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      Inter-Individual Responses of Maximal Oxygen Uptake to Exercise Training: A Critical Review

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      Sports Medicine
      Springer Nature

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          Abstract

          It has recently been reported how to quantify inter-individual differences in the response to an exercise intervention using the standard deviation of the change scores, as well as how to appraise these differences for clinical relevance. In a parallel-group randomised controlled trial, the key trigger for further investigation into inter-individual responses is when the standard deviation of change in the intervention sample is substantially larger than the same standard deviation derived from a suitable comparator sample. 'True' and clinically relevant inter-individual differences in response can then be plausibly expected, and potential moderators and mediators of the inter-individual differences can be explored. We now aim to critically review the research on the inter-individual differences in response to exercise training, focusing on maximal oxygen uptake (VO2max). A literature search through the relevant bibliographic databases resulted in the identification of six relevant studies that were published prior to the influential HEalth, RIsk factors, exercise Training And GEnetics (HERITAGE) Family Study. Only one of these studies was found to include a comparator arm. Re-analysis of the data from this study, accounting for random within-subjects variation, revealed an absence of clinically important inter-individual differences in the response of VO2max to exercise training. The standard deviation of change was, in fact, larger (±5.6 mL/kg/min) for the comparator than the intervention group (±3.7 mL/kg/min). We located over 180 publications that resulted from the HERITAGE Family Study, but we could not find a comparator arm in any of these studies. Some authors did not explain this absence, while others reasoned that only inter-individual differences in exercise response were of interest, thus the intervention sample was investigated solely. We also found this absence of a comparator sample in on-going studies. A perceived high test-retest reliability is offered as a justification for the absence of a comparator arm, but the test-retest reliability analysis for the HERITAGE Family Study was over a much shorter term than the length of the actual training period between baseline and follow-up measurements of VO2max. We also scrutinised the studies in which twins have been investigated, resulting in concerns about how genetic influences on the magnitude of general within-subjects variability has been partitioned out (again in the absence of a comparator no-training group), as well as with the intra-class correlation coefficient approach to data analysis. Twin pairs were found to be sometimes heterogeneous for the obviously influential factors of sex, age and fitness, thereby inflating an unadjusted coefficient. We conclude that most studies on inter-individual differences in VO2max response to exercise training have no comparator sample. Therefore, true inter-individual differences in response cannot be quantified, let alone appraised for clinical relevance. For those studies with a comparator sample, we found that the inter-individual differences in training response were not larger than random within-subjects variation in VO2max over the same time period as the training intervention.

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          Most cited references45

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          Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial.

          Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination. To examine the benefits of aerobic training alone, resistance training alone, and a combination of both on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes. A randomized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise program between April 2007 and August 2009. Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of anthropometry and fitness. The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c) were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1 kg; P < .05) compared with the control group. Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone. clinicaltrials.gov Identifier: NCT00458133.
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            High responders and low responders: factors associated with individual variation in response to standardized training.

            The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating an equivalent homeostatic stress between individuals than other methods. Individual variation in the homeostatic stress associated with each training session would result in individuals experiencing a different exercise 'stimulus' and contribute to individual variation in the adaptive responses incurred over the course of the training program. Furthermore, recovery between the sessions of a standardized training program may vary amongst individuals due to factors such as training status, sleep, psychological stress, and habitual physical activity. If there is an imbalance between overall stress and recovery, some individuals may develop fatigue and even maladaptation, contributing to variation in pre-post training responses. There is some evidence that training response can be modulated by the timing and composition of dietary intake, and hence nutritional factors could also potentially contribute to individual variation in training responses. Finally, a certain amount of individual variation in responses may also be attributed to measurement error, a factor that should be accounted for wherever possible in future studies. In conclusion, there are several factors that could contribute to individual variation in response to standardized training. However, more studies are required to help clarify and quantify the role of these factors. Future studies addressing such topics may aid in the early prediction of high or low training responses and provide further insight into the mechanisms of training adaptation.
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              Genomic predictors of the maximal O₂ uptake response to standardized exercise training programs.

              Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O(2) uptake (VO(2max)) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genome-wide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in VO(2max) Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 × 10(-4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in VO(2max) trainability. Subjects who carried ≤9 favorable alleles at these 21 SNPs improved their VO(2max) by 221 ml/min, whereas those who carried ≥19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ~6% of the training response of VO(2max). The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K(+) channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 ~68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains in VO(2max) in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response of Vo(2max) to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted.
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                Author and article information

                Journal
                Sports Medicine
                Sports Med
                Springer Nature
                0112-1642
                1179-2035
                August 2017
                January 17 2017
                : 47
                : 8
                : 1501-1513
                Article
                10.1007/s40279-017-0680-8
                28097487
                ece0b04a-b83e-4a6a-862a-ff65f7bae042
                © 2017

                http://www.springer.com/tdm

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