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PLoS ONE | www.plosone.org

3

p#0.05.
p,0.01.
{{{
p,0.001 indicates significant change score within a group.
To convert pmol/L of insulin to mU/L, divide by 6.945. To convert mmol/L of HDL-C to mg/dL, divide by 0.02586. To convert mmol/L of triglycerides to mg/dl, divide by 0.01129.
doi:10.1371/journal.pone.0037887.t003
{{

{

131.7615.6

23.7610.9{{

133 + 16

1 + 13

N/A

N/A
24.3613.8{
23.1611.8

131.3620.4
138.5612.7{

0.266.2

21.6615.1

138.9613.4

1612.7

122.8612.0

21.267.8{

116.2610.9
Baseline SBP, mm Hg

Change in SBP, mm Hg

139.9613.6

1.1960.71

20.1160.54{

1.6761.08

20.2160.74{{{
20.2460.64{{

1.7260.89
1.2860.56

0.0060.46
0.0360.56

1.4460.81
1.4760.68

20.0260.50
20.0260.42

1.4560.67
1.0460.62

20.0360.41

1.3860.78
Baseline Tg, mmol/L

Change in Tg, mmol/L

20.0860.47

1.2860.40

0.0160.21
0.0860.21{{{

1.2460.41
1.1760.35

0.0460.16
20.0560.14{{

1.5060.39
1.5060.35

20.0460.20

1.4960.40

20.0160.21
0.0460.12{{{

1.5060.38
1.0960.32

0.0360.13{{{

1.0460.26
Baseline HDL-C, mmol/L

Change in HDL-C, mmol/L

20.0160.21

23.2614.0

31.6616.7
83631

211621{{{
211.6629.1{{{

265.3641.8
82.30640.77

25.58631.33
21.95629.54

70.93641.08
75.85642.34

27.98627.59{
25.2624.9{{{

74641.24
79.7663.2

210.8644.6{{{

65.7640.0
Baseline fasting insulin, pmol/L

22.02631.06

(n#70)
8 kcal/kg/wk
(n#89)

12 kcal/kg/wk
(n#94)
4 kcal/kg/wk
(n#143)

Change in fasting insulin, pmol/L

Data are expressed as means and standard deviations or
standard errors as specified. Intraclass correlations were computed
from the within-subject variance relative to the overall measurement variance. The coefficient of variation is expressed as a
percentage and is derived from the TE relative to the measurement mean. The significance of the gains in VO2max and of the
mean changes in the four targeted risk factors within each cohort
was assessed with paired t tests. The comparisons of VO2max
gains between adverse responders and non-adverse responders for
each risk factor trait for each study was undertaken as follows: The
difference between the changes in VO2max with exercise training
expressed in ml O2 per minute was tested with the general linear

Blacks (n#250)

Statistical procedures

Whites (n#473)

Table 3. Baseline and training-induced changes in the four risk factors for the five cohorts (mean 6 SD).

For the four traits studied, some subjects experienced changes in
an opposite, unfavorable direction compared to the expected
beneficial effects. This is analogous to an AR pattern. Defining an
AR for any given risk factor is a challenge. A robust definition
takes into account the measurement error of the trait, including
the variance among laboratories or laboratory technicians, and the
normal day-to-day biological variation of the trait. The parameter
that captures the totality of these sources of variance in a trait is
known as the technical error (TE), defined as the within-subject
standard deviation as derived from repeated measures (or assays)
over a given period of time, as used in the National Health and
Nutrition Examination Survey (NHANES) [14]. An ancillary
study designed to quantify TE for several biological traits was
undertaken in HERITAGE. Sixty subjects were measured three
times (except for FI) over a period of 3 weeks for each trait
[15,16,17,18,19]. TEs and other useful indicators of reproducibility are shown in Table 1. In the case of FI, the assays were
performed only twice, and we used other HERITAGE data plus
observations from the literature to develop an estimate of TE for
FI (Information S1). Here, we have conservatively defined an AR
as a response beyond 26TE in a direction indicating a worsening
of the risk factor. For the four traits in the present study, twice the
value of TE would mean that ARs would be reached if the exercise
training-induced increases are $10 mm Hg for SBP,
$0.42 mmol/L for plasma TG, and $24 pmol/L for plasma FI
or if there is a decrease of #0.12 mmol/L for HDL-C. These AR
definitions are used in the remainder of this report.

INFLAME

Definition of adverse responses

HERITAGE

Healthy, sedentary 40- to 67-year-old men and women were
recruited [13]. A total of 206 subjects were randomized to one of
four groups. Here we used the data on 25 men and 26 women of
the endurance training group and on 30 men and 24 women (all
Whites) of the combined endurance and strength training group
who exercised for 21 weeks.

DREW

STRRIDE

University of Jyva¨skyla¨ Study (JYVASKYLA)

(n#160)

Maryland

Briefly, 160 men and women (100% Whites) ages 50 to 75 years
who were sedentary, nondiabetic, and nonsmoking, with no prior
history of cardiovascular disease but with one National Cholesterol
Education Program lipid abnormality or blood pressure in the
prehypertensive range, exercised three times per week for a period
of 6 months [12].

Variable

University of Maryland Gene Exercise Research Study
(MARYLAND)

(n#303)

Jyvaskyla

versus resistance training (AT/RT) cohort was very similar to
STRRIDE, but only those who were enrolled in endurance exercise
programs are included in the present report.

(n#105)

Adverse Metabolic Response to Regular Exercise

May 2012 | Volume 7 | Issue 5 | e37887