Prescribing exercise for diabetes prevention

1. Clinical blood pressure, recorded using a programmable automated device (BP-TRU™ 100 model, Vancouver, BC)
2. Blood glucose, lipid profiles, CRP and markers of RAS function: fasting blood glucose will be measured in the institutional setting using laboratory assays. In the rural setting, patients will use a remote monitoring glucometer (Bluetooth® enabled) as well as scheduled laboratory assays. Lipid profiles and CRP will be assessed using laboratory assays. Plasma catecholamines will be assessed by high pressure liquid chromatography whereas vasopressin, angiotensin and cortisol will be determined by radioimmunoassay approaches.
3. Predicted V02 max: subjects will perform a modified self-selected STEP™ test. Based on values of subject's height, weight, resting heart rate, training heart rate, and performance on the STEP™ test, V02 max values will be calculated.
4. Body composition, body mass index (BMI - kg/m^2), waist circumference

All measured at baseline, 3, 6, 9 and 12 months.

1. 3D ultrasound measurement of carotid artery: patients will undergo a 3D ultrasound exam to assess the extent of their carotid atheromatous disease
2. Behavioural measures: surveys to examine changes in behaviour change with exercise interventions and quality of life, i.e., stage of change, self efficacy, decisional balance, SF-36
3. Physiological measures:
3.1. Cardiac function: standard echocardiographic approaches using B-mode and M-mode echo Doppler imaging will be performed by a certified echocardiographic technologist. Image location and gain settings will be adjusted to yield optimal definition of endocardial and epicardial borders. Chamber and wall dimensions will be measured according to the standard methods of the American Society of Echocardiography and left ventricular (LV) fractional shortening will be calculated from the difference between systolic and diastolic cavity dimensions over 3 cardiac cycles at end diastole taken at the QRS peak. LVM will be calculated according to the method of Devereux et. al. and normalised to body surface area (BSA). Left ventricular diastolic filling will be assessed in the left lateral decubitus position (supine) or sitting (upright) and data manually traced and digitised from 5 cardiac cycles in each subject. Pulsed Doppler transmitral flow velocities will be taken from the apical 4-chamber view between the tips of the mitral valve leaflets. Doppler data will be manually traced and digitised in each subject. Measures of peak early flow velocity (E), atrial flow velocity (A), isovolumic relaxation time (IVRT) and early deceleration time (DT) will be recorded at a sweep speed of 50 or 100mm/s. Intimal-media thickness of the right common carotid artery will be assessed with longitudinal B-mode images of the carotid artery in the patient's supine position with the head turned 45 degrees away from the side examined at a straight portion of the artery 1 - 2 cm proximal to the bifurcation.
3.2. Vascular properties: major conduit vessels will be examined because these provide the major buffering capacity for systolic pressure and they provide enhanced spatial resolution for analysis. Using B-mode echo Doppler imaging and the EchoPak software in the GE/Vingmed Ultrasound machines (System FiVe and Vivid I) we will measure the wall thickness (anterior and posterior wall) and cross-sectional diameter of each arterial segment at systole and again at end diastole. Electrocardiogram (ECG) markers will provide cues about the cardiac cycle phase. Measures of all variables will be made from three separate cardiac cycles in carotid, femoral and aortic vessels taken at end expiration. This procedure should take approximately 45 minutes, which includes setup time and verification of the data.
3.3. Muscle sympathetic nerve activity: microneurographic sympathetic activation will be obtained from the common peroneal nerve. A 200 µm-diameter, 35 mm long tungsten microelectrode that tapered to an uninsulated 1- to 5-µm tip is inserted transcutaneously into the perineal nerve just posterior to the fibular head. A reference electrode is positioned subcutaneously 1 - 3 cm from the recording site. Neuronal activity is amplified 1,000 times by a pre-amplifier and 50 - 100 times by a variable gain isolated amplifier. The signal is band-pass filtered with a bandwidth of 700 - 2,000 Hz and then rectified and integrated to obtain a mean voltage neurogram (0.1 sec time constant). A muscle sympathetic nerve activity (MSNA) site is confirmed by the characteristic pulse-synchronous burst pattern that does not produce skin paresthesias and that increases in frequency during a voluntary apnea but not during arousal to a loud noise.
3.4. Lower body negative pressure: the participant's lower body will be sealed inside an air-tight box at the hips. A small vacuum can be created in this box that mimics the effect of postural changes on the cardiovascular system. Levels of suction up to -40 mmHg will be used; this simulates levels of cardiovascular stress that are equivalent to the seated position.
3.5. Cardiovascular reactivity: the Stroop Test - subjects are asked to identify the colour of the text ignoring the semantic meaning of the word. Presentation of slide rate is increased over time to create an increasing stress level. Blood pressure, heart rate and MSNA will be measured as indices of the stress response.
3.6. Forearm endothelial function: using B-mode echo Doppler ultrasound we will make continuous measures of brachial artery diameters for 3 minutes following the release of a 5 - 10 minute period of forearm circulatory occlusion. This test is used as an index of endothelial function as the brachial artery dilation is related to shear stress. To test the effect of endothelial dysfunction the test will also be performed before and after the sublingual administration of 0.4 mg nitroglycerine. The nitroglycerine acts as a nitric oxide donor and will enhance both diameter and compliance responses under conditions where inadequate endothelial-derived nitric oxide is produced.
3.7. Continuous blood pressure: a finger cuff device (Finometer) will be used to measure blood pressure continuously. Similarly, a pulse oximeter will be placed around a toe in order to detect flow oscillations at that site. The finger cuff may feel a little tight and the finger may turn blue while in operation. However, these sensations go away immediately when the machine is turned off.

All measured at baseline, 3, 6, 9 and 12 months.