Cardiovascular adaptations to exercise training in postmenopausal women with type 2 diabetes mellitus

A total of 28 postmenopausal women with clinically documented DM-2, free from diabetic complications, were screened for underlying coronary artery disease with resting and maximal exercise electrocardiograms. Exclusion criteria for this investigation included: evidence of ischemic heart disease by history or positive resting or exercise electrocardiogram; angina or any other cardiac symptoms potentially limiting exercise capacity; and/or presence of musculoskeletal or peripheral vascular abnormalities that would limit exercise capacity. Written informed consent was obtained from all subjects prior to the investigation and the Research Ethics Review Board within the Faculty of Medicine at the University of Alberta approved the study protocol.

Prior to exercise training, subjects were evaluated over the course of two separate visits. Initially, participants reported to the University of Alberta Hospital, Division of Cardiology for a history and physical examination as well as a resting and exercise electrocardiogram. A graded exercise test was performed on an electronically braked cycle ergometer to determine ventilatory threshold and cardiorespiratory fitness. On the second visit, subjects reported to the Metabolic Unit following an overnight fast for blood work, applanation tonometry and resting echocardiograms. A period of at least 48 hours separated the two visits, to allow for complete recovery of the acute effects of the exercise test. Following baseline testing, participants were assigned to either control (CT) or exercise training (ET) groups. The data reported here are a combination of pilot data collected in 10 subjects and a second study in which 18 patients were randomly distributed into two groups (exercise or control). Of the 28 originally screened patients, four women were initially excluded due to either positive stress test or inability to perform the exercise training requirements of the investigation. Therefore 24 women were included in the initial investigation (ET = 17, CT = 7). Six women were excluded from the analysis due to poor adherence to the exercise intervention. Adherence was determined by attendance and completion of 80% of the prescribed exercise training. Therefore data from18 women were included in the final analysis of this investigation (ET = 11; CT = 7). The remaining eleven participants in the ET group completed 92 ± 3% of the exercise sessions. Individuals in this investigation were treated for diabetes through diet and exercise (n = 5) or oral hypoglycemic agents (n = 13), while no participants were on insulin therapy.

Oxygen consumption, carbon dioxide production and minute ventilation were sampled every five seconds at rest and during exercise using a Parvo Medics TrueMax 2400 Metabolic Cart (Parvo Medics, East Sandy, UT). The graded exercise test was performed on a cycle ergometer. The stress test began at an exercise intensity of 30 watts and increased by 20 watts every two minutes. Heart rate (electrocardiogram), blood pressure (auscultation) and ratings of perceived exertion were recorded at the end of every two-minute stage. Peak rate of oxygen consumption () was determined from the average rate of oxygen consumption over the final 60 s of the exercise test. The heart rate response to graded exercise was used to prescribe exercise intensity during the exercise intervention.

Resting measurements of vascular function were performed in the morning with the participants fasted, lying supine in a dimly lit room, having refrained from vasoactive medications for a period of 48 hours prior to testing. Arterial compliance was assessed using computerized arterial pulse waveform analysis by a trained investigator. This technique involves 30-s recordings of signal-averaged arterial pulse waves by applanation tonometry using a surface residing pressure transducer on the radial artery (Hypertension Diagnostics Inc., Eagan MN). A single investigator performed all measurements of arterial compliance. Two components of arterial compliance were calculated based on a modified Windkessel model of circulation: capacitive compliance (large artery), and oscillatory (or reflective) compliance [12]. This technique has been validated previously [12].

Imaging of the LV was performed as previously described [5, 13]. In brief, all images were captured using a commercially available ultrasound instrument (Hewlett Packard, Sonos 5500) with a 3.5 MHz transducer by a trained technician. The same technician acquired and analaysed pre and post-intervention images for each participant. Subjects were required to lie quietly for a period of 5–10 minutes, in a dimly lit quiet room prior to imaging. Two-dimensional transthoracic images of the LV were obtained from the parasternal short-axis view at the level of the mid-papillary muscles according to American Society of Echocardiography guidelines [13]. LV diastolic filling dynamics were assessed using pulsed-wave Doppler analysis of transmitral and pulmonary venous flow patterns recorded in the apical four-chamber view [5]. All echocardiographic images were averaged over three cardiac cycles.

Blood was drawn in the fasted state prior to ultrasound imaging. The following haematological parameters were determined using common laboratory procedures [14‐17]: glucose, insulin, glycosylated hemoglobin (HbA_1c), total cholesterol, high and density low lipoproteins and triglycerides. Insulin was measured using a Roche Diagnostics Elecsys 2010 System using the sandwich principle [14]. Plasma lipids [15‐17], glucose and HbA_1c were determined on a Synchron LX20 analyzer (Beckman Coulter, Fullerton CA). The homeostasis model assessment (HOMA index) was used as an estimate of insulin sensitivity [18].

The 10-week exercise intervention consisted of three supervised exercise sessions per week and included a combination of aerobic and resistance training. The aerobic component of the exercise program was performed on a cycle ergometer for 30–55 minutes at intensities between 65 and 75% of heart rate reserve. The intensity and duration of the aerobic component of the exercise intervention increased weekly so that each participant was performing 55 minutes of aerobic exercise at ~75% of heart rate reserve in the final week of the training program. Resistance training consisted of three sets of 10–15 repetitions at a resistance between 50 and 65% of one-repetition maximum in large muscle groups, using the following exercises: chest press, latissimus dorsi pull down, shoulder press, biceps curls, leg press, leg curl and leg extension. The resistance applied to each apparatus was increased each week so that each participant was performing three sets of 10 repetitions at 65–70% of the original one-repetition maximum. Control subjects were asked to continue their previous physical activity patterns throughout the 10-week intervention period.

All statistical analyses were performed using SPSS software (Version 11.0, SPSS, Chicago, IL). A repeated measures ANOVA was used to compare the effects of an exercise and control condition on LV filling dynamics, arterial compliance and risk factors for CVD. Tukey post-hoc analyses were performed to determine group differences. A p value of <0.05 was considered statistically significant.

Baseline characteristics of both groups are provided in Table 1. At baseline, there were no significant differences in conventional risk factors for CVD, such as age, body mass index, systolic blood pressure, lipid profile, hormone replacement therapy or fasting insulin or glucose levels between the two groups. No differences in peak exercise variables were observed between the ET and CT groups at baseline. The average respiratory exchange ratio values at peak exercise in both groups did not exceed 1.10, however they were not significantly different between the groups (1.06 ± 0.04 vs 1.05 ± 0.05 in the ET and CT groups respectively).

Resting hemodynamics prior to and following the exercise intervention are provided in Table 2. After 10 weeks of exercise training, increased by approximately 15% (21.3 ± 3.3 to 24.5± 4.2 ml·kg^-1·min^-1; p < 0.05) in the ET group. Maximal heart rate and respiratory exchange ratio values at follow-up testing were similar to baseline values, suggesting similar effort for both tests. Cardiorespiratory fitness was not assessed in the CT group during follow-up testing.

Fasting blood glucose, insulin and lipid profile before and after the 10-week intervention period are presented in Table 1. Hematological variables were not significantly different in either group following the intervention time period. The HOMA index of insulin sensitivity decreased by ~17% in the ET while it did not change in CT. These changes in the HOMA index however, did not reach statistical significance.

LV filling dynamics, estimated from Doppler-derived transmitral and pulmonary venous flow profiles, were not significantly different following the intervention time period in either group (Table 2). In the ET group, large artery compliance increased by ~16% in response to exercise training (p < 0.05), while small artery compliance remained unchanged. Large and small artery compliance were unchanged in the CT group.