Effects of Aerobic Exercise in Patients With Pre-diabetes

• 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

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

• Smoking
• Hypertension (B/P > 140/90 or on antihypertensives)
• HDL < 40mg/dl
• 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)