Exercise in Obesity, Metabolic Syndrome, and Diabetes

Tim Church

Laboratory of Preventive Medicine Research, Pennington Biomedical Research Center Louisiana State University System,
Baton Rouge, LA 70808
Abstract The risk of developing both metabolic syndrome and type 2 diabetes mellitus (T2DM) is
inversely associated with regular exercise training (ET). Excess weight is also strongly
associated with increased risk of both metabolic syndrome and T2DM. There is strong evidence
that even a moderate amount of weight loss achieved through changes in diet and ET can
greatly reduce the risk of developing T2DM.
For the purpose of general health, exercise programs should have both aerobic and resistance
training components. The 2008 federal physical activity (PA) guidelines recommend obtaining
at least 150 minutes per week of moderate-intensity PA, 75 minutes per week of vigorous-
intensity PA, or a combination of the 2. In addition, all individuals should strive for at least 2
days per week of resistance training activity. For the purpose of weight loss, the combination of
ET and reduced energy intake has been found to be more effective than either alone. (Prog
Cardiovasc Dis 2011;53:412-418)
2011 Elsevier Inc. All rights reserved.
Keywords: Obesity; Metabolic syndrome; Diabetes
Approximately 24 million individuals in the United
States have diagnosed or undiagnosed diabetes, with
90% to 95% having type 2 diabetes mellitus (T2DM).
1
The estimated direct and indirect costs of the disease are
$174 billion.
1
Individuals with T2DM have at least
twice the risk for premature death, heart disease, and
stroke compared with individuals without T2DM.
2
Many
of the complications associated with T2DM can be
prevented through regular exercise training (ET), healthy
diet, and weight loss when indicated. The metabolic
syndrome (MetS) is a strong risk factor for T2DM and is
typically defined as the clustering of abnormal levels of
lipids (high-density lipoprotein cholesterol and triglyc-
erides), glucose, blood pressure, and excess abdominal
obesity.
3-6
Given the similarities in pathophysiology
with T2DM, it is not surprising that regular ET and
weight control play a critical role in the prevention and
treatment of MetS.
Despite the widely accepted importance of ET in the
conditions of T2DM and MetS, there remains great debate
about exercise prescription for general health and weight
loss within these conditions. This overview will attempt to
bring some clarity to these issues, specifically examining
the roles of ET and weight loss in preventing and treating
both MetS and T2DM.
MetS, Weight, and ET
The MetS is typically defined as a clustering of
abnormal levels of lipids (high-density lipoprotein cho-
lesterol and triglycerides), glucose, blood pressure, and
excess abdominal obesity. Given that abdominal obesity is
a component of the definition of MetS, it makes sense that
excess weight is a strong risk factor for its development. In
the cross-sectional studies that examined the prevalence of
Progress in Cardiovascular Diseases 53 (2011) 412418
www.onlinepcd.com
Statement of Conflict of Interest: see page 417.

Address reprint requests to Tim Church, MD, MPH, PhD,

Professor, John S. McIlhenny Endowed Chair, Laboratory of Preventive
Medicine Research, Pennington Biomedical Research Center Louisiana
State University System, 6400 Perkins Road, Baton Rouge, Louisiana
70808-4124.
E-mail address: tim.church@pbrc.edu.
0033-0620/$ see front matter 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.pcad.2011.03.013 412
metabolic equivalents
(METs) across levels of
physical activity (PA;
Fig. 1A), all found an
inverse gradient between
amount of PA and
MetS.
7-14
The cross-sec-
tional data support that
obtaining at least 150
minutes per week of
moderate-intensity PA
is associated with a
lower prevalence of
MetS. As depicted in
Fig. 1B, all available
prospective studies that
measured fitness and
categorized participants
based on fitness level show a strong inverse dose-response
between fitness and risk of developing MetS.
15-19
Thus,
despite the methodological differences in assessing PA
through self-report questionnaire and measured fitness, the
association with the prevention of MetS is similar for these
2 modes of PA assessment.
There are numerous studies that have examined the
benefits of ET on individual components of MetS, such as
blood pressure, insulin resistance, and abdominal adipos-
ity, and in general, improvements to the variables of
interest are noted with ET. However, there exist no
published studies that were specifically designed to
examine the efficacy of ET in the reversal of the clinical
diagnosis of MetS.
There are very few studies available that have
examined the role of resistance training (RT) or
quantified muscular strength in the prevention or
treatment of MetS.
20-22
In both cross-section and
longitudinal reports from the Aerobic Center Longitudi-
nal Database, higher levels of muscular strength were
associated with lower risk of MetS.
20,21
However, in the
report using a longitudinal design, the reduced risk of
developing MetS associated with greater levels of
strength was attenuated (34% to 24%) when adjusting
for cardiorespiratory fitness.
21
Though not specifically
addressing MetS, a recent report by Davidson et al
23
demonstrated the relative importance of strength, aerobic,
and combination training on insulin resistance in 136
sedentary, abdominally obese older men and women.
This exquisitely designed and conducted study demon-
strated that although RT improved lean mass and
strength, there was not an improvement in insulin
resistance compared with control (Fig. 2). In contrast,
both the aerobic-only and combination training groups
had significant improvements in insulin resistance. Thus,
in regard to insulin resistance, aerobic ET seems to be the
cornerstone of prevention, with RT providing a small
additional benefit.
Diabetes, ET, and weight loss
There are very strong epidemiologic data demonstrating
that both regular ET and maintaining a healthy weight
greatly reduce the risk of developing T2DM.
24-26
Further-
more, within individuals with T2DM, maintaining higher
levels of fitness is associated with reduced risk of
developing cardiovascular disease (CVD).
27,28
As demon-
strated in Fig. 3, although there is a strong inverse trend for
risk of CVD mortality across levels of fitness; in the lower
levels of fitness, each 1-MET increment is associated with
large differences in risk of CVD mortality. Conversely, in
the moderate to high levels of fitness, the large risk between
associated with 1 MET largely diminishes. In other words,
very low-fit individuals with T2DM stand to benefit
substantially from small increases in fitness.
The strongest evidence to date supporting the impor-
tance of diet, ET, and weight loss in the prevention of
T2DM in individuals at high risk comes from the Finnish
Diabetes Prevention Study and the Diabetes Prevention
Program (DPP).
29,30
Both the Finnish Diabetes Prevention
Study and DPP study were large, long-term, well-
conducted clinical trials examining the benefit of behav-
ioral-based changes in weight in the prevention of
diabetes. For example, the DPP study randomized 3234
at-risk men and women to control, metformin therapy, or
lifestyle modification. The goal of the lifestyle modifica-
tion was at least 7% weight loss through changes in diet
and ET, and this was achieved through intensive
behavioral skill-building strategies. After an average of
2.8 years of follow-up, the incidence of T2DM was 11.0%,
7.8%, and 4.0% across the control, metformin, and
lifestyle groups, respectively. This represented a 58%
reduction in risk of developing T2DM in the lifestyle
group compared with the control group (Fig. 4).
The DPP study was a groundbreaking study that
focused on the importance of lifestyle strategies in
preventing T2DM and is considered to be the predecessor
of the Action For Health in Diabetes study that focused on
examining the role of diet and ET-induced weight loss on
risk of CVD in individuals with T2DM.
31
Although no
CVD outcome data from the Action For Health in Diabetes
trial have been published to date, the intervention data
suggest that long-term changes in PA and weight are
possible in this population.
32
Although most guidelines suggest that individuals with
T2DMs partake in an ET program composed of both
aerobic ET and RT, until recently, there have been
relatively few data exploring the benefits of aerobic ET,
RT, or both in individuals with T2DM.
In 2007, Sigal et al
33
published the findings from the
Diabetes Aerobic and Resistance Exercise, which was
the first adequately powered and controlled study
comparing aerobic training, RT, or both on glycosylated
hemoglobin (HbA1c) in individuals with T2DM. All
exercise groups had a reduction in HbA1c compared
Abbreviations and Acronyms
CVD = cardiovascular disease
DPP = Diabetes Prevention
Program
ET = exercise training
HbA1c = glycosylated
hemoglobin
MET = metabolic equivalent
MetS = metabolic syndrome
PA = physical activity
RT = resistance training
T2DM = type 2 diabetes
mellitus
413 T. Church / Progress in Cardiovascular Diseases 53 (2011) 412418
with the control group, but the combination group had a
larger reduction (1.0%) compared with the RT
(0.4%) and aerobic training (0.5%) groups. However,
the combination-ET group performed both the aerobic
ET and RT (135 and 135 minutes per week, respective-
ly), resulting in approximately 270 minutes per week of
ET. Thus, it is unclear whether the additional benefit
observed in the combination group was due to the
combination of RT and aerobic training or to the extra
time spent exercising.
We recently published our finding from the Health
Benefits of Aerobic and Resistance Training in In-
dividuals With Type 2 Diabetes trial, which was the first
large randomized trial in individuals with T2DM that
compares the benefits of RT, aerobic ET, and the
combination with the aerobic prescriptions that are
consistent with the 2008 Physical Activity Guidelines of
500 to 1000 MET-minutes-week.
34,35
The 2 most
important goals in the development of the ET doses
for the Health Benefits of Aerobic and Resistance
Training in Individuals With Type 2 Diabetes were to
keep the total duration of weekly ET similar across
groups while assuring that the aerobic prescriptions met
the current guidelines. We achieved both goals, as total
time spent exercising across the groups was approxi-
mately 140 min/week, and the aerobic training group
Fig 1. Top panel depicts the risk of having MetS across levels of PA. Bottom panel demonstrates the risk of developing MetS across levels of fitness.
7
414 T. Church / Progress in Cardiovascular Diseases 53 (2011) 412418
and the combined training group performed approxi-
mately 680 and 570 MET/min per week, respectively.
There was a significant reduction in HbA1c in the
group who combined aerobic training and RT compared
with the control group (0.34%). In neither the RT
(0.16%) nor the aerobic ET (0.24%) groups,
however, were changes in HbA1c significant compared
with the control group.
35
The observed a reduction of
0.3% to 0.4% HbA1c might be expected to produce a
5% to 7% reduction in CVD risk and 12% reduction in
risk of microvascular complications. However, subgroup
analysis showed that individuals with elevated baseline
HbA1c (7.0%) had an HbA1c difference of 0.5% to
6%, which would be expected to decrease risk of CVD
events by 7% to 10% and microvascular complications
by 18%. These risk reduction estimates are likely
conservative because they are derived from medication
studies and do not take into account improvements in
cardiorespiratory fitness and strength, as well as
reductions in fat mass and waist circumference, which
should further reduce risk. For example, our findings
that both the aerobic ET and combined aerobic ET and
RT groups had a 1-MET increase in fitness compared
with controls is of great public health significance,
Fig 2. Change in insulin resistance with RT, aerobic training, and the combination of resistance and aerobic training.
23
Fig 3. Risk of cardiovascular mortality in men with diabetes across levels of fitness (METs).
27
415 T. Church / Progress in Cardiovascular Diseases 53 (2011) 412418
given that each MET is associated with 15% to 20%
lower CVD mortality risk.
27,36,37
Exercise prescription for general health and weight loss
As stated in the 2008 Physical Activity Guidelines,
regular ET has meaningful health benefits for individuals
of any weight.
34
These guidelines suggest that individuals
should strive to achieve at least 150 minutes per week of
moderate-intensity PA combined with at least 2 days per
week of RT activity. However, for those that prefer to
participate in vigorous-intensity PA, the minimal weekly
goal is only 75 minutes or more per week.
There is sufficient evidence to conclude that ET
interventions, in the absence of dietary intervention,
produce only modest weight loss. Ross and Janssen
38
reported that in ET interventions of 16 weeks or less (n =
20 studies), the mean weekly weight loss was 0.2 kg, with
a total weight loss of 2.3 kg (5 lb) at follow-up
assessment. The magnitude of weight loss change reported
by Ross and Janssen is nearly identical to those in the
reported in the National Institute of Health Clinical
Guidelines on the identification, evaluation, and treatment
of overweight and obese adults of 2.4 kg (5.3 lb).
39
Ross
and Janssen also reported a dose-response relation
between prescribed caloric expenditure and weight loss
in studies of 16 weeks or less with 85% of expected weight
loss achieved.
38
The dose-response relation was not
observed in studies of 26 weeks or more (n = 12), and
the achieved weight loss was only 30% of expected. Once
again, this demonstrates the need to be cautious when
extrapolating the result of shorter term studies to the longer
term. There are a number of potential causes for longer
term studies failing to produce substantial weight loss,
including small ET doses, poor adherence, and even,
potentially, dietary overcompensation.
40,41
In studies comparing the effectiveness of ET alone to
diet alone, most found diet alone to be more effective than
ET alone in producing weight loss.
39,42-45
This is not
unexpected, given that removing 500 calories from daily
energy intake is relatively less burdensome than expend-
ing 500 calories through ET. However, a number of large
carefully conducted trials have demonstrated that the
combination of ET and dietary intervention has been
found to be more effective than either alone and combined
exercise. For example, examining 201 sedentary, obese
women, Jakicic et al
46
explored the interactions of ET
intensity (moderate vs vigorous) and ET dose (1000 vs
2000 kcal per week) in generating weight loss. All
participants were instructed to reduce calorie intake to
between 1200 and 1500 kcal per day and maintain dietary
fat between 20% and 30% of total energy intake. The 4
intervention groups were moderate intensitymoderate
duration, moderate intensityhigh duration, high intensi-
tymoderate duration, and high intensityhigh duration.
After 1 year of intervention, all 4 groups had a similar
weight lost of loss of approximately 6 kg, with no
statistically significant differences between the groups
(Fig. 5). Although it seemed that the higher ET doses
Fig 4. Results of DPP.
29
416 T. Church / Progress in Cardiovascular Diseases 53 (2011) 412418
achieved greater weight loss (10% vs 7% and 8%)
compared with the lower doses at 1 year, this result was
not statistically significant. The high- and low-intensity
groups had nearly identical results within each ET dose,
suggesting that for a given dose of caloric expenditure,
intensity has no effect on the amount of weight lost. This
study demonstrates that even as little as 1000 kcal per
week of ET, when combined with dietary therapy, can
result in clinically meaningful weight loss.
Although the prescription for ET for general health is
widely accepted, there remains much debate of the
importance and exact prescription of ET for weight loss.
The American College of Sports Medicine Position
Statement entitled Appropriate Intervention Strategies for
Weight Loss and Prevention of Weight Regain for Adults
summarizes the literature and provides solid recommen-
dations for combining diet and ET to promote weight
loss.
45
These guidelines conclude that 150 to 250 minutes
per week of moderate-intensity PA alone will produce
modest weight loss (b3%), but weight loss is greater when
the PA is combined with moderate dietary caloric
restrictions. However, there is a dose-response between
PA and weight loss such that obtaining more than 250
minutes per week of PA is associated with clinically
meaningful weight loss.
Summary
Regular ET has meaningful health benefits for in-
dividuals of any weight. For the purpose of general health,
ET programs should have both aerobic ET and RT
components. The 2008 federal PA guidelines suggest that
individuals should strive to achieve at least 150 minutes
per week of moderate-intensity PA, or for those that prefer
to participate in vigorous-intensity PA, the minimal
weekly goal is only 75 minutes or more per week. All
individuals should also strive for at least 2 days per week
of RT activity. For the purpose of weight loss, the
combination of ET and reduced energy intake has been
found to be more effective than either alone.
Statement of Conflict of Interest
The author declares that there is no conflict of interest.
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