December 6 — 7, 2007 Advisory Committee Meeting
Metabolic Health Subcommittee Report
Judith Regensteiner, Ph.D. led the presentation of the Metabolic
Health Subcommittee report. Dr. Regensteiner outlined the presentation with the
five questions the subcommittee developed:
Can physical activity prevent diabetes?
What is the relationship between physical activity and
prevention of Type 2 Diabetes?
Is there a relationship between physical activity and Type 2
If there is a relationship between physical activity and Type
2 Diabetes what is the dose-response relationship?
What is the relationship between physical activity and Type 2
Diabetes in adults, youth, men, women and ethnic groups and are the
relationships different among these groups?
It is known that physical activity and exercise has metabolic
and cardiovascular benefits for diabetes. While there are studies that indicate
physical activity can prevent Type 2 Diabetes it is important to note that
there are not a lot of studies. Due to this fact it will also be important for
this committee to highlight what is not know and what needs further work.
Both observational and randomized control studies have addressed
the interaction between diabetes, physical activity and exercise. Most
randomized controlled trials have used a combination of life-style treatments
including diet and exercise which makes it harder to ascertain the benefits of
exercise alone. Observational epidemiological studies using self-report
mechanisms such as questionnaires have consistently shown the benefit of higher
levels of physical activity towards the prevention of diabetes.
Three major randomized controlled trials have addressed the
independent effect of effect of physical activity in as much as they were able.
Two studies, the Finnish Diabetes Prevention study and the American Diabetes
Prevention Program (DPP) both had a lifestyle arm including both exercise and
diet. The Ching study in China included an exercise alone arm. Due to the
extreme complexity of such trials and the cost associated it has been generally
deemed not as effective to conduct studies using exercise only arms.
The DPP study found weight loss as the dominant predictor of
reduced incidence of diabetes; however, physical activity and diet did predict
weight loss. In many such studies when comparing individuals who did not lose
weight compared to individuals that achieved their physical activity goal there
was a 44% lower incidence of diabetes even though they did not lose weight. This
would seem to conclude that physical activity itself does have a protective role
When trying to determine the appropriate dose of exercise one
can conclude a specific amount of activity will have benefit in preventing
diabetes; however, it is difficult to determine whether a lower or higher dose
would have better results. While determining the appropriate dose is problematic
one can conclude that there is strong evidence that physical activity has a
major role in preventing Type 2 Diabetes as well as cardiovascular events and
mortality. It seems consistent in men and women as well as along ethnic groups
from the existing studies available but more data could lead to more powerful
conclusions. The results in youth are now pending from the Today Study.
The second question addressed by the subcommittee, "what is the
relationship between physical activity and gestational diabetes (GDM)," is a
very important area due to the rising levels of obesity in the population. No
randomized controlled trials have prospectively assessed whether physical
activity can prevent GDM. Observational studies do seem to support the benefits
of physical activity in reducing GDM. One such study conducted by Jennifer
Dempsey, an obstetrician, seemed to conclude that 30 minutes of exercise five
times a week yields benefits. Overall, more studies and data is needed in this
area in order to produce a strong evidence based conclusion.
Dr. Regensteiner then introduced Dr. Timothy Church to address
the metabolic syndrome and whether physical activity can prevent the metabolic
syndrome. Metabolic syndrome is important to address because it can put
individuals at high risk for diabetes, cardiovascular disease and premature
Dr. Church referenced several studies in which the majority of
which supported the fact that physical activity prevents metabolic syndrome. One
study, the Kuopio Study focusing on eschemic heart disease looked at both
physical activity and fitness is important to note because it shows a true
dose-response relationship. A weakness of the study is the fact that it only
looked at men. Also, there are no exercise studies that focused exclusively on
the treatment of metabolic syndrome. The Heritage Study, which was an
uncontrolled study, analyzed fitness and genes in association with a host of
risk factors. Most of the outcomes in this study showed the improved benefits of
20 weeks of aerobic exercise. In summary, there is an inverse association
between physical activity level and the development of the metabolic syndrome.
The association appears to be dose-response and not threshold in nature.
Dr. Regensteiner next introduced Dr. Amy Huebschmann to address
the prevention of complications of diabetes and Type 1 Diabetes. Outlining her
remarks, Dr. Huebschmann noted she will be specifically discussing the role of
physical activity in the prevention of microvascular complications and when
possible note a dose-response relationship and any differences between genders.
The following specific complications were reviewed: nphropathy,
neuropathy and the attendant problems associated with neuropathy progression
including ulcers, fall risk and retinopathy. There are very few randomized
studies that have looked at the complications in relation to physical activity.
With regards to neuropathy, one randomized trial in both Type 1 and Type 2
Diabetes was positive. Additionally, in Kriska's work (males only), there was a
reduction in the instance of neuropathy and a case control study was negative.
With regards to nephropathy, one out of the four observational studies was
positive in both men and women. An additional study at Kriska was positive for
reduction of nephropathy in men only. Two cross-sectional studies were negative.
For retinopathy, only one of the seven studies showed benefit, which may
indicate a lower benefit in this condition. In conclusion the evidence for
primary prevention is poor to fair; however, it does suggest a possible
relationship between the primary prevention of neuropathy and nephropathy and
certainly no increased risk of retinopathy. In the area of secondary prevention
we are also limited by the amount of data available to study but similarly to
primary prevention there seems to be a possible beneficial relationship.
Dr. Huebschman next reviewed the sub-committees review of the
relationship between physical activity and prevention of cardiovascular
complications. One meta-analysis summarizing over 1,000 subjects with Type 2
Diabetes compared the effects of three different types of training regimen,
either an aerobic training regimen, a resistance strength training regimen or
combined aerobic and strength training. The results indicate that all three
methods of training improved insulin sensitivity with greater effects from
combined training, followed by aerobic and then resistance training. Additional
cardiovascular risk factors were improved in both the combined training regimen
and aerobic training regimen but not the resistance training regimen. Also, a
study linking the NHANES database physical activity data to the National Death
Index showed that more than two hour per week of walking was associated with a
41% reduction in cardiovascular mortality. More than two hours per week was
associated with a 30% reduction. Studies such as the Nurses Health Study shows a
significant dose-response, although it is undetermined whether the dose-response
flattens out at greater levels of exercise.
In conclusion, the role of exercise in reducing cardiovascular
risk seems particularly beneficial in individuals with Type 2 Diabetes and
impaired glucose tolerance as compared with individuals who are normal glycemic.
Dose-response would suggest that greater than 120 minutes per week of exercise
is optimal and that aerobic or combined aerobic and resistance exercise would be
best. Further data would be beneficial to determine if there are differences
Finally, Dr. Huebschman discussed the relationship between
physical activity and the prevention of Type 1 Diabetes. As there is no known
relationship with regards to primary prevention the sub-committee focused on the
benefits to secondary prevention. In terms of glycemic control there are many
small interventional studies which are roughly split 50/50 as to whether
physical activity has a benefit. A few larger cross-sectional studies show
similar modest reductions. Safety and exercise should also be discussed along
with Type 1 Diabetes. The benefits of physical activity in this area come at the
expense of increased risk of hypoglycemia. Normal protection from hypoglycemia
in normal subjects comes from counter-regulatory hormones. Individuals with Type
1 Diabetes adjust less so there is risk of bottoming out on sugars.