascular disease (CVD)[4]. Unfortunately, it is commonplace that the majority ofindividuals with T2DM also present with accompanying car-diometabolic risk factors which include being overweight orobese, increased abdominal adiposity, dyslipidemia, hyperten-sion and impaired glucose tolerance, which further predis-poses them to CVD-related mortality [5]. Moreover, it isdifficult to condone the ever increasing economic health bur-den of T2DM in our society [6, 7], when it has been well-established that lifestyle factors and/or modifications provideus with the necessary weapons to combat the majority ofchronic cardiometabolic diseases [8, 9]. This review en-deavors to highlight the most recent, novel, and relevantfindings with respect to exercise-related lifestyle interventionsin the secondary prevention of cardiometabolic disease indiabetes patients, and to provide suggestions for the futureand the way forward.

This article is part of the Topical Collection on Physical Activity

L. Lee (*) : P. OhUniversity Health Network Cardiovascular Prevention andRehabilitation Program, Toronto Rehabilitation Institute (UHN-TRI),347 Rumsey Road, Toronto, ON, Canada M4G 1R7e-mail: leanna.lee@uhn.ca

P. Ohe-mail: Paul.Oh@uhn.ca

Curr Cardiovasc Risk Rep (2014) 8:396DOI 10.1007/s12170-014-0396-3

The Effect of Weight Loss in T2DM

The Look AHEAD Research Group conducted a large-scale(n=5145), randomized, clinical trial across 16 study sites in theUnited States, in order to determine whether an intensivelifestyle intervention targeting weight loss through dietary re-striction and increased physical activity in overweight andobese individuals with T2DM would decrease the risk ofcardiovascular morbidity and mortality, over a 13.5 year followup period [10••]. The results of the study were cast in a negativelight, based on a futility analysis performed roughly 10 yearsinto the study, which revealed that there were no significantdifferences between the intensive lifestyle intervention andcontrol groups, with respect to the composite primary outcomeof first occurrence of death from cardiovascular causes, nonfa-tal myocardial infarction, nonfatal stroke, or hospitalization forangina [10••]. Furthermore, there was only an approximated1 % chance of demonstrating a significant, positive result at theend of the intended 13.5 year follow up period [10••].

The goal of the intensive lifestyle intervention was to reducebody weight by a minimum of 7 % and to maintain that weightloss primarily through caloric restriction of 1200-1800 kcal perday, with less than 30 % of those calories coming from fat, andgreater than 15% of those calories coming from protein sources[10••]. Moreover, the caloric restriction was to becomplemented by a minimum, weekly physical activity regi-men, involving 175 minutes of moderate intensity exercise[10••]. The control group received standard diabetes educationand support three times per year from year 1-4 in the study, andthen just once per year after year 4 [10••]. Although the studywas terminated early, and did not demonstrate a reduction incardiovascular morbidity and mortality after a median follow-up of 10 years [10••], there were many encouraging and posi-tive outcomes in relation to the secondary prevention of car-diometabolic disease that the authors would like to emphasize,and hope to draw upon for future directions.

One year into the study, the lifestyle intervention groupachieved a meanweight loss of 8.7%, which was significantlygreater than a weight loss of 0.7 % in the control group (p<0.001) [10••]. Similarly, upon one year follow up of the study,the lifestyle intervention group significantly improved physi-cal fitness (as demonstrated by greater METS achieved duringmaximal exercise testing) (p<0.001), reduced waist circum-ference (p<0.001), decreased levels of glycated hemoglobin(p<0.001), systolic and diastolic blood pressure (p<0.05 forboth), and triglycerides (p<0.05), and increased levels ofHDL cholesterol (p<0.05), compared to the control group[10••]. These clinically meaningful improvements in cardio-metabolic risk factors after one year of lifestyle interventioncould be partially responsible for the attenuation/reversal ofdiabetes, over the first four years of the study reported in thisgroup [10••]. Furthermore, the intervention group patientsdemonstrated less reliance on insulin treatment and the use

of statins over the initial four years of the study, compared tothe control group [10••]. These results should be viewed withoptimism, as this corroborates much of the literature advocat-ing exercise and intensive lifestyle interventions (with weightloss being one of their targets) playing a quintessential role inpreventing and/or delaying the onset of T2DM [11, 12].

The conspicuous and pertinent finding from this study thatcommands attention is that this initial 8.7 % reduction in meanbody weight in the intervention group was not sustainedbeyond the first year of study follow-up [10••]. Similarly, allof the improvements in cardiometabolic risk factors that wereapparent after one year of study follow-up in the interventiongroup diminished in parallel with the regain in weight [10••].Therefore, with ameager 2.5% difference inmeanweight lossbetween the intervention group and the control group (6.0 %versus 3.5 %, respectively) at the 10 year median follow-upand termination of the study [10••], it is certainly not surpris-ing that the study yielded a negative result and failed todemonstrate any differences in cardiovascular morbidity andmortality rates between the two groups.

These findings strongly suggest that a weight loss of at least~9 % in T2DM patients with BMI values greater than 30 kg/m2

is effective in the secondary prevention of cardiometabolicdisease risk factors, but that this minimum weight loss percent-age must be chronically sustained in order to elicit these life-long improvements in or reversal of cardiometabolic disease.The authors postulate that a weight loss target of 7-10 % inT2DM patients who have BMI values >30 kg/m2 should beincreased to a target weight loss of 17-20 %, a significantlymore aggressive target recently observed in T2DM patientsundergoing bariatric surgery [13, 14••]. The Swedish ObeseSubjects study demonstrated a reduction in cardiovascularmorbidity and mortality rates, along with increased rates ofdiabetes remission, in T2DM patients after a 10 year follow-up, in which patients sustained a weight loss of 17 %, after aninitial weight loss of ≥20 % achieved by bariatric surgery[14••]. These findings encourage and warrant future, large-scale, randomized, clinical trials (RCTs) that include an inten-sive lifestyle intervention in patients with T2DM, involvingdietary/caloric restriction in conjunction with an exercise regi-men targeting a weight loss of 20 %, and its effects on cardio-vascular morbidity and mortality. Furthermore, future direc-tions should also include studies comparing equivalent 20 %weight loss achieved through either intensive lifestyle interven-tion or through bariatric surgery in patients with T2DM, inorder to determine if significant differences exist between thegroups with respect to cardiovascular related events.

The Effect of Exercise Intensity in T2DM

Current physical activity guidelines, including those offeredby the Canadian Diabetes Association and American Diabetes

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Association, recommend a minimum of 150 minutes of mod-erate to vigorous aerobic exercise per week in the preventionand treatment of chronic cardiometabolic diseases [15]. De-spite the overwhelming body of evidence shown in bothobservational and RCTs that chronic, regular physical activityplays a quintessential role in both the primary and secondaryprevention of type 2 diabetes [11, 12, 16, 17] it is failing toresonate among our society today. We find ourselves strug-gling to implement changes in attitude and sustained behaviorthat are conducive to climbing our way out of an unsettlingfuture, riddled with type 2 diabetes and other chronic diseasesthat result in premature death. There remains much hope andoptimism however, as we examine some more recent findingsthat suggest the potential feasibility and efficacy of highintensity interval training (HIIT) in patients with T2DM, andits role in the secondary prevention of cardiometabolic disease[18•, 19, 20••, 21].

There has been much interest in investigating HIIT com-pared to the more common exercise modality of continuous,moderate intensity exercise training (CMIT) in both young[22], and middle-aged, healthy individuals [23], and in indi-viduals with cardiometabolic disorders [24, 25], in order todetermine whether there are greater fitness gains andcardioprotective benefits conferred through HIIT versusCMIT. These limited studies, with very small sample sizes,have suggested that HIIT significantly improves cardiorespi-ratory fitness (CRF), as measured by VO2peak, compared toCMIT in patients with cardiometabolic disease [24, 25]. Al-though we must exercise caution in interpreting results fromthese small-scale studies, this finding is of paramount impor-tance, as CRF is a modifiable risk factor for cardiometabolicdisease and is cardioprotective, even in the presence of car-diovascular disease and/or its risk factors [26]. Moreover, ithas been established that there is a 10-25 % increase in thelikelihood of survival with an increase in VO2peak of onemetabolic equivalent (1-MET), or 3.5 mL/kg/min [27]. There-fore, it is extremely encouraging that Terada et al. [18•] wereable to show the feasibility and preliminary efficacy of HIIT inpatients with T2DM for the first time, in a RCT.

Patients with T2DM were randomized into either HIIT orCMIT groups, and exercised under supervised conditions fivedays per week for 12 weeks [18•]. Along with feasibility,adherence, retention, feeling states and self-efficacy, second-ary outcome measures of body composition and HbA1C wereexamined pre and post-12 week exercise intervention to eval-uate the efficacy of the pilot study [18•]. Patients in the MICTgroup performed alternate days of treadmill walking or sta-tionary cycling at a work load eliciting an intensity of 40 % ofoxygen consumption reserve (VO2R), the ratio of net oxygencosts to net maximal oxygen consumption [28]. Exerciseduration was increased from 30 minutes for weeks 1-4 of thestudy, to 45 minutes from weeks 5-8, and to 60 minutes fromweeks 9-12, for both MICT and HIIT groups [18•]. The HIIT

group performed one-minute intervals of treadmill walking orstationary cycling on alternate days at 100 % VO2R, followedby a 3-minute recovery at 20 % VO2R. Any remaining timeleft in the session was spent exercising at 40 % VO2R, toensure that an average workload of 40%VO2Rwas performedin both study groups [18•]. On Wednesdays of each week ofthe study, patients in the HIIT group also performed the CMITprotocol. The important findings from this pilot study werethat a 97 % adherence rate was achieved in both HIIT andCMIT groups, and that there was no attrition, which may beattributed to patients experiencing equally positive feelingstates, low psychological distress stemming from the exercisetasks, and high self-efficacy and the sense of achievement andsatisfaction from performing the exercise intervention [18•].While this study provides evidence for the feasibility of in-corporating HIIT into the exercise regimens of patients withT2DM, the small sample size of n=15, and the baselinesignificantly lower saggital diameter and waist circumferencein the HIIT versus CMIT group [18•] precludes us fromaccepting that the study had sufficient power to detect truedifferences in the secondary outcome measures of body com-position. Nevertheless, with this cautionary note in mind, asignificant reduction in trunk fat was observed in the HIITgroup only, while the total percentage of body fat, percentageof leg fat, and subcutaneous fat width were reduced in bothgroups [18•]. Furthermore, there were no differences observedin fasting blood glucose, HbA1C, blood lipid profile, bodyweight, saggital diameter, waist circumference and percentageof arm fat from baseline to post-exercise intervention in eithergroup [18•]. Analysis of Covariance (ANCOVA) similarlyfailed to demonstrate differences between the two exerciseinterventions. While this preliminary study by Terada et al.[18•] showed that HIIT and CMIT reduced total percentage ofbody fat to the same extent, and did not elicit any changes inHbA1C in this relatively, well-controlled sample of T2DMpatients, the recent work from Karstoft et al. [20••] demon-strated significant improvements in CRF, body composition,and glycemic control in patients with T2DM who performedHIIT compared to CMIT after a four month intervention.

A cautionary note must be issued again as we examine therecent findings from a small-scale study performed byKarstoft et al. [20••], in which T2DM patients were random-ized to a CMITwalking group (n=12), a HIITwalking group(n=12), and a control group (n=8).The CMIT group walkedat a workload that elicited a target energy expenditure rate of≥55 % of peak energy expenditure, which was obtained fromthe initial peak VO2 graded walking test, while the HIITgroup walked at alternating workloads that elicited a targetenergy expenditure of ≥70 % of peak energy expenditure forthree minutes, followed by three minutes of slow walking,described as being below the 70 % of peak level [20••].Patients performed five, 60 minute exercise sessions eachweek for four months, and heart rate and accelerometry data

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were uploaded and monitored biweekly to gauge trainingintensity and effort [20••].

In agreement with the findings from Terada et al. [18•],energy expenditure between the MICT and HIIT walkinggroups was comparable (p>0.05), and adherence rates werehigh ( mean of 89±4 % of training volume performed com-pared to prescribed) [20••]. Contrary to Terada et al.’s [18•]findings, however, was that VO2peak was shown to improveby a mean of 16.1±3.7 % in the HIIT walking group com-pared to the CMITwalking group (p<0.001) [20••]. Given ourprevious discussion of CRF in the primary and secondaryprevention of cardiometabolic disease and risk factors, thisfinding is of particular importance and provides further pre-liminary evidence for the feasibility and the potential efficacyof incorporating HIIT into the physical activity regimens ofT2DM patients moving into the future. Glycemic controlworsened from baseline to 4 months in the control group,remained unchanged in the CMIT walking group, and im-proved (as demonstrated by decreased mean and maximumlevels of continuous glucose monitoring [CGM], p<0.05) inthe HIITwalking group [20••]. Compared to the CMITwalk-ing group, the HIIT walking group achieved a loss of 4.3±1.2 kg of body weight (p<0.001), body fat mass decreased by3.1±0.7 kg (p<0.001), abdominal visceral fat declined by0.54±0.15 L (p<0.001), and these factors likely contributedto the improvement in waist-to-hip ratio as well (p<0.01)[20••]. Both the control and CMIT walking groups failed toshow any changes in body composition parameters frombaseline to 4 months, and there were no significant changesin HbA1c or fasting glucose among any of the three groups[20••]. Despite the small sample size and resultant limitedgeneralizability to the greater population of T2DM patients,HIIT demonstrated superior improvements in CRF, bodycomposition, and glycemic control compared to CMIT in thisstudy [20••], which are all secondary cardiometabolic riskfactors that are prevalent in patients with T2DM. Therefore,the authors conjecture that HIIT shows great promise as afeasible and effective strategy in the secondary prevention ofcardiometabolic disease in this population as we move for-ward into the future.

The Way Forward: Cardiometabolic Disease PreventionMust Commence in Adolescence

Although we are encouraged by the recent, small-scale, pre-liminary studies demonstrating the feasibility and efficacy ofHIITexercise in T2DM, and the very high adherence rates, wemust recognize that these were short term interventions, notextending beyond four months and not necessarily generaliz-able to the greater diabetes population as a whole [18•, 19,20••]. Perhaps the most salient message gleaned from thelarge-scale, RCT examining intensive lifestyle intervention

in overweight and obese patients with T2DM that washighlighted earlier in this review [10••], was the lack ofsustainability of the significant improvement in weight loss,and cardiometabolic risk factors including CRF, waist circum-ference, glycated hemoglobin, and blood pressure beyondyear one of the study [10••]; and because there is such over-whelming evidence in support of T2DM and other chroniccardiometabolic diseases sharing common, preventable riskfactors that can be successfully precluded altogether, reversed,delayed, and/or managed by making appropriate lifestylechoices or changes [8], the quintessential issues that need tobe addressed in order to achieve the sustainability of theselifestyle interventions stem from behavioral modification, at-titudinal changes toward exercise, and intrinsic motivation.The authors are well aware that this will not be a simple taskmoving forward, but if we want to be successful in combatingcardiometabolic disease in diabetes and non-diabetes patientsalike, we need to engage this population to want to helpthemselves in living longer and higher quality lives. Theauthors believe that it is necessary to change the entire waythat society as a whole perceives vigorous physical activityand duration of physical activity in our daily lives, and theimportance of CRF in leading a healthy lifestyle, unbridled bycardiometabolic disease. In order to most effectively elicitthese societal changes in attitudes and perceptions, we suggestthat a “from the bottom-up” as opposed to a “from the top-down” approach be used. We postulate that leading a healthylifestyle with the key emphasis on high levels of physicalactivity, incorporating moderate doses of high intensity orvigorous physical activity must be introduced and ingrainedin young children and adolescents, if we are to eventuallyeliminate this notion of a “lifestyle intervention” in the sec-ondary prevention of cardiometabolic disease, and just acceptit is as our lifestyle. It should not and cannot be perceived asonerous or burdensome. It simply is a way of life. In thismanner, the secondary prevention of cardiometabolic diseaseis both entrenched and inextricably linked to the primaryprevention of cardiometabolic disease. We highlight somerecent and novel findings in the pediatric, exercise literature,in order to support our postulations and opinions as to why webelieve that this is the way forward in the secondary preven-tion of cardiometabolic disease in diabetes patients.

T2DM is more often than not the corollary of the clusteringof cardiometabolic risk factors [29], and evidence suggeststhat this not only occurs during adolescence [30], but that thisclustering of risk carries over into adulthood [31]. Further-more, higher levels of CRF in children have been shown to beassociatedwith lower cardiovascular risk profiles in adulthood[32], and that higher levels of CRF during childhood tend topersist into adulthood, thus conferring a cardioprotective ef-fect [33]. Bailey et al. [34•] recently examined clusteredcardiometabolic risk in children between the ages of 10-14years (n=100) and any associations that might exist, as

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stratified by objectively determined CRF and time spentperforming various intensities of physical activity (PA). Theclustered cardiometabolic risk score was calculated by stan-dardizing and summing the z-score values of waist circumfer-ence, total cholesterol/high-density lipoprotein ratio, triglyc-erides, blood pressure, and fasting blood glucose [34•]. Timespent in light PA (LPA), moderate-vigorous PA (MVPA), andvigorous PA (VPA) was captured using accelerometers, andreported as the average time per day during the 3 day moni-toring session [34•]. The study findings revealed that CRFwas negatively associated with waist circumference, triglyc-erides, diastolic blood pressure, and clustered cardiometabolicrisk score [34•]. VPA was found to be negatively associatedwith diastolic blood pressure, while LPAwas positively asso-ciated with waist circumference [34•]. VPAwas also shown tobe negatively associated with percentage of body fat, andconversely, LPA was shown to be positively associated withpercentage of body fat [34•]. CRF displayed a negative asso-ciation with LPA, but positive associations with both MVPAand VPA [34•]. Importantly, when the study participants werestratified as “fit” and “unfit”, according to cycle ergometryVO2max threshold values determined by Ruiz et al. [35],where “fit” boys were classified as having a CRF>42.1 mL/kg/min and “fit” girls as having a CRF>37.0 mL/kg/min, and“unfit” boys and girls were classified as achieving CRF levels<42.1 mL/kg/min and <37.0 mL/kg/min, respectively, fit par-ticipants had significantly lower clustered risk scores com-pared to unfit participants (p<0.001) [34•]. In this particularstudy, objectively measured PAwas not found to be associatedwith clustered cardiometabolic risk, however the strongestcorrelation found between CRF and PA was among CRFand VPA (r=0.39) [34•]. Contrary to these findings by Baileyet al. [34•], others have very recently observed in a 2 yearlongitudinal study of youths, between the ages of 9-15 years,that time spent in VPA at baseline was the primary predictor ofhaving lower cardiometabolic disease risk profiles, two yearslater [36•]. Another interesting observation stemming fromthis study was that despite a much greater amount of timespent in MVPA, this did not appear to carry similar beneficialcardiometabolic health implications in this population, pro-viding further evidence that even short bursts of time spentperforming VPA, similar to HIIT, could potentially be moreeffective in the prevention of cardiometabolic disease thangreater periods of time spent performing MVPA [36•]. Takentogether, these studies reiterate and build on previous findingsthat CRF during childhood and adolescence is linked to car-diometabolic risk profile into adulthood [32, 35], and thatspending more time performing VPA plays a large role inincreasing CRF, which has been shown to be cardioprotectivein both the presence and absence of cardiovascular disease[26] and in increasing the likelihood of survival [27]. This alsoprovides further support to the superior benefits that HIITmayhave in increasing CRF and, therefore, in conferring greater

benefit against cardiovascular risk and/or disease [24]. More-over, these data support the authors’ viewpoint in suggestingthat interventions targeting greater time spent performingVPA and/or HIIT and in improving CRF should begin inchildhood and adolescence [35], and that standards and guide-lines in PA and healthy, active living that are provided forschool-aged children should be revisited and revised to reflectthe necessary lifestyle modifications that will keep cardiomet-abolic disease at bay, even into adulthood.

Countries including Canada and the US, along withgoverning bodies, have adopted PA guidelines for childrenand adolescents that call for engaging in a minimum of 60 mi-nutes of MVPA per day [37–39], with the inclusion of VPA ata minimum of three times per week [37–39]. With a minimumrecommendation of 420 minutes of MVPA per week, with thefurther incorporation of a minimum of three days per weekperforming VPA, for children and adolescents [37–39], itcertainly would appear less daunting as one transitions intoadulthood and is recommended to engage in perhaps, a min-imum of 300 minutes of MVPA/week, including a minimumof three days per week engaging in VPA. If a child is alreadyaccustomed or conditioned to leading such a lifestyle, then itshould not present as a challenge for this type of lifestyle topersist into adulthood, because it is ingrained and just comesnaturally. This is how the authors perceive the “from thebottom up” strategy eventually eliciting change in society’sbattle against chronic cardiometabolic disease. The recom-mendation of 300 minutes of MVPA/week, with a minimumof three days/week engaging in VPA for adults, is similar towhat Terada et al. and Karstoft et al. [18•, 19, 20••] had theirT2DM patients progress to by the end of their study interven-tions, which demonstrated the preliminary feasibility and ef-ficacy of this type of HIITexercise regimen in this population.Thus, if the current guidelines for PA in children and adoles-cents are adopted by countries and organizations around theworld and actively implemented [37–39], then the authorsbelieve the next step is to revisit the current PA guidelinesfor adults living with and without cardiometabolic disease thatshould incorporate new target PA durations/day, as well as theinclusion of VPA or HIIT guidelines that can be followed. Atthe present time, the authors are unaware of any HIIT guide-lines existing in the diabetes population targeting the second-ary prevention of cardiometabolic disease, and believe that thetime has come for these guidelines to be established andimplemented uniformly around the world.

Conclusions

The recent epidemic of T2DM is a very real phenomenon thatposes a serious threat to us as a society, and its accompanyingcardiometabolic risk factors are together waging war withrespect to morbidity and mortality associated with CVD.

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Intensive lifestyle interventions targeting clinically significantweight loss (7-10 %) in overweight or obese patients withT2DM appear to be futile in decreasing cardiovascular mor-bidity and mortality after 10 years of follow-up, if this weightloss is not sustained over time. The recent success found inperforming bariatric surgery in this patient population, wherea weight loss of ≥20 % of body weight was achieved andsustained after a 10 year follow-up period, demonstratingreductions in cardiovascular-related events and deaths, pro-vides the impetus for attempting to achieve similar weight lossthrough lifestyle intervention, and to compare the secondaryprevention of cardiometabolic disease and the related cardio-vascular mortality rates in future studies.

Strategies to successfully implement intensive lifestyle in-terventions that have the potential to achieve weight loss of≥20 % of body weight find strength from novel findingsdemonstrating the preliminary feasibility and efficacy of en-gaging in HIIT and in increasing weekly MVPA to 300 mi-nutes in patients with T2DM. The preliminary findings show-ing the superior benefits of HIIT over MICT/MVPA in im-proving CRF in this patient population is also encouraging,given the cardioprotective effects of higher CRF levels and itspredictive capacity for survival.

As we move into the future and consider the way forward,the authors postulate that the secondary prevention of cardio-metabolic disease in diabetes patients is inextricably linked tothe primary prevention of cardiometabolic disease, and thatprimary prevention requires a complete overhaul of the wayour society perceives the duration of PA in our daily lives, theengagement in VPA or HIIT, and the role that CRF all syner-gistically play in leading lives free of chronic cardiometabolicdisease. Given the mounting evidence showing 1) that theclustering of cardiometabolic risk factors can occur in child-hood and then eventually persists into adulthood, 2) that CRFis of utmost importance and its cardioprotective role ispervasive as early as childhood and in adolescence, and 3)that time spent engaged in VPA as a youth is associatedwith lower cardiometabolic risk profile two years later,interventions must occur “from the bottom-up” and theymust start with our children. Universal PA activity guide-lines emphasizing daily MVPA duration and the incorpora-tion of moderate doses of VPA in childhood must be strictlyimplemented worldwide, in addition to revised, updatedand novel PA guidelines for adults living with or withoutchronic metabolic diseases, reflecting the childhood PAguidelines and the inclusion of moderate doses of VPAand how to safely perform HIIT. The authors certainlyrecognize that this is no small challenge to systemicallyimplement a new approach, mindset, and set of guidelines,in order to elicit a behavioral change that is targeting thesecondary prevention of cardiometabolic disease, but webelieve it is the way forward and we cannot be faint at heartin our approach.

Compliance with Ethics Guidelines

Conflict of Interest Leanna Lee and Paul Oh declare no conflicts ofinterest.

Human and Animal Rights and Informed Consent This article doesnot contain any studies with human or animal subjects performed by theauthor.

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