Effects of Aerobic Exercise in Patients With Pre-diabetes
| Status: | Completed |
|---|---|
| Conditions: | Endocrine, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 20 - 70 |
| Updated: | 5/5/2014 |
| Start Date: | March 2010 |
| End Date: | September 2013 |
| Contact: | Annie Lagoy, RN |
| Email: | ann.lagoy@bhs.org |
| Phone: | 413-794-7224 |
The Effect of Controlled Aerobic Exercise on Endothelial Dysfunction and Vascular Reactivity in Patients With Pre-diabetes: A Crossover Pilot Study
It is well known that diabetes and excessive or high blood sugars causes blood vessel and
blood cell damage. It is also possible, then, that people with pre-diabetes may also start
to have blood vessel and blood cell damage as the blood sugars rise from the normal range
into the diabetic range. In addition to looking at potential damage, the question is
whether or not this damage improves with exercise. This study aims to look at blood vessel
and blood cells in three different ways by 1) looking at how the blood vessel responds to
"sheer force" (a blood pressure cuff pumped up and then released after a few minutes). This
is done by ultrasound. 2) By looking at blood tests such as blood sugar, cholesterol, and
inflammation and 3) By looking at certain blood cells in the lab, how long they live and the
number of cells left after a certain number of days, and again, if this improves with
exercise.
blood cell damage. It is also possible, then, that people with pre-diabetes may also start
to have blood vessel and blood cell damage as the blood sugars rise from the normal range
into the diabetic range. In addition to looking at potential damage, the question is
whether or not this damage improves with exercise. This study aims to look at blood vessel
and blood cells in three different ways by 1) looking at how the blood vessel responds to
"sheer force" (a blood pressure cuff pumped up and then released after a few minutes). This
is done by ultrasound. 2) By looking at blood tests such as blood sugar, cholesterol, and
inflammation and 3) By looking at certain blood cells in the lab, how long they live and the
number of cells left after a certain number of days, and again, if this improves with
exercise.
- To refine a non-invasive test for endothelial dysfunction. The investigators will
examine the flow response to sheer-stress induced by the relief of pressure exerted
with a blood pressure cuff on the brachial artery, measuring flow responses with
Doppler. This is a measure of local nitric oxide production from endothelial cells
which is known to be impaired in diabetics, normal in non-diabetics, but unknown in
prediabetics.
- To measure in the same individuals indicators of glucose metabolism abnormalities
including fasting blood glucose, HbA1C, insulin sensitivity by homeostasis model
assessment-estimated insulin resistance (HOMA-IR) and insulin levels.
- To measure Endothelial Progenitor Cell (EPC) count, viability, gene expression of key
genes such as endothelial nitric oxide synthase (eNOS), von-Willebrand's Factor (vWF)
and adhesion molecules such platelet-endothelial cell adhesion molecule-1 (PECAM-1 or
CD31), cadherin such as Vascular-Endothelial cadherin (VE-cadherin)or CD (cell surface
marker)-144, growth factors such as vascular-endothelial growth factor (VEGF)and
Insulin like growth factor (IGF-1)in the EPCs from pre-diabetes subjects pre and post
exercise.
- Correlate the glucose metabolism abnormalities with potential causative factors of
endothelial dysfunction by studying EPC functions such as migration and tube formation
and susceptibility to apoptosis in moderate hyperglycemia. Apoptosis assay will be done
by Flow Cytometry analysis using Annexin V- Propidium-iodide dye.
- Subjects will be randomized to the intervention (structured exercise) or continuation
of their usual life style (non-exercise, sedentary)group.
In both arms of the study, subjects will be encouraged to adhere to the standard dietary
advice that all pre-diabetic patients receive as part of their standards of care,
irrespective of design arm they will be in.
The investigators expect exercise to improve flow-mediated vasodilatation, EPC colony count
and function, along with better key gene expressions noted by Real Time-qualitative
polymerase chain reaction (PCR).
- Assess the effects of the intervention comparing them to the findings in each
individual, in a paired manner.
- After a washout period, individuals will be crossed over to see whether the effects of
the intervention are reversed and to demonstrate that the difference between controls
and intervention subjects was due to the aerobic exercise intervention, and not due to
random differences
examine the flow response to sheer-stress induced by the relief of pressure exerted
with a blood pressure cuff on the brachial artery, measuring flow responses with
Doppler. This is a measure of local nitric oxide production from endothelial cells
which is known to be impaired in diabetics, normal in non-diabetics, but unknown in
prediabetics.
- To measure in the same individuals indicators of glucose metabolism abnormalities
including fasting blood glucose, HbA1C, insulin sensitivity by homeostasis model
assessment-estimated insulin resistance (HOMA-IR) and insulin levels.
- To measure Endothelial Progenitor Cell (EPC) count, viability, gene expression of key
genes such as endothelial nitric oxide synthase (eNOS), von-Willebrand's Factor (vWF)
and adhesion molecules such platelet-endothelial cell adhesion molecule-1 (PECAM-1 or
CD31), cadherin such as Vascular-Endothelial cadherin (VE-cadherin)or CD (cell surface
marker)-144, growth factors such as vascular-endothelial growth factor (VEGF)and
Insulin like growth factor (IGF-1)in the EPCs from pre-diabetes subjects pre and post
exercise.
- Correlate the glucose metabolism abnormalities with potential causative factors of
endothelial dysfunction by studying EPC functions such as migration and tube formation
and susceptibility to apoptosis in moderate hyperglycemia. Apoptosis assay will be done
by Flow Cytometry analysis using Annexin V- Propidium-iodide dye.
- Subjects will be randomized to the intervention (structured exercise) or continuation
of their usual life style (non-exercise, sedentary)group.
In both arms of the study, subjects will be encouraged to adhere to the standard dietary
advice that all pre-diabetic patients receive as part of their standards of care,
irrespective of design arm they will be in.
The investigators expect exercise to improve flow-mediated vasodilatation, EPC colony count
and function, along with better key gene expressions noted by Real Time-qualitative
polymerase chain reaction (PCR).
- Assess the effects of the intervention comparing them to the findings in each
individual, in a paired manner.
- After a washout period, individuals will be crossed over to see whether the effects of
the intervention are reversed and to demonstrate that the difference between controls
and intervention subjects was due to the aerobic exercise intervention, and not due to
random differences
Inclusion Criteria:
- Prediabetic
- Impaired fasting glucose (100-125mg/dl)
- Impaired glucose tolerance (2' post between 140-199mg/dl)
- HbA1C 5.7-6.4 mg/d (inclusive)
- Exercise Naive
- BMI between 20-39.9
- Nutritional Counseling prior to participation with CDE/RD
- Willing to wear activity monitor
- Willing to keep a dietary log
Exclusion Criteria:
- Pace maker or other implanted device that might have interference with Tanita scale
- Any contraindication to moderate exercise
- Previous coronary disease or cerebrovascular event active or clinically significant
coronary vascular disease, or peripheral vascular disease
- Diabetes
- Uncontrolled hypertension (SBP > 140 or DBP > 90 on 3 separate occasions) ACE's or
ARB's
- Premature familial CAD (Father < 55years____ Mother <65years)
- HDL < 40mg/dl
- Triglycerides >400mg/dl
- Any new lipid lowering medication started in the past 6 months
- Framingham Risk Score two or more
1. Smoking
2. Hypertension (B/P > 140/90 or on antihypertensives)
3. HDL < 40mg/dl
4. Age men >45years or women >55years
- Low hematocrit ( or hemoglobinopathies that may impair exercise tolerance) or
abnormal CBC
- Uncontrolled hypo/hyperthyroidism
- Active smoking
- Liver disease ( alt or AST> 2.5's UNL)
- Moderate or Severe Kidney disease, current or history
- Pancreatitis, current or history
- Any medication started in the last 3 months
- Active non healing wounds
- Recent Surgery in the last 3 months
- Anti-inflammatory disease, current or history
- Regular use of anti-inflammatory drugs
- CA
- Alcoholism
- Women who are pregnant or intending to become pregnant
- Oral or Injectable antidiabetic medication
- Post menopausal women on hormone replacement
- Any steroid medication (oral, inhaled, injected or nasal)
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