The current standard measure of cardiorespiratory fitness introduces confounding by body mass: the DR's EXTRA study

Abstract

OBJECTIVE: Cardiorespiratory fitness is currently estimated by dividing maximal oxygen consumption (VO 2max ) by body weight (per-weight standard). However, the statistically correct way to neutralize the effect of weight on VO 2max in a given population is adjustment for body weight by regression techniques (adjusted standard). Our objective is to quantify the bias introduced by the per-weight standard in a population distributed across different categories of body mass. DESIGN: This is a cross-sectional study. SUBJECTS AND METHODS: Baseline measures from participants of the Dose-Responses to Exercise Training Study (DR's EXTRA), 635 men (body mass index (BMI): 19--47 kg m À2 ) and 638 women (BMI: 16--49 kg m À2 ) aged 57--78 years who performed oral glucose tolerance tests and maximal exercise stress tests with direct measurement of VO 2max . We compare the increase in VO 2max implied by the per-weight standard with the real increase of VO 2max per kg body weight. A linear logistic regression model estimates odds for abnormal glucose metabolism (either impaired fasting glycemia or impaired glucose tolerance or Type 2 diabetes) of the least-fit versus most-fit quartile according to both per-weight standard and adjusted standard. RESULTS: The per-weight standard implies an increase of VO 2max with 20.9 ml min À1 in women and 26.4 ml min À1 in men per additional kg body weight. The true increase per kg is only 7.0 ml min À1 (95% confidence interval: 5.3--8.8) and 8.0 ml min À1 (95% confidence interval: 5.3--10.7), respectively. Risk for abnormal glucose metabolism in the least-fit quartile of the population is overestimated by 52% if the per-weight standard is used. CONCLUSIONS: In comparisons across different categories of body mass, the per-weight standard systematically underestimates cardiorespiratory fitness in obese subjects. Use of the per-weight standard markedly inflates associations between poor fitness and co-morbidities of obesity.

VO 2max /kg is expected to be lower in obese individuals!

“…Therefore, dividing VO 2max uptake by total body weight (i.e., lean mass + fat mass) systematically underestimates cardiorespiratory fitness in obese individuals. Our research group has demonstrated both, the introduction of a substantial body-composition bias if VO 2max is divided by total body weight [3] and the elimination of body-composition bias if VO 2max is divided by lean mass [4]. These results agree with the previous finding of others that VO 2max follows a linear function of lean mass [5].…”

Dietary associations with prediabetic states—The DR's EXTRA Study (ISRCTN45977199)

“…This is all the more remarkable, as we have shown recently that in the same population that VO 2max expressed as ml oxygen uptake per minute and kg body weight systematically underestimates cardiorespiratory fitness in obese subjects. 32 As obesity is both, a major risk factor for T2D and a link in the chain of causation between diet and T2D, one would have expected a weakening of all diet-prediabetic state associations upon adjustment for VO 2max .…”

The relationship between insulin sensitivity and maximal oxygen uptake is confounded by method of adjustment for body composition

“…Use of the weight ratio method to standardize for body size overestimates the VO 2 max for lighter individuals and underestimates it for heavier individuals. 6,7,[9][10][11] As a result, the division creates a spurious association with other variables, such as insulin sensitivity, as illustrated in a study of overweight Hispanic youth. 12 The primary aim of our analysis is to demonstrate the differences that arise when ratios, rather than partial correlation coefficients, are used to standardize VO 2 max in determining its correlation with insulin sensitivity.…”

“…dividing VO 2 max by weight, or VO 2 max/WT) is common both in research and in clinical practice. [5][6][7][8][9][10][11] The purpose of such division is presumably to create a new variable that is independent of weight. Division by weight, however, generally fails to accomplish this.…”