Background
There is limited information regarding the role of left ventricular (LV) twist and the effect of exercise in type 2 diabetes (T2D). The aim of this study was to compare LV twist parameters in patients with T2D versus healthy control subjects and the effects of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on LV twist in patients with T2D with diastolic dysfunction.
Methods
This study, which included both prospective and retrospective components, included 47 patients with T2D and diastolic dysfunction and 37 healthy individuals. Patients with T2D were randomized to HIIE (4 × 4 min at 90%–95% of maximal heart rate, three times a week, 120 min/wk; n = 24) or MIE (210 min/wk; n = 23) for 12 weeks and examined with echocardiography (LV twist by speckle-tracking method) at baseline and posttest. The control subjects received no intervention and were matched according to age, gender, and body mass index to those completing the intervention.
Results
In total, 37 subjects completed 12 weeks of MIE ( n = 17) or HIIE ( n = 20). LV peak untwist rate (UTR) was similar in patients with T2D and control subjects ( P ˃ .05). At baseline, LV peak UTR, relative to total diastolic period, occurred 5.8 percentage points later in patients with T2D compared with control subjects ( P = .004). Time to peak UTR was shortened by 6.5 percentage points ( P = .002) and 7.7 percentage points ( P < .001) after MIE and HIIE, respectively. Time to peak UTR was similar to that in control subjects after exercise interventions.
Conclusions
In patients with T2D and diastolic dysfunction, LV peak UTR was similar, but time to peak LV UTR was delayed compared with control subjects. Twelve weeks of endurance exercise normalized the timing of UTR.
Type 2 diabetes (T2D) is associated with cardiomyopathy, which may lead to heart failure. Early diabetic cardiomyopathy is often characterized by diastolic dysfunction (DD), which has been detected in about 50% of asymptomatic and normotensive subjects with well-controlled T2D.
Although not commonly evaluated, a fundamental component in normal diastolic function is left ventricular (LV) untwist, which contributes to LV relaxation and suction. LV twist and untwist are the wringing and unwringing motion of the left ventricle around the long axis of the ventricle. The sequence of twisting and untwisting events establishes the peak early diastolic blood flow velocity across the mitral valve. Twist during systole contributes with storage of energy, and the subsequent recoil releases the restoring forces, which contributes to LV diastolic relaxation and early filling. Assessment of LV untwisting has thus been introduced as a promising index in the evaluation of early diastolic function. However, there is limited information regarding the role of LV twist in T2D.
Exercise training is a cornerstone in T2D management to reduce cardiovascular disease and mortality, and several studies have shown that high-intensity interval exercise (HIIE) is superior to moderate-intensity exercise (MIE) according to current exercise guidelines in reducing cardiovascular risk factors. We recently reported that HIIE is superior to MIE in improving diastolic function measured by peak mitral annular early tissue Doppler velocity (e′) in patients with T2D and DD. However, to our knowledge no study has investigated the effects of exercise on LV untwist and untwist rate (UTR) in patients with T2D and DD. Thus, the aims of this study were to (1) determine the effects of HIIE and MIE on LV untwist and UTR in patients with T2D (duration < 10 years) and DD and (2) compare these with healthy individuals with no exercise intervention.
Methods
Study Population
A total of 84 subjects, 47 patients with T2D and DD and 37 healthy individuals, were enrolled in the study. The T2D group was recruited prospectively, and the control subjects were recruited retrospectively.
The T2D study population studied has been described previously and was recruited through a local newspaper and from the outpatient population at St Olav’s Hospital, Trondheim, Norway (August 2010 to March 2013). Inclusion criteria for the individuals with T2D included age 20 to 65 years, diagnosis with T2D within 10 years, no use of insulin, and reduced diastolic function, defined as e′ < 8 cm/sec, at baseline testing. Exclusion criteria included overt cardiovascular disease, atrial fibrillation or other significant cardiac arrhythmia, untreated hypertension, diabetic retinopathy or neuropathy, albuminuria, LV ejection fraction (EF) < 40%, body mass index (BMI) > 35 kg/m 2 , ischemia on exercise stress echocardiography on a stationary bicycle, pregnancy, inability to exercise, drug or alcohol abuse, and physical activity level above minimum guidelines for T2D.
The T2D study participants were stratified according to gender and randomized to either HIIE ( n = 24) or MIE ( n = 23) ( Figure 1 ). The Unit of Applied Clinical Research at the Norwegian University of Science and Technology performed the randomization procedures. The trial ( ClinicalTrials.gov identifier NCT01206725 ) was approved by the Regional Committee for Medical and Health Research Ethics of Central Norway in September 2010.
The healthy control subjects ( n = 37) were recruited from the Nord-Trøndelag Health Study database, consisting of 1,266 complete echocardiograms from healthy individuals free of known cardiac disease, diabetes, and hypertension. They were matched, to the extent possible, according to age, gender, and BMI with the final 37 participants with T2D performing posttest measurements. Age and BMI differences between the T2D group and control group of 5 years and 5 kg/m 2 , respectively, were accepted. The control group had no exercise intervention. Informed consent was obtained from all participants, and all were insured.
Outcome Measures
The primary outcome measure was LV peak UTR. Secondary outcome measures were time to peak LV UTR, peak LV twist rate, and peak LV twist.
Intervention and Exercise Training Protocols
T2D Group
The MIE group performed home-based exercise training for 12 weeks in accordance with guidelines from the Norwegian Diabetes Association (2005), recommending MIE for 210 min/wk (exercise bouts ≥10 min in duration), similar to the guidelines of the International Diabetes Federation. At 4 and 8 weeks of the intervention period, the MIE group was contacted by phone or e-mail to motivate to continue with MIE as prescribed.
The HIIE group performed supervised exercise training by walking or jogging on an inclined treadmill three times a week for 12 weeks (120 min/wk). Following 10 min of warmup at 70% of maximal heart rate, the HIIE group performed 4-min work bouts four times at 90% to 95% of maximal heart rate with 3-min recovery periods between work bouts at 70% of maximal heart rate and 5 min of cool-down (altogether 40 min). During the HIIE sessions, heart rate monitors (Polar RS 400; Polar Electro, Kempele, Finland) were used to ensure that the required exercise intensity was achieved and maintained. The individuals in the MIE and HIIE groups recorded daily physical activity.
Echocardiographic Recordings
Echocardiographic examinations (Vivid 7 scanner, phased-array [M4S and M3S transducers]; GE Vingmed Ultrasound AS, Horten, Norway) were performed at baseline and 12 weeks posttest for the MIE and HIIE groups. The control subjects were examined only once. A detailed description of the echocardiographic recordings has previously been published.
The same operator (C.B.I.) performed the echocardiographic recordings at both time points for the T2D population and the same operator (H.D.) for the healthy control group. The images were obtained in parasternal and three standard apical views (four chamber, two chamber, and apical long-axis), both in B-mode and with color tissue Doppler imaging, and three loops were acquired for each image. The images were digitally stored on a hard disk for offline analysis. All recordings were performed with the individuals in the left lateral supine position during breath holds at end-expiration. Basal and apical LV short-axis levels were recorded for the analysis of twist and standardized to two anatomic landmarks. The basal level was recorded from the parasternal position, using the mitral valve leaflet location in the middle of the LV cavity as the landmark. The apical level was recorded more distally toward the apex, just proximal to the level with luminal closure at end-systole. All loops were recorded with the LV cross-sections as circular as possible. To optimize image quality, the sector depth and width were adjusted in each subject, resulting in a mean frame rate of 69 ± 13 frames/sec (range, 51–113 frames/sec). To determine the timing of cardiac events, tissue Doppler velocity curves with the sample volume at the basal septum were conducted immediately before the acquisition of the short-axis images, to minimize differences in heart rate. Aortic valve closure (AVC) was set at the end of the negative spike after ejection.
Echocardiographic Analyses
Offline data analyses were performed using commercially available two-dimensional strain software (EchoPAC PC version 112; GE Medical Systems, Milwaukee, WI). All analyses were performed blinded to exercise group allocation as well as baseline and posttest. Analyses of conventional echocardiographic diastolic measures were performed as previously described.
The analyses of the twist parameters have been described previously. To analyze twist parameters, one cardiac cycle from the basal and apical short-axis data set with a well-defined endocardial border during late systole was selected for analyses. Regions of interest of the left ventricle were adjusted to include most of the myocardium, but not the pericardium. The endocardial borders of the apical and basal short-axis plane at end-systole were manually traced and subsequently tracked by the software. When the software or the observer signaled poor tracking quality, the observer readjusted the region of interest until acceptable tracking was obtained. If nonadjustable, segments with poor tracking were discarded. For the twist analysis, default spatial and temporal smoothing was used.
The twist variables are presented in Tables 1 to 3 . In addition, the timing of AVC and the length of the cardiac cycle (i.e., the time interval between the R waves on the electrocardiogram) were measured. Curves of basal and apical LV rotation, twist, and twist rates were automatically generated by the software. LV twist was calculated (Excel; Microsoft Corporation, Redmond, WA) as apical LV rotation relative to the base. Counterclockwise rotation as viewed from the LV apex was expressed as a positive value and clockwise rotation as a negative value ( Figure 2 ). Peak UTR was defined as the first negative peak after AVC.
| Variable | Control | T2D, baseline | MIE, baseline | MIE, posttest | HIIE, baseline | HIIE, posttest | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | n | Mean ± SD | |
| LV base | ||||||||||||
| Heart rate basal (beats/min) | 37 | 66 ± 11.3 | 36 | 71.2 ± 9.8 | 17 | 72.9 ± 10.3 | 15 | 72.1 ± 9.1 | 19 | 69.8 ± 9.3 | 19 | 65.2 ± 9.3 |
| Peak basal rotation | 37 | −5.2 ± 2.7 | 36 | −5.5 ± 3.2 | 17 | −5.3 ± 3.8 | 15 | −4.3 ± 2.5 | 19 | −5.6 ± 2.7 | 19 | −4.2 ± 2.2 |
| Basal TR (deg/sec) | 37 | −42.1 ± 17.2 | 36 | −54.2 ± 26.1 | 17 | −54.4 ± 24.8 | 15 | −54 ± 23.1 | 19 | −54.1 ± 27.9 | 19 | −45.4 ± 17.8 |
| Basal UTR (deg/sec) | 37 | 52.3 ± 16.4 | 36 | 57.2 ± 25.6 | 17 | 60.9 ± 29.6 | 15 | 52.3 ± 28.4 | 19 | 54 ± 21.8 | 19 | 47.4 ± 23.6 |
| Time to peak basal UTR (% of diastole) | 37 | 8 ± 4.7 | 35 | 13.9 ± 7.2 | 16 | 14.4 ± 6 | 15 | 9.4 ± 4.8 | 19 | 13.5 ± 8.3 | 19 | 8.4 ± 4.6 |
| LV apex | ||||||||||||
| Heart rate apical (beats/min) | 37 | 64.8 ± 10.5 | 36 | 70.2 ± 9.6 | 17 | 73.2 ± 10.2 | 15 | 71.7 ± 9.7 | 19 | 67.5 ± 8.4 | 19 | 65.7 ± 9.1 |
| Peak apical rotation | 37 | 8.5 ± 3.5 | 36 | 8.5 ± 3.6 | 17 | 8.9 ± 3.7 | 15 | 8.2 ± 4.2 | 19 | 8 ± 3.6 | 19 | 9.2 ± 4 |
| Apical TR (deg/sec) | 37 | 40.8 ± 11.9 | 36 | 49.3 ± 24.1 | 17 | 52 ± 29.6 | 15 | 52.9 ± 24.3 | 19 | 46.9 ± 18.3 | 19 | 45.7 ± 23.4 |
| Apical UTR (deg/sec) | 37 | −61.4 ± 18.5 | 36 | −59.8 ± 25.3 | 17 | −56.9 ± 28.1 | 15 | −76 ± 27.1 | 19 | −62.5 ± 23 | 19 | −61.9 ± 23.4 |
| Time to peak apical UTR (% of diastole) | 37 | 8.8 ± 6.3 | 35 | 19.4 ± 9.4 | 16 | 21 ± 9.2 | 16 | 9.7 ± 8.5 | 19 | 18.1 ± 9.6 | 19 | 10.2 ± 5 |
| LV twist | ||||||||||||
| Peak twist | 37 | 13.1 ± 3.6 | 36 | 12.3 ± 5.1 | 17 | 12.5 ± 5.7 | 15 | 10.5 ± 4.7 | 19 | 12.2 ± 4.7 | 19 | 11.3 ± 4.2 |
| Peak TR (deg/sec) | 37 | 65.4 ± 20.9 | 36 | 72.7 ± 31.8 | 17 | 72 ± 33.8 | 15 | 67.9 ± 26.2 | 19 | 73.3 ± 30.9 | 19 | 70.1 ± 29.4 |
| Peak UTR (deg/sec) | 37 | −92.8 ± 23.4 | 36 | −83.2 ± 33.4 | 17 | −86.5 ± 34.9 | 15 | −89.4 ± 33.8 | 19 | −80.2 ± 32.6 | 19 | −77.5 ± 25.1 |
| Time to peak UTR (% of diastole) | 37 | 10.5 ± 7.4 | 35 | 16.3 ± 8.9 | 16 | 16.1 ± 9 | 15 | 10.2 ± 7.7 | 19 | 16.5 ± 9 | 19 | 8.8 ± 4.1 |
| Variable | T2D vs control, baseline | MIE vs control, posttest | HIIE vs control, posttest | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 95% CI | 95% CI | 95% CI | ||||||||||
| Estimate | Lower | Upper | P | Estimate | Lower | Upper | P | Estimate | Lower | Upper | P | |
| LV base | ||||||||||||
| Heart rate basal (beats/min) | 5.2 | 0.3 | 10.2 | .04 | 6.1 | 0.0 | 12.2 | .05 | −0.8 | −6.5 | 4.9 | .78 |
| Peak basal rotation | −0.2 | −1.6 | 1.2 | .74 | 0.9 | −0.6 | 2.5 | .23 | 1.0 | −0.3 | 2.3 | .13 |
| Basal TR (deg/sec) | −12.1 | −22.5 | −1.7 | .02 | −11.9 | −25.6 | 1.9 | .09 | −3.3 | −13.4 | 6.7 | .51 |
| Basal UTR (deg/sec) | 5.0 | −5.1 | 15.1 | .33 | 0.0 | −16.4 | 16.4 | .99 | −4.9 | −17.3 | 7.5 | .43 |
| Time to peak basal UTR (% of diastole) | 5.9 | 3.0 | 8.9 | <.001 | 1.5 | −1.6 | 4.5 | .33 | 0.5 | −2.2 | 3.1 | .72 |
| LV apex | ||||||||||||
| Heart rate apical (beats/min) | 5.4 | 0.7 | 10.1 | .03 | 6.9 | 0.7 | 13.2 | .03 | 1.0 | −4.5 | 6.4 | .73 |
| Peak apical rotation | −0.1 | −1.7 | 1.6 | .94 | −0.3 | −2.9 | 2.2 | .79 | 0.7 | −1.5 | 2.9 | .52 |
| Apical TR (deg/sec) | 8.5 | −0.5 | 17.4 | .06 | 12.1 | −1.8 | 25.9 | .08 | 4.9 | −6.9 | 16.7 | .40 |
| Apical UTR (deg/sec) | 1.6 | −8.8 | 12.0 | .76 | −14.6 | −30.5 | 1.4 | .07 | −0.6 | −13.2 | 12.1 | .93 |
| Time to peak apical UTR (% of diastole) | 10.6 | 6.8 | 14.4 | <.001 | 0.9 | −4.0 | 5.7 | .72 | 1.4 | −1.7 | 4.5 | .38 |
| LV twist | ||||||||||||
| Peak twist | −0.7 | −2.8 | 1.3 | .47 | −2.6 | −5.4 | 0.2 | .07 | −1.8 | −4.1 | 0.5 | .12 |
| Peak TR(deg/sec) | 7.3 | −5.3 | 20.0 | .25 | 2.5 | −13.3 | 18.3 | .74 | 4.8 | −10.8 | 20.3 | .53 |
| Peak UTR (deg/sec) | 9.6 | −3.9 | 23.1 | .16 | 3.4 | −16.5 | 23.3 | .73 | 15.2 | 1.2 | 29.3 | .03 |
| Time to peak UTR (% of diastole) | 5.8 | 1.9 | 9.7 | .004 | −0.3 | −5.1 | 4.5 | .91 | −1.7 | −4.8 | 1.4 | .27 |
| Variable | MIE, posttest vs baseline | HIIE, posttest vs baseline | HIIE vs MIE | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 95% CI | 95% CI | 95% CI | ||||||||||
| Estimate | Lower | Upper | P | Estimate | Lower | Upper | P | Estimate | Lower | Upper | P | |
| LV base | ||||||||||||
| Heart rate basal (beats/min) | −0.1 | −4.8 | 4.6 | .96 | −5.3 | −9.5 | −1.1 | .02 | −5.2 | −11.1 | 0.6 | .08 |
| Peak basal rotation | 1.2 | −0.6 | 2.9 | .19 | 1.2 | −0.4 | 2.9 | .13 | 0.1 | −1.9 | 2.1 | .94 |
| Basal TR (deg/sec) | 0.2 | −14.3 | 14.7 | .98 | 8.8 | −4.6 | 22.1 | .19 | 8.6 | −8.0 | 25.1 | .30 |
| Basal UTR (deg/sec) | −5.9 | −20.6 | 8.8 | .42 | −9.0 | −22.4 | 4.3 | .18 | −3.2 | −20.7 | 14.4 | .72 |
| Time to peak basal UTR (% of diastole) | −4.6 | −8.4 | −0.8 | .02 | −5.5 | −9.0 | −2.0 | .003 | −0.9 | −5.2 | 3.4 | .67 |
| LV apex | ||||||||||||
| Heart rate apical (beats/min) | −0.8 | −4.6 | 2.9 | .65 | −2.5 | −5.9 | 0.8 | .13 | −1.7 | −6.5 | 3.1 | .48 |
| Peak apical rotation | −0.4 | −2.3 | 1.4 | .64 | 1.0 | −0.7 | 2.7 | .25 | 1.4 | −0.9 | 3.8 | .23 |
| Apical TR (deg/sec) | 2.8 | −11.1 | 16.8 | .68 | −3.1 | −15.9 | 9.7 | .63 | −5.9 | −22.5 | 10.6 | .47 |
| Apical UTR (deg/sec) | −16.8 | −31.5 | −2.0 | .03 | −1.6 | −15.1 | 11.9 | .81 | 15.1 | −2.3 | 32.6 | .09 |
| Time to peak apical UTR (% of diastole) | −10.0 | −14.5 | −5.6 | <.001 | −8.8 | −12.9 | −4.7 | <.001 | 1.2 | −4.1 | 6.6 | .64 |
| LV twist | ||||||||||||
| Peak twist (deg) | −1.9 | −4.1 | 0.4 | .10 | −1.0 | −2.9 | 1.0 | .33 | 0.9 | −1.9 | 3.7 | .52 |
| Peak TR (deg/sec) | −4.5 | −22.3 | 13.2 | .61 | −2.7 | −18.9 | 13.6 | .74 | 1.8 | −19.0 | 22.7 | .86 |
| Peak UTR (deg/sec) | −4.1 | −19.7 | 11.4 | .59 | 4.3 | −9.8 | 18.3 | .54 | 8.4 | −11.0 | 27.8 | .39 |
| Time to peak UTR (% of diastole) | −6.5 | −10.6 | −2.5 | .002 | −7.7 | −11.3 | −4.1 | <.001 | −1.2 | −6.1 | 3.8 | .64 |
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