Effects of Aerobic Exercise in Patients With Pre-diabetes
Condition: Prediabetes
MeSH terms: Prediabetic State; Glucose Intolerance
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      -  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
    

Intervention name(s): Exercise; Without exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 150 minutes of moderate exercise per week; Pre-study activity level (i.e. no exercise)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: prediabetes; EPC's; vascular reactivity