Clinical Exercise Physiology
Clinical Research

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

2012-13 Clinical Exercise Physiology Lab Team

Micah Enyart, Dr. Barbara Campaigne, Chad Wiggins, Sylvanna Bielko, Saurabh Thosar, Dr. Janet P. Wallace, and Dr. Kieren Mather.
Back row: Anna Gabbard and Ning Ding.

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.


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.

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. 


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.


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.


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.



Our recent publications in endothelial function include:

  1. Thosar, S.S., B.D. Johnson, J. Johnston, and J.P. Wallace. Sitting and endothelial dysfunction: the role of shear stress.  Medical Science Monitor, 18:RA173-180, 2012
  2. Johnson, Blair, D., Kieren J. Mather, Sean C. Newcomer, Timothy D. Mickleborough, and Janet P. Wallace. Alterations of brachial artery shear rate profiles during lower body exercise influences post-exercise flow-mediated dilation: possible role of oxidative stress, Cardiovascular Ultrasound, 10:34, 2012.
  3. 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.
  4. Johnson, B.D. and J. P. Wallace. A comparison of postexercise shear rate patterns following different intensities and durations of running in healthy men. Clinical Physiology and Functional Imaging, 32:234-240, 2012.
  5. 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
  6. 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).
  7. 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.
  8. 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
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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
  19. 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.



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.


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.

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).

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:

  1. 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.
  2. Wallace, J.P. and A. Fly. Lifestyle: Sound Medicine for high blood pressure. ACSM’s Health & Fitness Journal, 12(2):8-15, 2008.
  3. 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.
  4. 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.
  5. 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
  6. 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.
  7. 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.
  8. Wallace, J.P., Exercise in Hypertension: A Clinical Review. Sports Medicine, 33(8):585-598, 2003.
  9. 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.


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

Our most recent publications are:

  1. 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.
  2. 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
  3. 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
  4. 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
  5. 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.














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:

  1. Wallace, J.P., Obesity, in American College of Sports Medicine: Exercise Management for Persons with Chronic Diseases and Disabilities, Human Kinetics Publishers, Champaign, 2002.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.


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

Galit Inbar, Ph.D.

Thesis: Hemodynamic determinants of postexercise hypotension in borderline hypertensive women

Employment: Clinical Exercise Specialist and Instructor, Wingate Institute, Israel

Darcy Sun, Ph.D.

Thesis: Orocecal transit during prolonged caloric restriction and refeeding

Employment: Director of Cardiac Rehabilitation and Nutrition Services, Hospital, Macon Georgia

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.

Phil Bogle, Ph.D.

Thesis: Hemodynamic determinants of post exercise hypotension: An ambulatory study

Employment: Captain Phil Bogle, Ph.D.
Associate Professor
Health, Exercise, & Sport Science
The Citadel

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.

Saejong Park, Ph.D.


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

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

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

Ryan Harris, Ph.D.


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.


Thesis: Normalization of brachial artery FMD

Employment: Postdoctoral Fellow, Vascular Physiology Laboratory, Department of Biomedical Sciences, University of Missouri-Columbia

Blair Johnson, Ph.D.


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


Contact Us:
Program Coordinator Janet P. Wallace, Ph.D., FACSM
Graduate Advisor John Raglin, Ph.D.
Status of your Application Debbie Szemcsak
To Obtain an Application
Dean of Academic Affairs Kathy Gilbert, Ph.D.

Clinical Exercise Physiology Laboratory
HPER 070
Bloomington, IN 47405

office: (812) 855-7556
fax: (812) 855-3193

Page Updated: 10-Dec-2012
Webmasters: Janet P. Wallace
Mail to:
Copyright: Indiana University