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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prediabetes with exercise | Other | 150 minutes of moderate exercise per week |
|
| Prediabetes without exercise | Other | Pre-study activity level (i.e. no exercise) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise | Behavioral | 150 minutes of moderate exercise per week |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Measures of Endothelial Function by studying number, function and gene expression of endothelial progenitor cells (identified as CD34+ cells) | A. Number of viable CD34 +ve cells at Day-0 and viability assay. B. Colony Formation count assay at Day-5, pre and post exercise. C. We will test CD34+ cell migration, adhesion and tube formation properties. D. Gene expression in CD34+ cells of critical endothelial function and inflammatory genes will be measured: eNOS, vWF and PECAM1, VE-cadherin, VEGF-A, Superoxide dismutase (SOD)-1, 2 and 3, Catalase, Interleukin (IL)-6, Tumor Necrosis Factor (TNF alpha), P53, P21, PUMA, Bcl2 [Apoptosis genes] will also be noted | 16 weeks per patient |
| Measure | Description | Time Frame |
|---|---|---|
| Measures of Vacular Reactivity | A) Measure Brachial reactivity through shear-stress using flow mediated dilatation (FMD) B). Measure Arterial Stiffness measure pre and post exercise. C) Measure Carotid Intima Media Thickness will be measured at each time point | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Measures of Insulin Sensitivity by measuring inflammatory molecules as a surrogate of insulin resistance | We will measure: A. plasma measurements of cytokines, including C - reactive protein, E-selectin, IL-6, IL-10, thrombin, leptin, adiponectin, fasting glucose, fasting insulin and fasting lipid profile from subjects are expected to reflect endothelial inflammation. B. Insulin sensitivity will be evaluated at baseline and weeks 6, 10 and16 using the HOMA ratio, calculated from individual serum measures (fasting glucose* insulin/405) C.Adiposity will be measured at baseline and at weeks 6, 10, and 16 using the Tanita Body Composition Analyzer scale, measured as percentage body fat D. Resting energy expenditure as measures of indirect calorimetry for basal metabolic rate measures (BMR). |
Inclusion Criteria:
Prediabetic
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
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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| Name | Affiliation | Role |
|---|---|---|
| Sabyasachi Sen, MD, PhD | Baystate Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
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| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| Without exercise |
| Behavioral |
Pre-study activity level (i.e. no exercise) |
|
| 16 weeks |
| D004700 | Endocrine System Diseases |