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Physical Activity and Life Expectancy With and Without Diabetes
Life table analysis of
the Framingham Heart Study Jacqueline T. Jonker, MSC1, Chris De Laet,
PHD1, Oscar H. Franco, MD, DSC1, Anna Peeters, PHD2, Johan Mackenbach,
MD, PHD1 and Wilma J. Nusselder, PHD1
1 Department of Public Health, Erasmus Medical Center, University
Medical Center Rotterdam, Rotterdam, the Netherlands 2 Department of
Epidemiology and Preventive Medicine, Monash University Central and
Eastern Clinical School, Melbourne, Australia
Address correspondence and reprint requests to Wilma. J. Nusselder,
PhD, Department of Public Health, Erasmus Medical Center, P.O. Box
1738, 3000 DR, Rotterdam, Netherlands. E-mail: w.nusselder@erasmusmc.nl
OBJECTIVE-Physical
activity is associated with a reduced risk of developing diabetes and
with reduced mortality among diabetic patients. However, the effects of
physical activity on the number of years lived with and without
diabetes are unclear. Our aim is to calculate the differences in life
expectancy with and without type 2 diabetes associated with different
levels of physical activity.
RESEARCH DESIGN AND METHODS-Using
data from the Framingham Heart Study, we constructed multistate life
tables starting at age 50 years for men and women. Transition rates by
level of physical activity were derived for three transitions:
nondiabetic to death, nondiabetic to diabetes, and diabetes to death.
We used hazard ratios associated with different physical activity
levels after adjustment for age, sex, and potential confounders.
RESULTS-For
men and women with moderate physical activity, life expectancy without
diabetes at age 50 years was 2.3 (95% CI 1.2-3.4) years longer than for
subjects in the low physical activity group. For men and women with
high physical activity, these differences were 4.2 (2.9-5.5) and 4.0
(2.8-5.1) years, respectively. Life expectancy with diabetes was 0.5
(-1.0 to 0.0) and 0.6 (-1.1 to -0.1) years less for moderately active
men and women compared with their sedentary counterparts. For high
activity, these differences were 0.1 (-0.7 to 0.5) and 0.2 (-0.8 to
0.3) years, respectively.
CONCLUSIONS-Moderately
and highly active people have a longer total life expectancy and live
more years free of diabetes than their sedentary counterparts but do
not spend more years with diabetes.
Abbreviations: MSLT, multistate life table
INTRODUCTION
The prevalence of diabetes is increasing dramatically worldwide. In
2000, 171 million people worldwide were affected by diabetes. This
number is expected to double by 2030, mainly as a consequence of
population aging and urbanization (1). Type 2 diabetes is associated
with long-term complications and a high burden of morbidity (2,3).
Evidence suggests an inverse association between physical activity and
the risk of developing diabetes (4-11). Physical activity, through
improving insulin sensitivity and glycemic control (12-14), has been
associated with reduced total mortality among diabetic patients (15-20)
and the general population (21). However, the effects of physical
activity on the number of years lived with and without diabetes are
still unclear. Whether, for example, higher levels of physical activity
would reduce the number of years lived with diabetes depends on the
balance of its effect on the risks of developing diabetes and
mortality. For instance, it has been shown that nonsmokers live longer
with cardiovascular disease than smokers because their total life
expectancy is 8 years longer (22). As policy makers increasingly
advocate modification of risk factors with the aim of decreasing
population levels of disease and disability (e.g., 23), it will be
important to analyze the extent to which this is actually the case. The
conundrum is that modification of risk factors, such as smoking and
physical activity, will at the same time decrease disease incidence and
increase survival to advanced age, which is itself one of the strongest
risk factors for disease. Our aim is to quantify the differences in
life expectancy without type 2 diabetes (i.e., the average number of
years lived before the onset of diabetes or death) and life expectancy
with type 2 diabetes (i.e., the average number of years lived with
diabetes) associated with different levels of physical activity.
RESEARCH DESIGN AND METHODS
The Framingham Heart Study cohort consisted of 5,209 respondents (46%
male) aged 28-62 years residing in Framingham, Massachusetts, between
1948 and 1951. The Framingham cohort is primarily white and has been
followed extensively for 46 years for the occurrence of cardiovascular
disease and death through surveillance of hospital admissions, death
registries, and other available medical sources. Examination of
participants, including an interview, a physical examination, and
laboratory tests, has taken place biennially. Further description of
the Framingham Heart Study can be found elsewhere (24).
To calculate transition rates by level of physical activity, we pooled
three nonoverlapping follow-up periods of 12 years. Each follow-up
period started with a measurement of physical activity. In the present
investigation, the follow-up periods started at the original exams 4
(1956-1958), 11/12 (1969-1973), and 19/20 (1985-1989). Using the
pooling of repeated observations method (25), follow-up information
over three follow-up periods was pooled, yielding a total of 9,773
observation intervals. The same participant may thus be followed during
three periods until the event (first onset of diabetes or death) occurs
or the subject is censored. Follow-up time and physical activity status
may differ in each interval. After exclusion of subjects with diabetes
at exam 1 to exclude juvenile diabetes and missing information on
physical activity, we studied 4,176 subjects at exam 4, 3,286 subjects
at exam 11/12, and 1,660 subjects at exam 19/20, yielding a total of
9,122 follow-up observation intervals.
Diabetes assessment
Diabetes was considered present after a random blood glucose level 200
mg/dl or when the subject was treated with a hypoglycemic agent
(insulin and/or oral hypoglycemic agent).
Assessment of physical activity
Participants were asked about their time spent resting or engaged in
light, moderate, or heavy physical activity on an average day. Time
spent at each activity in hours per week was multiplied by its
metabolic cost (based on the oxygen consumption required for that
activity) as described before by Kannel et al. (26). A weight of 1.0
was used for an activity with oxygen consumption of 0.25 l/min, for
example sleep. Other weights were 1.1 for being sedentary, 1.5 for
light activity, 2.4 for moderate activity, and 5 for heavy activity.
The weight factor corresponds to a metabolic equivalent task. These
weighted hours were added up to get a total daily physical activity
score. The minimum physical activity score is 24, which is equivalent
to 24 h of rest/sleep. Based on tertiles of the daily physical activity
scores, we grouped the participants in three levels: low (<30),
moderate (30-33), and high (>33) physical activity level.
Confounders
Potential confounders were measured at the start of each follow-up
period, except for education. All analyses were adjusted for age and
sex. Confounders considered were education (eighth grade or less/higher
than eighth grade), smoking (never, ever, or current smoking), marital
status (single, married, widowed, or separated/divorced), diseases
present at baseline (any of the following: cardiovascular disease,
cancer, left ventricular hypertrophy, arthritis, ankle edema, or any
pulmonary disease), total cholesterol, family history of diabetes
(diabetes in parents and/or siblings), and the exam of start follow-up
(exam 4, 11/12, or 19/20). The exam of start follow-up was included to
correct for a potential cohort and period effect. Hypertension and BMI
were not considered as confounders but as intermediate factors, as
physical activity may cause individuals to have lower BMI and blood
pressure, which in turn reduces the risk of diabetes and mortality.
Adjustment for BMI and hypertension may result in an underestimation of
the true beneficial effect of physical activity. Hypertension was
defined as systolic blood pressure 140 mmHg or diastolic blood pressure
90 mmHg (27). For BMI, four categories were defined: BMI <18.5
kg/m2, 18.5 BMI < 25 kg/m2, 25 BMI < 30 kg/m2, and BMI 30 kg/m2.
Because the information on alcohol consumption was not available for
all follow-up periods, alcohol was excluded from the analyses. For the
final analysis, only participants who had information on all
confounders, BMI, and hypertension were included (3,978, 3,067, and
1,561 subjects at exam rounds 4, 11/12, and 19/20, respectively).
Data analysis
To calculate the life expectancy with and without diabetes, we created
a multistate life table (MSLT) (28). This MSLT, which combines
information of people at different ages and from different birth
cohorts, included three states: "free of diagnosed diabetes,"
"diabetes," and "death." The possible transitions were from free of
diagnosed diabetes to diabetes or to death and from diabetes to death.
No back flows were allowed, and only the first entry into a state was
considered. Age 50 years was chosen as the starting age to include the
effect of physical activity at adult ages, while avoiding unstable
rates due to limited number of events below age 50 years. Another
advantage is that at this age, where the prevalence of type 2 diabetes
is still low, the outcomes of the MSLT for the total and diabetes-free
population are virtually the same.
To obtain transition rates by levels of physical activity, we first
calculated the overall sex- and age-specific transition rates for each
transition (29). Next, we calculated hazard ratios of physical activity
using Poisson regression. We analyzed the effect of potential
confounders on the hazard ratios by first adjusting for age and sex
only and next by including the following in addition: education,
marital status, smoking, baseline diseases, and exam of start
follow-up. Subsequently, adjustments for BMI and hypertension were
added to the previous model to give information about the effect of
these possible intermediates on the hazard ratios. Additionally,
adjusting for BMI did not substantially change the hazard ratios. The
small effect of adjusting for BMI may reflect a small risk of
self-selection of heavy subjects for lower physical activity levels
because physical activity includes physical activity at work. We did
not adjust for total cholesterol (as continuous variable) and family
history of diabetes in the final model, as these variables did not
change the hazard ratios of physical activity and had a large number of
missing values.
Finally, to calculate transition rates by level of physical activity,
we used the overall transition rates, the prevalence of the different
levels of physical activity in the population (stratified by 10-year
age-group, sex, and diabetes), and the hazard ratios of physical
activity adjusted for potential confounding but not for intermediates
(BMI and hypertension).
Separate MSLTs were created for each level of physical activity for men
and women, incorporating each of the three transitions. The MSLT
started at age 50 years and was closed at age 100 years. The measures
available from the MSLT include life expectancy without diagnosed
diabetes (i.e., the average number of years lived free of diabetes
before the onset of diabetes or death) and life expectancy with
diabetes (i.e., the average number of years lived with diabetes) for
populations with either low, moderate, or high physical activity and
free of diabetes at age 50 years.
All statistical analyses were done using STATA version 8.2 for Windows
(Stata, College Station, TX). We calculated CIs for all life
expectancies and differences in life expectancies using Monte Carlo
simulation (parametric bootstrapping) (30). To calculate the CIs, we
used @RISK (Anonymous 2000; MathSoft) 10,000 runs.
In the categories low and moderate physical activity, the proportion of
women was higher than in the category with high physical activity (63
and 62%, respectively, compared with 46%) (Table 1). Participants in
the low physical activity group tended to be older (mean age 62 years)
compared with the participants of the moderate and high activity groups
(mean age 58 and 59 years, respectively); also, the level of baseline
diseases was higher among participants with low physical activity.
Blood pressure and total cholesterol showed a tendency toward an
inverse relationship with physical activity (Table Table 1- Baseline
characteristics by physical activity level*
Risk of diabetes and death
Higher levels of physical activity were associated with lower rates of
incident diabetes (corrected for age and sex) (online appendix
[available at http://care.diabetesjournals.org]). After additional
correction for selected confounders, the effect slightly increased and
the hazard ratio remained significant Table 2- Hazard ratios for the
different transitions The risks of mortality in subjects without
diagnosed diabetes (corrected for age and sex) were inversely related
to the level of physical activity (Table 2). Correcting for confounders
slightly attenuated the effect, but all hazard ratios remained
significant. The mortality rates in subjects with diabetes were also
lower in active subjects than in sedentary subjects. After adjusting
for confounders, this association was only significant for high
physical activity.
Total life expectancy and life expectancy with and without diabetes
Figure 1 shows survival curves, total and free of diabetes, by level of
physical activity. The area under these survival curves is total life
expectancy and life expectancy without diabetes, respectively. The
difference between the total and diabetes-free life expectancy is life
expectancy with diabetes. At age 50 years, total life expectancy was
27.2 (men) and 33.8 (women) years, of which 25.5 and 32.1 years,
respectively, were spent without diabetes and 1.7 years (both sexes)
with diabetes. In contrast, life expectancy of 50-year-old individuals
with diabetes is 23.8 and 24.3 years for men and women, respectively.
Figure 1- A:
Survival curves illustrating the probability of surviving with age by
sex for different levels of physical activity (low, moderate, and
high). The area under the survival curve is the total life expectancy
for populations with low, moderate, or high physical activity and free
of diabetes at age 50 years. B: Survival curves illustrating the
probability of surviving free of diabetes with age by sex for different
levels of physical activity (low, moderate, and high). The area under
the survival curve is life expectancy without diabetes for populations
with low, moderate, or high physical activity and free of diabetes at
age 50 years.
Life expectancy of 50-year-old men in the moderate and high activity
groups was 1.8 (95% CI 0.8-2.9) and 4.1 (2.8-5.4) years longer,
respectively, than of men in the lowest activity group. For women,
these differences were similar: 1.7 (0.8-2.8) and 3.7 (2.6-4.9) years
(Table 3). This larger total life expectancy was composed of more years
lived without diabetes and fewer years lived with diabetes. Both
moderately active men and women lived 2.3 (1.2-3.4) more years without
diabetes than those in the lowest activity group (Table 3). In the
highest activity group, men and women lived 4.2 (2.9-5.5) and 4.0
(2.8-5.1) years longer, respectively, without diabetes than their
sedentary counterparts. Moderately active men and women lived 0.5 (men:
95% CI -1.0 to 0.0, women: -1.1 to -0.1) years less with diabetes,
compared with those with low physical activity. For high activity
groups these differences for men and women were 0.1 and 0.2 years,
respectively, but were no longer significant (Table 3).
Table 3- Life expectancy in years at age 50 years for three levels of physical activity*
CONCLUSIONS
Moderately and highly active people live longer and spend more years
without diabetes than subjects with low physical activity levels. At
age 50 years, life expectancy free of diabetes is 2.3 years longer for
moderately active men and women and at least 4 years longer for highly
active men and women. The effect of physical activity on life
expectancy without diabetes reflects both the lower incidence of
diabetes and the lower mortality of nondiabetic individuals associated
with increasing physical activity levels. Life expectancy with diabetes
is at least 0.5 and 0.1 years less for moderate and highly active
people, respectively, compared with those with low physical activity.
This reflects two opposing effects: 1) lower incidence of diabetes in
the active group reducing the time spent with diabetes and 2) lower
mortality in diabetic subjects, increasing the time spent with
diabetes. The net result is that while moderate and highly active
people live longer, they do not spend more years with diabetes. The
reported hazard ratios found in our study fall well within the range of
the published measures of the effect of physical activity on incident
diabetes (4-6,8,9,31-33) and mortality of diabetic subjects
(15,16,19,20). However, comparison with prior studies is difficult
because the measurement scales and definitions of physical activity
used differ. Most studies published on the subject (4,6,8,9,31,32) have
found dose-response relations between physical activity and the
incidence of diabetes. We similarly found a dose-response relation
between physical activity and the mortality rates among nondiabetic and
diabetic subjects. However, similar to a few other studies (5,33,34),
we found that the degree of protection against diabetes was virtually
the same in those with either vigorous or moderate physical activity
levels. Additional analyses (data not shown) suggest that, in
particular, the oldest subjects are responsible for this lack of a
clear dose-response relation. Our data suggested that the effect of
physical activity could be different in those aged >80 years. A
possible explanation is that at this age, the lower physical activity
group still at risk for diabetes is more selected due to higher risks
of diabetes and mortality earlier in their life than those with higher
levels of physical activity. However, the study was underpowered to
detect any true difference in effect, and it is unlikely that such a
difference would have affected our conclusions. Similar to Gregg et al.
(20), the effect of moderate physical activity on the transition of
diabetes to death did not reach statistical significance after full
adjustment. Additional analyses showed that using a hazard ratio of
1.00 for this transition in the moderate active group would only
strengthen our results.
A strength of this study is the use of data from a prospective,
well-organized study, with long-term follow-up. Another advantage is
that the glucose levels as well as other risk factors are measured at
regular, biannual intervals. In our study, diagnosis of diabetes was
based on glucose tests or the use of hypoglycaemic agents instead of
self-report. In studies based on self-reported diabetes, many subjects
with diabetes remain undiagnosed. In this study, there could be
underdiagnosis only if subjects were not present at one or more exams
(or had a false-negative test). As most subjects only missed one or a
few subsequent exams, it becomes more a matter of delayed diagnosis
than underdiagnosis.
Some limitations should be mentioned. The present study is an
observational study and not a randomized trial. Consequently, bias may
occur if diseases at baseline are responsible for inactivity (reverse
causation) and if other factors confound the association between
physical activity and the transition rates. There are two approaches to
avoid reverse causation: exclusion of subjects with known diseases at
baseline or adjustment for baseline diseases in the analysis. We used
the second option, since we considered that by excluding subjects with
diseases at baseline, there would be a selection of healthy people, and
therefore the results would not be applicable to the whole population.
Residual confounding cannot entirely be ruled out, but as we examined
the potential effect of a large set of confounders (age, sex,
education, presence of diseases, marital status, smoking, exam of start
follow-up, cholesterol, and family history of diabetes) and included
those that affected the association between physical activity and the
transitions, we do not expect that this would have biased our results.
Another limitation of our study is that in the Framingham Heart Study,
physical activity levels were evaluated by self-report, which may
introduce misclassification of exposure. However, this
misclassification is likely to be nondifferential, which can only
attenuate our results and fade a stronger association. We maximized the
power of our study by using 12 years of follow-up. As a long period of
follow-up reduces the effect of selection, but increases the risk of
misclassification of exposure, the optimal follow-up time is unknown.
Since it has been reported that levels and effects of physical activity
change with time (35), we evaluated the effect of length of follow-up
on the relation between physical activity and the transitions. These
sensitivity analyses showed that with a follow-up period of 8 or 10
years instead of 12 years, our main conclusions did not change (data
not shown).
The added value of this study is the combination of the observed
effects of physical activity on incidence of diabetes and mortality in
a large prospective study and the translation into the population
health measures (life expectancy with and without diabetes). This study
shows that physically inactive people have shorter lives, and,
moreover, they live fewer years without diabetes and more or an
equivalent number of years with diabetes compared with people with
higher levels of physical activity. These results underline the public
health importance of increasing physical activity levels in the
population. Moreover, as Reunanen et al. (2) found that total costs of
medications for people with diabetes were 3.5 times greater than those
for nondiabetic control subjects, our findings are also important for
the health care sector. When people live longer, but do not spend more
years with diabetes, they do not put an extra demand on
diabetes-related health care.
As far as the associations reflect causal relationships, our study
suggests that if sedentary people could be stimulated to be at least
moderately active, they could extend their lives and increase their
lifetime spent without diabetes without spending more years with
diabetes.
Acknowledgments
This study was supported by grants from the Netherlands Organization
for Scientific Research (ZON-MW grants 014-91-054 and 904-68-493) and
part of the Master of Science Program in Public Health at the
Netherlands Institute for Health Sciences. The authors acknowledge the
Framingham Heart Study coordinators for access to the original dataset.
The Framingham Study is conducted and supported by the National Heart,
Lung, and Blood Institute (NHLBI) in collaboration with the Framingham
Heart Study investigators. This manuscript has been reviewed by NHLBI
for scientific content and consistency of data interpretation with
previous Framingham Heart Study publications and significant comments
have been incorporated prior submission for publication. We also thank
Jan Barendregt for his assistance in making confidence intervals with
@risk.
Footnotes Additional information for this article can be found in an online appendix at http://care.diabetesjournals.org.
A table elsewhere in this issue shows conventional and Système
International (SI) units and conversion factors for many substances.
Received for publication May 31, 2005. Accepted for publication September 30, 2005.
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