The goals of our clinical
research are
- to establish the most
effective exercise prescription in health and disease
- to understand the
mechanisms in which exercise/physical activity prevents and treats
modern chronic disease
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2011-12
Clinical Exercise Physiology Lab Team
Dr. Barbara Campaigne, Andrew Zabel, Anna Gabbard, Chad Wiggins, Sylvanna Bielko, Ning Ding, Dr. Janet P. Wallace, and Saurabh Thosar.
Not Pictured: , Dr. James Klaunig, Dr. John Watkins, III, and Dr. Kieren Mather.
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In the past, we have focused on hypertension and obesity. Currently, diabetes is the focus of our research. We are challenging the existing diabetes treatment paradigm with the concept of the importance of postprandial endothelial function as a specific target for the prevention of atherosclerotic cardiovascular disease in type 2 diabetes.
The measurement of endothelial
function is a new direction for our laboratory. We
are applying this measurement of artery health to the postprandial
period for the purpose of studying the effects of physical activity
on the postprandial endothelial dysfunction. |
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RESEARCH
IN ENDOTHELIAL FUNCTION |
In 2005, our research
focus reached a new level with the incorporation of the measurement
of Brachial Artery Flow-Mediated Dilation (FMD). In the past, our
disease outcomes were classic risk factors for atherosclerotic cardiovascular
disease; i.e. cholesterol, blood pressure, and/or blood sugar. With
our new technology, we can now observe the nature of a single layer
of cells in the artery, the endothelium. The endothelium is the
site where atherosclerotic cardiovascular disease begins. The endothelium
is responsible for maintaining vascular functions that protect the
artery from disease. Life-style factors, such as diet or smoking,
insult the endothelium compromising its ability to protect the artery,
leading to heart disease, stroke, and peripheral vascular disease.
A simple illustration
of the measurement of endothelial function using the flow-mediated
dilation of the brachial artery is below. |
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Since 2004, our research has focused on the effectiveness of physical activity to protect the vascular endothelium from lethal postprandial atherosclerotic stress. Our work includes:
We have also conducted studies directly investigating the FMD technique:
We have published (including several in press) 11 research and 2 review papers reflecting the evolution of our research on endothelial function in the last six years.
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OUR CURRENT RESEARCH DIRECTION
Our most current research, has been funded by the Indiana Clinical and Translational Institute located with the Medical School on the Indianapolis campus. We have applied to the National Institutes of Health and the American Diabetes Association for funding in this area. Fundamentally, we challenging the existing diabetes treatment paradigm with the concept of the importance of postprandial endothelial function as a specific target for the prevention of atherosclerotic cardiovascular disease in type 2 diabetes.
Despite the existence of strong correlations between glycemic control and atherosclerotic cardiovascular disease (ACVD) in type 2 diabetes (DM2) tight glycemic control did not achieve the expected reduction in ACVD. In fact, one such trial (ACCORD) was terminated prematurely because of an unexpectedly higher incidence of cardiovascular mortality in the “tight control” group. Medications that lowers overall glucose were utilized in these clinical trials. Whereas, we believe the cause of cardiovascular disease is more related to the postprandial glycemia and lipemia than overall glycemic control (HbA1c). We propose prevention of cardiovascular disease in DM2 should focus on control of both glycemic and lipemic elevations following a meal.
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We propose to compare effects of improved endothelial function and postprandial endothelial function using two differing approaches (adding a GLP-1 agonist or physical activity to metformin), targeting similar overall effects on meal-related glycemic and lipemic excursions for 12 weeks in DM2.
Approximately 12 DM2 patients who are in moderate glycemic control (HbA1c 7.5-8.5%) will be randomly assigned to 12 weeks of physical activity + metformin or GLP-1 agonist + metformin. Separate oral high-sugar and high-fat loads will be presented before and after treatment. Biomarkers of oxidative stress and endothelial function will be measured with glycemic load at baseline, 1 and 2 hours following the high-sugar meal; and with lipemic load at baseline, 2 and 4 hours following the high-fat meal.
This study begins recruiting subjects in January 2012.
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INFLUENCE OF RETROGRADE AND ANTEGRADE FLOW ON ENDOTHELIAL FUNCTION |
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In his dissertation, Blair Johnson observed the influence of higher retrograde flow on endothelial function during rest and exercise.
Subjects engaged in supine cycling with one arm serving a the control and the other manipulated to produce a dose response of antegrade flow. A blood pressure cuff was inflated to 30, 45 and 60 mm Hg to produce three different does of retrograde flow.
The brachial artery FMD between arms was compared to determine the influence of the retrograde flow on endothelial function. |
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Our
recent publications in endothelial function include:
- Johnson, B.D., J. Padilla, and J.P. Wallace. The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men. European Journal of Applied Physiology, 112:33-42, 2012.
- Johnson, B.D, K.J. Mather, and J.P. Wallace. Mechanotransduction of Shear in the Endothelium: Basic Studies and Clinical Implications. Vascular Medicine, 16:365-377, 2011
- Patel, Y.R., K.A. Han, A.A. Lteif, J.P. Wallace and K.J. Mather. A cross-sectional evaluation of seasonality as a determinant of endothelial function. Nitric Oxide, in press (on line now).
- Johnson, B.D., J. Padilla, R.A. Harris, J.P. Wallace. Vascular consequences of a high-fat meal in physically active and inactive adults. Applied Physiology, Nutrition and Metabolism 36:368-375, 2011.
- Wallace, J.P. B. Johnson, J. Padilla and K. Mather. Postprandial lipemia, oxidative stress, and endothelial function: A review. International Journal of Clinical Practice, 64:398-403, 2010
- Padilla, J., B.D.
Johnson, S.C. Newcomer, D.P. Wilhite, T.D. Mickleborough, A.D.
Fly, K.J. Mather, and J.P. Wallace. Adjusting flow-mediated dilation
for shear stress stimulus allows demonstration of endothelial
dysfunction in a population with moderate cardiovascular risk.
Journal of Vascular Research. 46:592-600, 2009.
- Padilla, J., B.D.
Johnson, S.C. Newcomer, D.P. Wilhite, T.D. Mickleborough, A.D.
Fly, K.J. Mather, and J.P. Wallace. Normalization
of flow-mediated dilation to shear stress area under the curve
eliminates the impact of variable hyperemic stimulus. Cardiovascular
Ultrasound, 6:44-54, 2008.
- Padilla, J., R.A.
Harris, L.D. Rink, and J.P. Wallace. Characterization
of the brachial artery shear stress following walking exercise.
Vascular Medicine, 13:105-111, 2008.
- Harris, R.A., J.
Padilla K.P. Hanlon, L.D. Rink, J.P. Wallace. Reproducibility
of the Flow-Mediated Dilation Response to Acute Exercise in Overweight
Men, Ultrasound and Medicine and Biology, 16:578–584,
2008.
- Harris, R.A., Padilla,
J., Hanlon, K.P., Rink, L.D., J.P Wallace. The
Flow-Mediated Dilation Response to Acute Exercise in Overweight
Active and Inactive Men, Obesity Research, 16:578–584,
2008.
- Padilla, J., R.A.
Harris, and J.P. Wallace. Can
the measurement of brachial artery flow-mediated dilation be applied
to the acute exercise model? Cardiovascular Ultrasound,
5:45-52, 2007.
- Padilla, J., R.A.
Harris, A.D. Fly, L.D. Rink, and J.P. Wallace. The
effect of acute exercise on endothelial function following a high-fat
meal, European Journal of Applied Physiology, 98:256-262,
2006.
- Padilla, J., R.A.
Harris, A.D. Fly, L.D. Rink, and J.P. Wallace, A
comparison between active and reactive hyperemia-induced brachial
artery vasodilation, Clinical Science, 110:387-392,
2006.
- Harris, R.A., J.
Padilla, and J.P. Wallace. Variability
of flow-mediated dilation measurements with repetitive reactive
hyperemia, Vascular
Medicine, 11:1-6, 2006.
- Harris, RA, J Padilla,
JP Wallace, The Effect of Repetitive Reactive
Hyperemia on Brachial Artery Flow Mediated Dilation Measurements,
Medicine & Science in Sports & Exercise,
37(5) Supplement:S221-S222, 2005
- Padilla, J., R. Harris,
JP Wallace, The Variation of Flow Mediated
Dilation During Morning Hours, Medicine & Science
in Sports & Exercise, 37(5) Supplement:S221, 2005.
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Our most recent
efforts in hypertension have been to compare exercise to physical
activity in the nonpharmalogical treatment of hypertension.
Using ambulatory
blood pressure monitoring (pictured to the right), we are able to
measure blood pressure for 24 hours. We obtain a total of 100 blood
pressures, measuring it every 15 min during the day and every 30
min during sleep.
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Illustrated
above is a typical blood pressure pattern of an adult with hypertension.
The systolic blood pressure is illustrated in red; the diastolic
in yellow; and the normal pressures in green. Normal blood pressure
should be below 140/90 mm Hg during the waking hours and below120/80
mm Hg during the sleeping hours.
With this technology
we have observed the value of the time of day to exercise on the
blood pressure reduction. We have also identified adults with nocturnal
high blood pressure. The tracing above is an adult with normal nocturnal
blood pressure.
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| Saejong
Park
(2006 doctoral graduate)
found that four 10 min sessions of physical activity was more effective
in reducing blood pressure in prehypertension than one 40 min continuous
session of physical activity. These results are original and provocative.
Saejong incorporated Holter monitoring with the ambulatory blood pressures
to investigate the heart rate variability. She found that the changes
in blood pressure were related to changes in sympathetic tone. Her
work has been published in Journal of Hypertension
(article 1
and article
2). |
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Jaume
Padilla,
as a masters student from the University
of Leuven, completed a study in which he measured the ambulatory
blood pressures during life-style physical activity. His subjects
wore the ambulatory monitor while doing yard work and house work.
We found that simple life-style activities such as mowing the lawn,
etc. lowered blood pressure quite effectively in both prehypertension
and hypertension. His work was published in Medicine
and Science in Sports and Exercise. |
Our most recent articles
in exercise and hypertension are:
- Park,
S., L.D. Rink, and J.P. Wallace. Accumulation
of physical activity: blood pressure reduction between 10-min
walking sessions. Journal of Human Hypertension,
22:475-482, 2008.
- Wallace, J.P. and
A. Fly. Lifestyle: Sound Medicine for high blood pressure. ACSM’s
Health & Fitness Journal, 12(2):8-15, 2008.
- Park,
S. D.L. Rink and J.P. Wallace. The
accumulation of physical activity leads to a greater blood pressure
reduction than a single continuous session in prehypertension,
Journal of Hypertension 24:1761-1770, 2006.
- Lehmkuhl,
L.A.A., S. Park, D. Zakutansky, D. Tanner, J. Stager, C.A. Jastremski
and J.P. Wallace, Reproducibility
of postexercise ambulatory blood pressure in Stage I hypertension.
Journal of Human Hypertension 19:589-595, 2005.
- Wallace,
J.P., S. Park, D.W. Zakutansky, L.A.A. Lehmkuhl, and C.A. Jastremski,
Time of day
to monitor ambulatory blood pressure affects the outcome.
Blood Pressure Monitoring 10:43-50, 2005
- Park,
S., C.A. Jastremski, and J.P. Wallace, Time
of day for exercise on blood pressure reduction in dipping and
nondipping hypertension, Journal of Human Hypertension
19:597-605, 2005.
- Padilla,
J., J.P. Wallace, and S. Park, Accumulation
of physical activity reduces blood pressure in pre- and hypertension,
Medicine and Science in Sports and Exercise, 37:1264-1275,
2005.
- Wallace,
J.P., Exercise
in Hypertension: A Clinical Review. Sports Medicine,
33(8):585-598, 2003.
- Wallace,
J.P., P.G. Bogle, B.A. King, J.B.
Krasnoff, and C.A. Jastremski, The magnitude
and duration of ambulatory blood pressure reduction following
acute exercise. Journal of Human Hypertension,13:361-366,
1999.
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Our experience with
exercising adults with diabetes led us to investigate the efficacy
of exercise in treating diabetic neuropathy.
Diabetic neuropathy is
a complication of diabetes where the nerve becomes deficient in
conducting impulses. Neuropathy affects both the sympathetic and
peripheral nerves. Neuropathy of the peripheral nerves compromises
sensation (such as touch) and motor control (such as gait). Neuropathy
of the sympathetic nerves affects anything having to do with autonomic
control. In terms of exercise, autonomic neuropathy affects the
heart rate, blood pressure, blood flow distribution response to
exercise. It also affects the ability to sense angina and hypoglycemia. |
| Several adults with
diabetes who exercised in our programs reported they
could feel their feet again and wanted
to go dancing. Apparently there
was something about the exercise that was changing their neuropathy.
We believed it was the improvement in blood flow associated with
exercise. So, we set out to do a series of studies to investigate
the influence of exercise on blood flow and nerve function.

Franz
Jones
(Master's student 2006) and Don Zakutansky
(doctoral graduate 2006) conducted an experiment which altered blood
flow of the calf and observed the nerve function during the different
levels of blood flow.
The conditions of blood
flow variability are:
- ischemia
- reactive hyperemia
- exercise
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Our most recent publications
are:
- Zakutansky, D.W. K. Kitano, D. M. Koceja, and J.P. Wallace, The effect of blood flow on H-Reflex and motor responses in adults with type 2 diabetes. Journal of Clinical Neurophysiology 26: in press.
- Zakutansky,
D.W., K Kitano, J.P. Wallace, and D.M. Koceja, H-Reflex
and motor responses to acute ischemia in apparently healthy individuals,
Journal of Clinical Neurophysiology 22:210-215, 2005
- Zakutansky,
DW, Kitano, K, Park,SJ, Koceja, DM, Wallace, JP. Sensory
and Motor Responses to Acute Ischemia in Healthy Individuals,
Medicine and Science in Sport and Exercise 36(5) Supplement:S165,
May 2004
- Zakutansky,
D.W. and J.P. Wallace, Relationships among
physical activity, limb blood flow, and autonomic neuropathy tests
in adults with diabetes, Medicine and Science in Sports
and Exercise, 33:S21, 2001
- King, B.A.,
J.P. Wallace, and R.A. Kaplan. The relationship
between VO2max and autonomic neuropathy. Medicine and
Science in Sport and Exercise 29 (Suppl 5): S90, 1997.
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Our obesity research
began in 1992 when Dr.
Wayne Miller joined our research team. Dr. Miller created
the Non-Diet Diet and integrated it into our Weight Loss Clinic,
administered through the Adult Fitness Program.
One of our current research
directions in obesity is directed at the influences of diet and
exercise on endothelial health.
In addition,
we are also working through a behavioral approach to healthy diet
and exercise with Drs. Susan
Middlestadt and Alyce
Fly in Applied Health Sciences. Dr. Middlestadt, a
social behaviorists, is leading the team to find out the success
factors to healthy eating and exercise/physical activity.
Publications from
our obesity research:
- Wallace, J.P., Obesity,
in American College of Sports Medicine: Exercise Management
for Persons with Chronic Diseases and Disabilities, Human
Kinetics Publishers, Champaign, 2002.
- Miller, W.C., T. Swenson,
and J.P. Wallace, Derivation of prediction
equations for residual volume in overweight men and women.
Medicine and Science in Sport and Exercise, 30:322-327,
1998.
- Miller, W.C., M.G.
Niederpruem, J.P. Wallace, and A.K. Lindeman, Dietary
fat, sugar, and fiber predict body fat content. Journal
of the American Dietetic Association 94:612-615, 1994.
- Wallace, J.P., P.K.
Bogle, K. Murray and C.A. Jastremski, Variation
in anthropometric dimensions for estimating upper and lower body
obesity. American Journal of Human Biology 6:699-709,
1994.
- Miller, W.C., J.P.
Wallace, and K. E. Eggert, Predicting max
HR and HR-V02 relationship for exercise prescription in obesity.
Medicine and Science in Sport and Exercise 25:1077-1081,
1993.
- Miller, W.C., J.P.
Wallace, A.K. Lindeman and C. Jastremski, Successful
weight loss in a self-taught, self-administered program.
International Journal of Sports Medicine 14:401-405,
1993.
- Miller, W.C., J.P.
Wallace, K.E. Eggert and A.K. Lindeman, Cardiovascular
risk reduction in self-taught, self-administered weight-loss program
called the Non-Diet Diet. Medicine, Exercise, Nutrition,
and Health 2:218-223, 1993.
- Miller, W.C., A.K.
Lindeman, J.P. Wallace, and M. Niederpruem, Diet
composition, caloric intake, and exercise in relation to body
fatness, American Journal of Clinical Nutrition
52:426 430, 1990.
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MEET
OUR GRADS |
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Greg
Dwyer, Ph.D. FACSM
1986 - 1992
Thesis: Glycosylated hemoglobin and the oxygen
kinetics in individuals with type II diabetes
Current Employment: Associate
Professor, Clinical Exercise Physiology, East Stroudsburg
University, East Stroudsburg, PA
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Galit
Inbar, Ph.D.
1985-1992
Thesis: Hemodynamic determinants of postexercise
hypotension in borderline hypertensive women
Employment: Clinical Exercise Specialist
and Instructor, Wingate Institute, Israel
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Darcy
Sun, Ph.D.
1985-1993
Thesis: Orocecal transit during prolonged
caloric restriction and refeeding
Employment: Director of Cardiac Rehabilitation
and Nutrition Services, Hospital, Macon Georgia
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Mitch
Whaley, Ph.D. FACSM
1988- 1993
Thesis: Maximal aerobic power as a predictor
of cardiac morbidity in adult men and women during long term
follow-up
Employment: Dean College of Applied Sciences
and Technology, Ball
State University.
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Phil
Bogle, Ph.D.
1990-2001
Thesis: Hemodynamic determinants of post
exercise hypotension: An ambulatory study
Employment: Captain Phil Bogle, Ph.D.
Associate Professor
Health, Exercise, & Sport Science
The Citadel
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Lee
Hwa Chen, P.E.D
1993 -2003
Thesis:
Physical activity patterns and its relationship to cardiovascular
risk factors in an adult Taiwanese population
Employment: Assistant Professor, National
College of Physical Education and Sports, Taoyuan, Tiawan.
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Saejong
Park, Ph.D.
2000-2006
Thesis:
The role of physical activity in the treatment of prehypertension:
accumulation vs. continuous exercise.
Employment:
Research Scientist
Korea Institute
of Sport Science
Seoul, Korea
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| Don
Zakutansky, Ph.D.
2000
- 2006
Thesis:
The effects of blood flow on peripheral nerve function in
adults with type 2 diabetes mellitus
Employment:
Lecturer, Gateway College, Wisconsin
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Joanne
Krasnoff, Ph.D.
2002 - 2007
Thesis:
The relationships among health-related fitness measures, physical
activity, and nonalcoholic fatty liver disease
Employment:
Assistant Professor and Associate Director of the Exercise
Physiology and Physical Function Lab for the Division of Endocrinology,
Boston University School of Medicine |
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Ryan
Harris, Ph.D.
2003-2007
Thesis:
The Interaction of TNF-alpha, Interleukin-6, and
acute exercise on endothelial Function
Post-Doc with Russell
Richardson, School
of Medicine, University of California, San Diego
Employment: Assisatant Professor. Medical College of Georgia, Georgia Prevention Institute, Augusta GA |
Jaume
Padilla, Ph.D.
2004-2008
Thesis:
Normalization of brachial artery FMD
Employment:
Postdoctoral Fellow,
Vascular Physiology Laboratory, Department of Biomedical Sciences,
University of Missouri-Columbia |
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Blair Johnson, Ph.D.
2007-2011
Thesis:
The effects of retrograde blood flow and shear stress at rest and during exercise on flow-mediated dilation
Employment: Postdoctoral Fellow,
Exercise Physiology Laboratory, with Michael J. Joyner, M.D., Anestesiology, Mayo Clinic, Rochester MN |
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OUR
CURRENT DOCTORAL CANDIDATES ENGAGING IN THEIR DISSERTATIONS |
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