Type 2 Diabetes Is a Preventable Disease-Lifestyle Is the Key

Abstract

Type 2 diabetes is increasing rapidly all over the world. Since it develops from an interaction between genes and lifestyle factors, it can also be prevented by influencing its modifiable risk factors. During the last two decades, several well-designed and properly conducted controlled trials have confirmed that lifestyle intervention is highly effective in preventing type 2 diabetes in high-risk individuals. Such trials have been carried out in many different populations and living environments – all of them producing similar beneficial effects. Moreover, long-term follow-up of the participants in such trials has revealed that these benefits are sustaining long after the actual intervention has been stopped. It is however likely that different people benefit from different interventions, and this may partly depend on their genetic constellations. The results from these trials must now be applied in the real-life settings in order to stop the pandemic of type 2 diabetes. It is well known that obesity, unbalanced diet and physical inactivity are the major risk fac-tors for type 2 diabetes (T2D). 1 In genetically predisposed people the probability to develop T2D is very high once exposed to "unhealthy" lifestyles. The development of T2D is a slow process during which only subjects that carry a genetic predisposition may develop T2D. About half of individuals will develop T2D during their lifetime, and up to 30-35% will have impaired glucose tolerance (IGT). 2,3 Even though genetic effects are important for the development of T2D 4 and increasing number of T2D susceptibility genes are known, 5 it is not possible to modify them. Until recently, evi-dence regarding the prevention of T2D based on proper randomized controlled trials (RCT) was virtually missing, but today this knowledge gap is filled and there is unequivocal and strong evidence that we can prevent the pro-gression to T2D diabetes in high-risk individuals with lifestyle intervention. Lifestyle Trials in People with IGT to Prevent Progression to Type 2 Diabetes The feasibility of diet and exercise intervention in men with IGT was assessed in Swedish men. 6 Since the reference group comprised of men who did not want to join the intervention, the groups were not randomly assigned. During the 5-year study 11% and 29% of the inter-vention and reference groups developed diabetes, respectively. In Da-Qing China subjects with IGT were assigned either to a control, or lifestyle inter-vention groups using a cluster-randomized trial design. 7 The cumulative 6-year incidence of type T2D was lower in the three intervention groups (41-46%) than in the control group (68%).

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Journal of Medical Sciences (2010); 3(2): 82-86 Review Article
82
Open Access
Type 2 Diabetes Is a Preventable Disease - Lifestyle Is the Key
Jaakko Tuomilehto1,2,3
1Hjelt Institute, Department of Public Health,
University of Helsinki, Helsinki, Finland
2South Ostrobothnia Central Hospital, Seinajoki,
Finland
3Department of Clinical and Preventive
Medicin, Danube-University Krems, Krems,
Austria
Abstract
Type 2 diabetes is increasing rapidly all over the world.
Since it develops from an interaction between genes and
lifestyle factors, it can also be prevented by influencing its
modifiable risk factors. During the last two decades,
several well-designed and properly conducted controlled
trials have confirmed that lifestyle intervention is highly
effective in preventing type 2 diabetes in high-risk
individuals. Such trials have been carried out in many
different populations and living environments – all of them
producing similar beneficial effects. Moreover, long-term
follow-up of the participants in such trials has revealed
that these benefits are sustaining long after the actual
intervention has been stopped. It is however likely that
different people benefit from different interventions, and
this may partly depend on their genetic constellations. The
results from these trials must now be applied in the real-life
settings in order to stop the pandemic of type 2 diabetes.
Correspondence
JAAKKO TUOMILEHTO
Mannerheimintie 172, 00014
University of Helsinki
Helsinki, Finland
Tel: +358 40 5016316
Fax: +358 20 6108661
E-mail: jaakko.tuomilehto@helsinki.fi
Keywords: Controlled trials, lifestyle intervention, obesity, prevention, type 2
diabetes.
It is well known that obesity, unbalanced diet
and physical inactivity are the major risk fac-
tors for type 2 diabetes (T2D).1 In genetically
predisposed people the probability to develop
T2D is very high once exposed to "unhealthy"
lifestyles. The development of T2D is a slow
process during which only subjects that carry a
genetic predisposition may develop T2D.
About half of individuals will develop T2D
during their lifetime, and up to 30-35% will have
impaired glucose tolerance (IGT).2,3 Even
though genetic effects are important for the
development of T2D4 and increasing number
of T2D susceptibility genes are known,5 it is not
possible to modify them. Until recently, evi-
dence regarding the prevention of T2D based
on proper randomized controlled trials (RCT)
was virtually missing, but today this knowledge
gap is filled and there is unequivocal and
strong evidence that we can prevent the pro-
gression to T2D diabetes in high-risk individuals
with lifestyle intervention.
Lifestyle Trials in People with IGT to Prevent
Progression to Type 2 Diabetes
The feasibility of diet and exercise intervention
in men with IGT was assessed in Swedish men.6
Since the reference group comprised of men
who did not want to join the intervention, the
groups were not randomly assigned. During
the 5-year study 11% and 29% of the inter-
vention and reference groups developed
diabetes, respectively.
In Da-Qing China subjects with IGT were
assigned either to a control, or lifestyle inter-
vention groups using a cluster-randomized trial
design.7 The cumulative 6-year incidence of
type T2D was lower in the three intervention
groups (41-46%) than in the control group
(68%).

TYPE 2 DIABETES IS A PREVENTABLE DISEASE Journal of Medical Sciences (2010); 3(2)
83
The Finnish Diabetes Prevention Study (DPS)
provided the first convincing evidence from a
proper RCT that T2D can be prevented by
lifestyle modification.8 Persons with IGT were
randomized to intensive lifestyle intervention
had a 58% lower T2D incidence than the con-
trol group during an average 3.2-year follow-
up,. The lifestyle intervention goals were l)
reduction in weight of 5 %, 2) total fat intake
<30 % of energy, 3) saturated fat intake <10 %
of energy, 4) fibre intake 15g/1000 kcal, and
5) moderate exercise for 30 minutes/day.
During the first year body weight decreased
significantly more in the intervention group,
and also all indicators of the metabolic syn-
drome were all reduced significantly.9
The US Diabetes Prevention Program (DPP)10
also recruited individuals with IGT who were
randomized to receive intensive dietary and
exercise counseling, metformin, or placebo.
The risk reduction after 2.8 years was 58% in the
lifestyle intervention group compared with the
placebo group; metformin showed 35% risk
reduction. In the Indian DPP11 people with IGT
were randomized into four groups (control,
lifestyle modification, metformin, and com-
bined lifestyle modification and metformin.
After median follow-up of 30 months, the
relative risk reduction in T2D diabetes inci-
dence was with lifestyle modification, 26.4%
with metformin and 28.2% with lifestyle modifi-
cation and metformin, as compared with the
control group. Thus, there was no added
benefit from combining the pharmacologic
and lifestyle interventions. The Japanese trial12
included IGT men randomized to receive
either intensive lifestyle or standard interven-
tion. The 4-year incidence of T2D was 67%
lower in the intervention group than control
group.
Long-Term Effectiveness of Lifestyle Prevention
of Type 2 Diabetes in People with IGT
The trials listed above have demonstrated the
benefits of healthy lifestyle on delaying the
deterioration of glucose tolerance to manifest
type 2 diabetes, at least as long as the
intervention continued. Data on possible long-
term effects of such active lifestyle counseling
are accumulating. The Malmo study13 revea-
led that 12-year mortality among men in the
former IGT intervention group was lower than
in the control group (6.5 vs. 14.0/ 1000 person-
years, p = 0.009).
In a median 7-year follow-up of the DPS the
marked reduction in type 2 diabetes inci-
dence was sustained.14 More importantly, after
median 3-year post-intervention follow-up
group, type 2 diabetes incidence was 4.6 and
7.2 per 100 person-years, in the intervention
and control groups, respectively (log-rank test
p=0.0401), i.e. a 36% additional risk reduction.
The absolute risk difference between groups
increased during the post-intervention period:
intensive lifestyle intervention for a limited time
can yield long-term benefits on type 2 dia-
betes risk in individuals with IGT.
The 20-year follow-up of the original Da Qing
cohort showed that a lower type 2 diabetes
incidence persisted in the lifestyle intervention
groups compared with control participants.
The risk reduction remained essentially the
same also during the post-intervention pe-
riod.15 They also observed that cardiovascular
mortality tended to be lower (17%) among
those who had received lifestyle intervention.
Recently, also the US DPP investigators repor-
ted sustained reduction in l0-year incidence of
T2D in the lifestyle intervention group, parti-
cularly in people who were aged >60 years at
baseline.16
Clinical Trial Evidence of the Effect of Lifestyle
Factors on Type 2 Diabetes Risk
In most of the published prevention trials the
main aim was to see if comprehensive lifestyle
intervention reduces T2D risk. In the DPS the risk
reduction of diabetes was strongly associated
with the number of lifestyle goals achieved.8
Success in achieving the intervention goals in
the DPS was estimated from the food records
and exercise questionnaires. The success score
(from 0 to 5) was calculated as the sum of
achieved lifestyle goals. There was a strong
inverse correlation between the success score
and the incidence of diabetes during the total

Journal of Medical Sciences (2010); 3(2) JAAKKO TUOMILEHTO
84
follow-up. This was especially apparent when
the success in achieving the goals was asse-
ssed at year 3, which probably reflects the
importance of sustained lifestyle changes.14
The hazard ratios were 1.00,0.87,0.67, 0.70 and
0.23, for success score from 0 to 4-5,
respectively (p for trend <0.001).
The effects of various components of interven-
tion are interesting and therefore some post-
hoc analyses related to this issue was comp-
leted. The independent effects of achieving
the success score components at 3-year exa-
mination was assessed by including each of
the five lifestyle goal variables individually in a
Cox model. Univariate hazard ratios for
diabetes incidence (95% CI) were 0.45 (0.31-
0.64) for weight reduction from baseline, 0.65
(0.45-0.95) for intake of fat, 0.59 (0.31-1.13) for
intake of saturated fat, 0.69 (0.49-0.96) for
intake of fiber, and 0.62 (0.46-0.84) for physical
activity, comparing those who did or did not
achieve the respective goal. Furthermore,
weight change was significantly associated
with the achievement of each of the other
four lifestyle goals, and consequently, success
score was strongly and inversely correlated
with weight reduction.17 These findings suggest
that dietary composition and physical activity
are important in diabetes prevention but their
effect on diabetes risk is primarily mediated
through resulting weight reduction. Neverthe-
less, due to multicolinearity, the interpretation
of the results should be done cautiously. It
should also be noted that in the Indian IDPP11
and Chinese prevention study 7 the partici-
pants were relatively lean and there was no
large change in body weight, but despite that
a remarkable reduction in diabetes risk was
apparent. Thus, in these studies components of
the intervention other than weight control
were responsible for the beneficial effects on
diabetes risk.
Modifying Effects of T2D Susceptibility Genes
Although T2D susceptibility genes cannot be
manipulated, they can modify the effect of
lifestyle intervention. Thus, they can either
reduce or increase the effect of various
lifestyle changes. In the DPS modifying effects
of a large number of such genes has been
tested. Some, but not all of them seem to
interact with lifestyle intervention.18-31
Comment
While T2D prevention trials rigorously defined
populations by explicitly characterizing their
glycaemic status, these studies did not include
all groups at risk for developing TD Methods
that can also define other groups at high risk
for developing T2D have been recently deve-
loped and are increasingly used in several
countries.32 The recent analysis of the DPS has
also shown that high-risk people identified by a
simple diabetes risk score will significantly
benefit from lifestyle interventions.14
A prospective study based on the data from
the UK estimated the association between the
achievement of the five lifestyle goals used in
the DPS and the T2D risk developing diabetes
during a 4.6-year follow-up.33 The incidence of
diabetes was inversely related to the number
of goals achieved (p<0.001). None of the
participants who met all five of the goals [0.8%
of the total population] developed diabetes,
whereas the risk of diabetes was highest in
those who did not meet any of these goals. If
the entire population were able to meet one
more goal, the total incidence of T2D is
predicted to decrease by 20%. This finding
suggests that health promotion interventions
that result in an increase in healthy lifestyle in
the general population might significantly re-
duce the growing burden of type 2 diabetes.
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