Exercise improves metformin 72-h glucose control by reducing the frequency of hyperglycemic peaks.

PURPOSE: To determine the separated and combined effects of metformin and exercise on insulin sensitivity and free-living glycemic control in overweight individuals with prediabetes/type 2 diabetes (T2DM). METHODS: We recruited 16 adults with BMI of 32.7 ± 4.3 kg m-2 and insulin resistance (HOMA-IR 3.2 ± 0.4) under chronic metformin treatment (1234 ± 465 g day-1) enrolled in a high-intensity interval training (HIIT) program. Participants underwent four 72-h experimental trials in a random-counterbalanced order: (1) maintaining their habitual metformin treatment (MET); (2) replacing metformin treatment by placebo (CON); (3) placebo plus two HIIT sessions (EX + CON), and (4) metformin plus two HIIT sessions (MET + EX). We used intermittently scanned continuous glucose monitoring (isCGM) during 72 h in every trial to obtain interstitial fluid glucose area under the curve (IFGAUC) and the percentage of measurements over 180 mg dL-1 (% IFGPEAKS). Insulin sensitivity was assessed on the last day of each trial with HOMA-IR index and calculated insulin sensitivity (CSI) from intravenous glucose tolerance test. RESULTS: IFGAUC was lower in MET + EX and MET than in CON (P = 0.011 and P = 0.025, respectively). In addition, IFGAUC was lower in MET + EX than in EX + CON (P = 0.044). %IFGPEAKS were only lower in MET + EX in relation to CON (P = 0.028). HOMA-IR and CSI were higher in CON in comparison with MET + EX (P = 0.011 and P = 0.022, respectively) and MET (P = 0.006 and P < 0.001, respectively). IFGAUC showed a significant correlation with HOMA-IR. CONCLUSION: Intense aerobic exercise in patients with diabetes and prediabetes under metformin treatment reduces free-living 72-h blood hyperglycemic peaks. This may help to prevent the development of cardiovascular complications associated with diabetes.

Insulin sensitivity improvement with exercise training is mediated by body weight loss in subjects with metabolic syndrome.

AIM: To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL). METHODS: Subjects (aged 55±8 years) with metabolic syndrome (MetS), prediabetes (fasting blood glucose: 111±2mg·dL-1, HbA1c: 5.85±0.05%) and abdominal obesity (waist circumference: 104±7.9cm) were randomly allocated to either a group performing aerobic interval training (EXER; n=76) or a sedentary group receiving lifestyle counselling (CONT; n=20) for 16 weeks. RESULTS: At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CSI), body composition and VO2max were similar between the groups. After the intervention, both groups had similar BWL (1-2%), but only the EXER group showed decreased [mean (95% CI)] trunk fat mass [from 18.2 (17.4-18.9) to 17.3kg (16.6-17.9); P<0.001] and HOMA2 scores [from 1.6 (1.5-1.7) to 1.4 (1.3-1.5); P=0.001], and increased VO2max [from 2.07 (1.92-2.21) to 2.28 (2.11-2.45) LO2·min-1; P<0.001]. However, CSI did not improve in any group. Within-group subdivision by BWL (≤0%, 0-3%, ≥3%) revealed higher CSI in those with BWL≥3% in both groups. Trunk fat mass reductions were closely associated with CSI and HOMA-IR improvement (r=-0.452-0.349; P<0.001). CONCLUSION: In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.

Weight loss but not gains in cardiorespiratory fitness after exercise-training predicts improved health risk factors in metabolic syndrome.

BACKGROUND AND AIMS: To examine the relationship between changes in cardiorespiratory fitness (CRF; estimated by VO2max) and metabolic syndrome (MetS) after an exercise training intervention to confirm/contradict the high association found in cross-sectional observational studies. METHODS AND RESULTS: MetS individuals (54 ± 8 yrs old; BMI of 32 ± 5) were randomly allocated (6:1 ratio) to a group that exercised trained for 16-weeks (EXER; n = 138) or a control sedentary group (CONT; n = 22). At baseline, MetS components, body composition and exercise responses were similar between groups (all P > 0.05). After 16 weeks of intervention, only EXER reduced body weight, waist circumference (-1.21 ± 0.22 kg and -2.7 ± 0.3 cm; P < 0.001), mean arterial blood pressure and hence the composite MetS Z-score (-7.06 ± 0.77 mmHg and -0.21 ± 0.03 SD; P < 0.001). In the EXER group, CRF increased by 16% (0.302 ± 0.026, 95% CI 0.346 to 0.259 LO2·min-1; P < 0.001) but was not a significant predictor of MetS Z-score improvements (r = -0.231; ß = -0.024; P = 0.788). Instead, body weight reductions predicted 25% of MetS Z-score changes (r = 0.508; ß = 0.360; P = 0.001). CONCLUSIONS: In MetS individuals, the exercise-training increases in CRF are not predictive of the improvements in their health risk factors. Instead, body weight loss (<2%) was a significant contributor to the improved MetS Z-score and thus should be emphasized in exercise training programs. ClinicalTrials.gov identifier: NCT03019796.

Effects of intense aerobic exercise and/or antihypertensive medication in individuals with metabolic syndrome.

We studied the blood pressure lowering effects of a bout of exercise and/or antihypertensive medicine with the goal of studying if exercise could substitute or enhance pharmacologic hypertension treatment. Twenty-three hypertensive metabolic syndrome patients chronically medicated with angiotensin II receptor 1 blockade antihypertensive medicine underwent 24-hr monitoring in four separated days in a randomized order; (a) after taking their habitual dose of antihypertensive medicine (AHM trial), (b) substituting their medicine by placebo medicine (PLAC trial), (c) placebo medicine with a morning bout of intense aerobic exercise (PLAC+EXER trial) and (d) combining the exercise and antihypertensive medicine (AHM+EXER trial). We found that in trials with AHM subjects had lower plasma aldosterone/renin activity ratio evidencing treatment compliance. Before exercise, the trials with AHM displayed lower systolic (130 ± 16 vs 133 ± 15 mm Hg; P = .018) and mean blood pressures (94 ± 11 vs 96 ± 10 mm Hg; P = .036) than trials with placebo medication. Acutely (ie, 30 min after treatments) combining AHM+EXER lowered systolic blood pressure (SBP) below the effects of PLAC+EXER (-8.1 ± 1.6 vs -4.9 ± 1.5 mm Hg; P = .015). Twenty-four hour monitoring revealed no differences among trials in body motion. However, PLAC+EXER and AHM lowered SBP below PLAC during the first 10 hours, time at which PLAC+EXER effects faded out (ie, at 19 PM). Adding exercise to medication (ie, AHM+EXER) resulted in longer reductions in SBP than with exercise alone (PLAC+EXER). In summary, one bout of intense aerobic exercise in the morning cannot substitute the long-lasting effects of antihypertensive medicine in lowering blood pressure, but their combination is superior to exercise alone.

Aerobic interval training reduces vascular resistances during submaximal exercise in obese metabolic syndrome individuals.

PURPOSE: The aim of this study was to determine the effects of high-intensity aerobic interval training (AIT) on exercise hemodynamics in metabolic syndrome (MetS) volunteers. METHODS: Thirty-eight, MetS participants were randomly assigned to a training (TRAIN) or to a non-training control (CONT) group. TRAIN consisted of stationary interval cycling alternating bouts at 70-90% of maximal heart rate during 45 min day-1 for 6 months. RESULTS: CONT maintained baseline physical activity and no changes in cardiovascular function or MetS factors were detected. In contrast, TRAIN increased cardiorespiratory fitness (14% in VO2PEAK; 95% CI 9-18%) and improved metabolic syndrome (-42% in Z score; 95% CI 83-1%). After TRAIN, the workload that elicited a VO2 of 1500 ml min-1 increased 15% (95% CI 5-25%; P < 0.001). After TRAIN when subjects pedaled at an identical submaximal rate of oxygen consumption, cardiac output increased by 8% (95% CI 4-11%; P < 0.01) and stroke volume by 10% (95% CI, 6-14%; P < 0.005) being above the CONT group values at that time point. TRAIN reduced submaximal exercise heart rate (109 ± 15-106 ± 13 beats min-1; P < 0.05), diastolic blood pressure (83 ± 8-75 ± 8 mmHg; P < 0.001) and systemic vascular resistances (P < 0.01) below CONT values. Double product was reduced only after TRAIN (18.2 ± 3.2-17.4 ± 2.4 bt min-1 mmHg 10-3; P < 0.05). CONCLUSIONS: The data suggest that intense aerobic interval training improves hemodynamics during submaximal exercise in MetS patients. Specifically, it reduces diastolic blood pressure, systemic vascular resistances, and the double product. The reduction in double product, suggests decreased myocardial oxygen demands which could prevent the occurrence of adverse cardiovascular events during exercise in this population. CLINICALTRIALS. GOV IDENTIFIER: NCT03019796.

Ambulatory blood pressure response to a bout of HIIT in metabolic syndrome patients.

PURPOSE: The effectiveness of exercise to lower blood pressure may depend on the type and intensity of exercise. We study the short-term (i.e., 14-h) effects of a bout of high-intensity aerobic interval training (HIIT) on blood pressure in metabolic syndrome (MetS) patients. METHODS: Nineteen MetS patients (55.2 ± 7.3 years, 6 women) entered the study. Eight of them were normotensive and eleven hypertensive according to MetS threshold (≥130 mmHg for SBP and/or ≥85 mmHg for DBP). In the morning of 3 separated days, they underwent a cycling exercise bout of HIIT (>90% of maximal heart rate, ~85% VO2max), or a bout of isocaloric moderate-intensity continuous training (MICT; ~70% of maximal heart rate, ~60% VO2max), or a control no-exercise trial (REST). After exercise, ambulatory blood pressure (ABP; 14 h) was monitored, while subjects continued their habitual daily activities wearing a wrist-band activity monitor. RESULTS: No ABP differences were found for normotensive subjects. In hypertensive subjects, systolic ABP was reduced by 6.1 ± 2.2 mmHg after HIIT compared to MICT and REST (130.8 ± 3.9 vs. 137.4 ± 5.1 and 136.4 ± 3.8 mmHg, respectively; p < 0.05). However, diastolic ABP was similar in all three trials (77.2 ± 2.6 vs. 78.0 ± 2.6 and 78.9 ± 2.8 mmHg, respectively). Motion analysis revealed no differences among trials during the 14-h. CONCLUSION: This study suggests that the blood pressure reducing effect of a bout of exercise is influence by the intensity of exercise. A HIIT exercise bout is superior to an equivalent bout of continuous exercise when used as a non-pharmacological aid in the treatment of hypertension in MetS.