A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals.

We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating carbohydrate oxidation and glycogen use would increase the disposal of an ingested glucose load [i.e., oral glucose tolerance test (OGTT); 75 g of glucose]. Separated by at least 1 wk, nine young healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58 ± 5% V̇o2max either in a thermoneutral (21 ± 1°C; NEUTRAL) or in a hot environment (33 ± 1°C; HEAT) eliciting similar energy expenditure (503 ± 101 kcal). These two trials were compared with a no-exercise trial (NO EXER). Twenty minutes after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149 ± 35 vs. 124 ± 31 µmol·kg-1·min-1, P = 0.010). However, during the following OGTT, glucose Rd was similar in HEAT and NEUTRAL trials (i.e., 25.1 ± 3.6 vs. 25.2 ± 5.3 µmol·kg-1·min-1, P = 0.981). Insulin sensitivity (i.e., ISIndexMATSUDA) only improved in NEUTRAL compared with NO EXER (10.1 ± 4.6 vs. 8.8 ± 3.7 au; P = 0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.NEW & NOTEWORTHY Exercise in the heat increases estimated muscle glycogen use. Reduced muscle glycogen after exercise in the heat could increase insulin-mediated glucose uptake during a subsequent oral glucose tolerance test (OGTT). However, plasma glucose kinetics are not improved during the OGTT in response to a bout of exercise in the heat, and insulin sensitivity worsens. Heat stress activates glucose counterregulatory hormones whose actions may linger during the OGTT, preventing increased glucose uptake.

Glucose volume of distribution affects insulin sensitivity measured by intravenous glucose tolerance test.

AIM: To determine whether glucose volume of distribution (VdGLUCOSE ) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). METHODS: Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2 ·kg-1 ·min-1 ; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time-response curve. RESULTS: VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg-1 ; p < 0.001). VdGLUCOSE was a strong predictor of IS (ß standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = -0.548 and -0.555, respectively; p < 0.001). CONCLUSIONS: Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat-free mass rather than body weight for a more accurate diagnosis of impaired IS.

Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial.

A supervised intense aerobic exercise program improves the health of individuals with metabolic syndrome (MetS). However, it is unclear whether the timing of training within the 24 h day would influence those health benefits. The present study aimed to determine the influence of morning vs. afternoon exercise on body composition, cardiometabolic health and components of MetS. One hundred thirty-nine individuals with MetS were block randomized into morning (AMEX; n = 42) or afternoon (PMEX; n = 59) exercise training groups, or a non-training control group (Control; n = 38). Exercise training was comprised of 48 supervised high-intensity interval sessions distributed over 16 weeks. Body composition, cardiorespiratory fitness (assessed by V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ ), maximal fat oxidation (FOmax ), blood pressure and blood metabolites were assessed before and after the intervention. Compared with the non-training Control, both exercise groups improved similarly body composition (-0.7% fat loss; P = 0.002), waist circumference (-2.1 cm; P < 0.001), diastolic blood pressure (-3.8 mmHg; P = 0.004) and V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ (3.5 mL kg-1   min-1 ; P < 0.001) with no differences between training groups. AMEX, in comparison with PMEX, reduced systolic blood pressure (-4% vs. -1%; P = 0.019), plasma fasting insulin concentration (-12% vs. -5%; P = 0.001) and insulin resistance (-14% vs. -4%; P = 0.006). Furthermore, MetS Z score was further reduced in the AMEX compared to PMEX (-52% vs. -19%; P = 0.021) after training. In summary, high-intensity aerobic exercise training in the morning in comparison to training in the afternoon is somewhat more efficient at reducing cardiometabolic risk factors (i.e. systolic blood pressure and insulin sensitivity). KEY POINTS: The effect of exercise time of day on health promotion is an area that has gained interest in recent years; however, large-scale, randomized-control studies are scarce. People with metabolic syndrome (MetS) are at risk of developing cardiometabolic diseases and reductions in this risk with exercise training can be precisely gauged using a compound score sensitive to subtle evolution in each MetS component (i.e. Z score). Supervised aerobic exercise for 16 weeks (morning and afternoon), without dietary restriction, improved cardiorespiratory and metabolic fitness, body composition and mean arterial pressure compared to a non-exercise control group. However, training in the morning, without changes in exercise dose or intensity, reduced systolic blood pressure and insulin resistance further compared to when training in the afternoon. Thus, high-intensity aerobic exercise training in the morning is somewhat more efficient in improving the health of individuals with metabolic syndrome.

Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-diabetic and diabetic adults.

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre-diabetes and type 2 diabetes (T2D). Eight T2D adults (60 ± 4 yr) with overweight/obesity (32 ± 4 kg·m-2) under chronic metformin treatment (9 ± 6 yr; 1281 ± 524 mg·day-1) underwent four trials; 1) taking their habitual metformin treatment (MET), 2) substituting during 96 h their metformin medication by placebo (PLAC), 3) placebo combined with 50 min bout of high-intensity interval exercise (PLAC + EX), and 4) metformin combined with exercise (MET + EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET + EX lower than PLAC and PLAC + EX, respectively; P = 0.023). MET + EX increased MATSUDAindex above PLAC (4.8 ± 1.4 vs. 3.3 ± 1.0, respectively; P = 0.018) and OGISindex above PLAC (358 ± 52 vs. 306 ± 46 mL·min-1·m-2, respectively; P = 0.006). Metformin decreased the plasma appearance of the ingested glucose (Ra OGTT; MET vs. PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg-1·min-1; P = 0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre-diabetes and type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise.NEW & NOTEWORTHY Metformin is the most prescribed oral antidiabetic medicine in the world but its mechanism of action and its interactions with exercise are not fully understood. Our stable isotope tracer data suggested that metformin reduces the rates of oral glucose entering the circulation (gut-liver effect). Exercise, in turn, tended to reduce postprandial insulin blood levels potentiating metformin improvements in insulin sensitivity. Thus, exercise potentiates metformin improvements in glycemic control and should be advised to metformin users.

Chronic Statin Treatment Does Not Impair Exercise Lipolysis or Fat Oxidation in Exercise-Trained Individuals With Obesity and Dyslipidemia.

OBJECTIVE: To determine whether statin medication in individuals with obesity, dyslipidemia, and metabolic syndrome affects their capacity to mobilize and oxidize fat during exercise. METHODS: Twelve individuals with metabolic syndrome pedaled during 75 min at 54 ± 13% V˙O2max (5.7 ± 0.5 metabolic equivalents) while taking statins (STATs) or after 96-hr statin withdrawal (PLAC) in a randomized double-blind fashion. RESULTS: At rest, PLAC increased low-density lipoprotein cholesterol (i.e., STAT 2.55 ± 0.96 vs. PLAC 3.16 ± 0.76 mmol/L; p = .004) and total cholesterol blood levels (i.e., STAT 4.39 ± 1.16 vs. PLAC 4.98 ± 0.97 mmol/L; p = .008). At rest, fat oxidation (0.99 ± 0.34 vs. 0.76 ± 0.37 µmol·kg-1·min-1 for STAT vs. PLAC; p = .068) and the rates of plasma appearance of glucose and glycerol (i.e., Ra glucose-glycerol) were not affected by PLAC. After 70 min of exercise, fat oxidation was similar between trials (2.94 ± 1.56 vs. 3.06 ± 1.94 µmol·kg-1·min-1, STA vs. PLAC; p = .875). PLAC did not alter the rates of disappearance of glucose in plasma during exercise (i.e., 23.9 ± 6.9 vs. 24.5 ± 8.2 µmol·kg-1·min-1 for STAT vs. PLAC; p = .611) or the rate of plasma appearance of glycerol (i.e., 8.5 ± 1.9 vs. 7.9 ± 1.8 µmol·kg-1·min-1 for STAT vs. PLAC; p = .262). CONCLUSIONS: In patients with obesity, dyslipidemia, and metabolic syndrome, statins do not compromise their ability to mobilize and oxidize fat at rest or during prolonged, moderately intense exercise (i.e., equivalent to brisk walking). In these patients, the combination of statins and exercise could help to better manage their dyslipidemia.

Statins effect on insulin resistance after a meal and exercise in hypercholesterolemic pre-diabetic individuals.

AIM: To study if statins, a widely prescribed, inexpensive medication to prevent coronary artery diseases may cause insulin resistance (IR). METHODS: Fasted (HOMA-IR) and post-meal insulin resistance were assessed in 21 pre-diabetic hypercholesterolemic individuals treated with statins (STA trial). Measurements were compared to another trial conducted 96 h after statin withdrawal using placebo pills (PLAC trial). Trials were duplicated 16-18 h after a bout of moderate-intensity exercise (500 kcal of energy expenditure) to reduce IR and better appreciate statin effects (EXER+STA and EXER+PLAC trials). RESULTS: Statin withdrawal did not affect fasting (HOMA-IR; 2.35 ± 1.05 vs. 2.18 ± 0.87 for STA vs. PLAC trials; p = 0.150) or post-meal insulin resistance (i.e., Matsuda-index, STA 6.23 ± 2.83 vs. PLAC 6.49 ± 3.74; p = 0.536). A bout of aerobic exercise lowered post-meal IR (p = 0.043), but statin withdrawal did not add to the exercise actions (p = 0.564). Statin withdrawal increased post-meal plasma free glycerol concentrations (0.136 ± 0.073 vs. 0.185 ± 0.090 mmol·L-1 for STA vs. PLAC trials; p < 0.001) but not plasma free fatty acids or fat oxidation (p = 0.981, and p = 0.621, respectively). Post-meal fat oxidation was higher in the exercise trials (p = 0.002). CONCLUSIONS: Withdrawal of statin medication does not affect fasting or post-meal insulin resistance in pre-diabetic hypercholesterolemic individuals. Furthermore, statin use does not interfere with the beneficial effects of exercise on lowering IR.

Endurance Exercise Training reduces Blood Pressure according to the Wilder's Principle.

The effect of antihypertensive medicine (AHM) is larger the higher the pre-treatment blood pressure level. It is unknown whether this Wilder's principle, also applies for the exercise-training blood pressure (BP) lowering effect. One hundred seventy-eight (n=178) middle-aged individuals (55±8 y) with metabolic syndrome (MetS), underwent high intensity interval training (3 days·week-1) for 16 weeks. Participants were divided into medicated (Med; n=103) or not medicated (No Med; n=75) with AHM. Office BP was evaluated before and after the exercise-training. Correlations and stepwise regression analysis were used to determine which variable better predicted the reductions in systolic BP (SBP) with training. After training, participants with hypertension lowered SBP by a similar magnitude regardless of if they were in the Med (-15 mmHg, 95% CI-12,-19; P<0.001) or No Med group (-13 mmHg, 95% CI-9,-16; P<0.001). However, SBP did not decrease among normotensive groups (P=0.847 for Med and P=0.937 for No Med). Pre-treatment SBP levels was the best predictor of exercise-training lowering effect (r=-0.650; ß=-0.642; P<0.001). For each 10 mmHg higher pre-training SBP there were a 5 mmHg deeper SBP reduction (Wilder principle). Furthermore, AHM does not interfere with exercise-training BP-lowering effect.

Effects of statins and exercise on postprandial lipoproteins in metabolic syndrome vs metabolically healthy individuals.

AIMS: To determine if the combination of exercise and statin could normalize postprandial triglyceridaemia (PPTG) in hypercholesteraemic individuals. METHODS: Eight hypercholesteraemic (blood cholesterol 182 ± 38 mg dL-1 ; low-density lipoprotein-cholesterol [LDL-c] 102 ± 32 mg dL-1 ) overweight (body mass index 30 ± 4 kg m-2 ) individuals with metabolic syndrome (MetS) were compared to a group of 8 metabolically healthy (MetH) controls (blood cholesterol 149 ± 23 mg dL-1 ; LDL-c 77 ± 23 mg dL-1 , and body mass index 23 ± 2 kg m-2 ). Each group underwent 2 PPTG tests, either 14 hours after a bout of intense exercise or without previous exercise. Additionally, MetS individuals were tested 96 hours after withdrawal of their habitual statin medication to study medication effects. RESULTS: A bout of exercise before the test meal did not reduce PPTG in MetS (P = .347), but reduced PPTG by 46% in MetH (413 ± 267 to 224 ± 142 mg dL-1 for 5 h incremental area under the curve; P = .02). In both trials (i.e., either after a bout of intense exercise or without previous exercise), statin withdrawal in MetS greatly increased PPTG (average 65%; P < .01), mean LDL-c (average 25%; P < .01), total cholesterol (average 16%; P < .01) and apolipoprotein (Apo) B48 (24%; P < .01), without interference from exercise. However, Apo B100 was not affected by statin withdrawal. CONCLUSION: Hypercholesteraemic MetS individuals (compared to MetH controls) fail to show an effect of exercise on reducing PPTG. However, chronic statin medication blunts the elevations in triglyceride after a fat meal (i.e., incremental area under the curve of PPTG) reducing their cardiovascular risk associated with their atherogenic dyslipidaemia. Statin decreases PPTG by reducing the secretion or accelerating the catabolism of intestinal Apo B48.

Concurrent endurance and resistance training enhances muscular adaptations in individuals with metabolic syndrome.

The purpose of the study was to determine if concurrent training (endurance and resistance in a single session) elicits leg muscular adaptations beyond the ones obtained by endurance training alone in sedentary individuals with metabolic syndrome (MetS). Sixty-six MetS individuals (37% women, age 56 ± 7 years, BMI 32 ± 5 kg m-2 and 3.8 ± 0.8 MetS factors) were randomized to undergo one of the following 16-week isocaloric exercise programs: (i) 4 + 1 bouts of 4 min at 90% of HRMAX of intense aerobic cycling (IAC + IAC group; n = 33), (ii) 4 IAC bouts followed by 3 sets of 12 repetitions of 3 lower-limb free-weight exercises (IAC + RT group; n = 33). We measured the effects of training on maximal cycling power, leg press maximum strength (1RM), countermovement jump height (CMJ), and mean propulsive velocity (MPV) at workloads ranging from 10% to 100% of baseline 1RM leg press. After intervention, MetS components (Z-score) improved similarly in both groups (p = 0.002). Likewise, maximal cycling power during a ramp test improved similarly in both groups (time effect p < 0.001). However, leg press 1RM improved more in IAC + RT than in IAC + IAC (47 ± 5 vs 13 ± 5 kg, respectively, interaction p < 0.001). CMJ only improved with IAC + RT (0.8 ± 0.2 cm, p = 0.001). Leg press MPV at heavy loads (ie, 80%-100% 1RM) improved more with concurrent training (0.12 ± 0.01 vs 0.06 ± 0.02 m s-1 , interaction p = 0.013). In conclusion, in unconditioned MetS individuals, intense aerobic cycling alone improves leg muscle performance. However, substituting 20% of intense aerobic cycling by resistance training further improves 1RM leg press, MPV at high loads, and jumping ability while providing similar improvement in MetS components.

Effects of antihypertensive medication and high-intensity interval training in hypertensive metabolic syndrome individuals.

Pharmacological and non-pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (ie, metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (ie, exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, 36 hypertensive individuals with metabolic syndrome (MetS) under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after 4 months of high-intensity interval training (HIIT), participants completed two trials in a double-blind, randomized order: (a) placebo trial consisting of AHM withdrawal for 3 days and (b) AHM trial where individuals held their habitual dose of AHM. In each trial, 24-h mean arterial pressure (MAP) was monitored and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin-to-creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24-h MAP (-5.7 mmHg, p < 0.001 and -2.3 mmHg, p = 0.007, respectively). However, there was not interaction between AHM and HIIT on 24-h MAP (p = 0.240). There was a main effect of AHM increasing PRA (p < 0.001) but no effect on plasma aldosterone concentration (p = 0.368). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.

Effects of statin therapy and exercise on postprandial triglycerides in overweight individuals with hypercholesterolaemia.

AIMS: To determine the effects of statins on postprandial lipaemia (PPL) and to study if exercise could enhance statin actions. METHODS: Ten hypercholesteraemic (blood cholesterol 204 ± 36 mg dL-1 ; low-density lipoprotein-cholesterol 129 ± 32 36 mg dL-1 ) overweight (body mass index 30 ± 4 kg m-2 ), metabolic syndrome individuals chronically medicated with statins (>6 months) underwent 5-hour PPL tests in 4 occasions in a randomized order: (i) substituting their habitual statin medication by placebo for 96 hours (PLAC trial); (ii) taking their habitual statin medicine (STA trial); (iii) placebo combined with a bout of intense aerobic exercise (EXER+PLAC trial); and (iv) combining exercise and statin medicine (EXER+STA trial). RESULTS: Before the fat meal, statin withdrawal (i.e. PLAC and EXER+PLAC) increased blood triglycerides (TG; 24%), low-density lipoprotein-cholesterol (31%) and total cholesterol (19%; all P < .05) evidencing treatment compliance. After the meal, statin withdrawal increased 5-hour postprandial TG (PPTG) compared to its matched trials (94% higher PLAC vs STA and 45% higher EXER+PLAC vs EXER+STA; P < .05). EXER+PLAC trial did not lower PPTG below PLAC (i.e. incremental AUC of 609 ± 152 vs 826 ± 190 mg dL-1 5 h; P = .09). Adding exercise to statin did not result in larger reductions in PPTG (i.e. EXER+STA vs STA incremental area under the curve of 421 ± 87 vs 421 ± 84 mg dL-1 5 h; P = .99). CONCLUSION: In hypercholesteraemic metabolic syndrome individuals, chronic statin therapy blunts the elevations in TG after a fat meal (i.e. incremental area under the curve of PPTG) reducing the cardiovascular risk associated to their atherogenic dyslipidaemia. However, a single bout of intense aerobic exercise before the high fat meal, does not reduce PPTG but also does not interfere with the effects of statin treatment.

Importance of a verification test to accurately assess V̇O2 max in unfit individuals with obesity.

BACKGROUND: To determine the trustworthiness of graded exercise test to exhaustion (GXT) to assess maximal oxygen uptake ( V ˙ O 2 max ) in metabolic syndrome individuals with obesity and poor cardiorespiratory fitness. METHODS: V ˙ O 2 max was assessed in 100 metabolic syndrome adults (57 ± 8 years; 34% women), with obesity (BMI 32 ± 5 kg·m-2 ) using GXT followed by supramaximal constant-load verification test (VerT) at 110% of maximal GXT work rate. V ˙ O 2 data from GXT and VerT were compared using paired t test and plotted for Bland-Altman analysis. GXT sensitivity and specificity to detect V ˙ O 2 max were also calculated. RESULTS: Seventy individuals did not achieve V ˙ O 2 plateau during GXT. GXT underestimated V ˙ O 2 max in 40 subjects. In these subjects, the magnitude of V ˙ O 2 max underestimation with GXT was 9% (167 mLO2 ·min-1 ; P < .001). In the whole sample (n = 100), bias error differences between GXT and VerT was 63 mLO2 ·min-1 (3% underestimation). This error was constant regardless of differences in fitness levels among individuals (R = -0.07; homoscedasticity). GXT results were unreliable in 62% of the sample with 16% of false-positive and 46% of false-negative results. Sensitivity and specificity of GTX to assess V ˙ O 2 max were low (ie, 23% and 60%, respectively). CONCLUSION: Our data indicate that the magnitude (3%-9%) and prevalence (40% of subjects) of V ˙ O 2 max underestimation with the use of a GXT alone is high in a large sample of unfit metabolic syndrome individuals with obesity. Our data advocate for the need of using VerT after GXT to avoid significant cardiorespiratory fitness underestimation in metabolic syndrome individuals with obesity and low fitness level.

Post-exercise Hypotension Produced by Supramaximal Interval Exercise is Potentiated by Angiotensin Receptor Blockers.

We studied the effects of supramaximal interval exercise (SIE) with or without antihypertensive medication (AHM) on 21-hr blood pressure (BP) response. Twelve hypertensive patients chronically medicated with AHM, underwent three trials in a randomized order: a) control trial without exercise and substituting their AHM with a placebo (PLAC); b) placebo medicine and a morning bout of SIE (PLAC+SIE), and c) combining AHM and exercise (AHM+SIE). Acute and ambulatory blood pressure responses were measured for 21-hr after treatment. 20 min after treatment, systolic blood pressure (SBP) readings were reduced, similar to readings after PLAC+SIE (-9.7±6.0 mmHg, P<0.001) and AHM+SIE (-10.4±7.9 mmHg, P=0.001). 21 h after treatment, SBP remained reduced after PLAC+SIE (125±12 mmHg, P=0.022) and AHM+SIE (122±12 mmHg, P=0.013) compared to PLAC (132±16 mmHg). The BP reduction in PLAC+SIE faded out at 4 a.m., while in AHM+SIE it continued overnight. At night, BP reduction was larger in AHM+SIE than PLAC+SIE (-5.6±4.0 mmHg, P=0.006). Our data shows that a bout of supramaximal aerobic interval exercise in combination with ARB medication in the morning elicits a sustained blood pressure reduction lasting at least 21-h. Thus, the combination of exercise and angiotensin receptor blocker medication seems superior to exercise alone for acutely decreasing blood pressure.

Acute Hypotension after High-Intensity Interval Exercise in Metabolic Syndrome Patients.

The purpose of this study was to compare the magnitude of post-exercise hypotension (PEH) after a bout of cycling exercise using high-intensity interval training (HIIT) in comparison to a bout of traditional moderate-intensity continuous exercise (CE). After supine rest 14 obese (31±1 kg·m-2) middle-age (57±2 y) metabolic syndrome patients (50% hypertensive) underwent a bout of HIIT or a bout of CE in a random order and then returned to supine recovery for another 45 min. Exercise trials were isocaloric and compared to a no-exercise trial (CONT) of supine rest for a total of 160 min. Before and after exercise we assessed blood pressure (BP), heart rate (HR), cardiac output (Q), systemic vascular resistance (SVR), intestinal temperature (TINT), forearm skin blood flow (SKBF) and percent dehydration. HIIT produced a larger post-exercise reduction in systolic blood pressure than CE in the hypertensive group (-20±6 vs. -5±3 mmHg) and in the normotensive group (-8±3 vs. -3±2 mmHg) while HIIT reduced SVR below CE (P<0.05). Percent dehydration was larger after HIIT, and post-exercise TINT and SKBF increased only after HIIT (all P<0.05). Our findings suggest that HIIT is a superior exercise method to CE to acutely reduce blood pressure in MSyn subjects.

Effects of Statins on Fat Oxidation Improvements After Aerobic Exercise Training.

CONTEXT: Statins blunt cardiorespiratory fitness improvements after exercise training and may affect fat oxidation adaptations to training. OBJECTIVE: To determine if long-term statin use in dyslipidemic individuals restricts the improvements in fat oxidation typically observed after an intense exercise-training program. METHODS: A total of 106 metabolic syndrome individuals either chronically medicated with statins (ie, statin group; n = 46) or statin naive (ie, control group; n = 60) completed a 16-week supervised high-intensity interval training program. Maximal rates of oxygen consumption (V˙O2MAX), fat oxidation (FOMAX), and the shape of the workload-fat oxidation curve were assessed before and 48 hours after training in an overnight fasted state. RESULTS: Starting from a similar value at baseline, both groups increased V˙O2MAX after training, but the increase was larger in the control than in the statin group (19.4% vs 12.6%; P = .013). Before training, FOMAX in the statin group was lower (0.19 ± 0.08 vs 0.23 ± 0.07 g·min-1; P = .023) and took place at a lower workload (33 ± 21 vs 37 ± 19 W; P = .015) than in the control group. After training, FOMAX improved similarly in both groups (0.06 ± 0.08; 95% CI, 0.03-0.08 g·min-1 and 0.05 ± 0.09; 95% CI, 0.03-0.07 g·min-1, for statin and control groups, respectively; (P < .001). Still, after training, FOMAX occurred at a 28% lower workload in the statin group (38 ± 26 vs 53 ± 32 W; P = .048). The V˙O2-workload slope decreased after training in both groups (both P < .001) along with reductions in the respiratory exchange ratio-workload slope. Fat oxidation increased at all workloads after training regardless of the use of statins. CONCLUSION: Long-term statin treatment is associated with blunted exercise fat oxidation before exercise training. However, statin use does not attenuate the improvements in exercise fat oxidation (FOMAX) derived from intense aerobic exercise training. This finding should encourage statin users to exercise-train to benefit from increased fat oxidation once their fitness level improves.

Effect of Yearly Exercise on Medication Expense and Benefit-Cost Ratio in Individuals with Metabolic Syndrome: A Randomized Clinical Trial.

INTRODUCTION: Lifestyle modification through incorporation of exercise training could improve metabolic syndrome (MetS) clinical components (hypertension, dyslipidemia, hyperglycemia, and visceral abdominal obesity). We aimed to assess if long-term exercise training could restrain the increased pharmacological cost of the clinical management of the MetS. METHODS: Medicine cost during a 5-yr-long randomized controlled exercise intervention trial was analyzed. After a per-protocol analysis, a group of 64 individuals 53 ± 2 yr old, with overweight (body mass index, 33.4 ± 0.9 kg·m -2 ) and MetS (3.6 ± 0.2 factors) were randomized to a training (4 months·yr -1 for 5 yr; EXERCISE, n = 25) or to a control group (CONTROL, n = 26). Subjects were studied on three occasions during the 5-yr follow-up. Participants continued their routine medication managed by their general practitioner. The main outcome is the 5-yr evolution of medication cost to treat MetS (hyperglycemia, hypertension, and hyperlipidemia). A secondary outcome is the benefit-cost ratio of the exercise intervention. RESULTS: In CONTROL, medicine cost increased 160% from baseline ( P < 0.001), whereas in EXERCISE, it remained unchanged (33%; P = 0.25). After the 5-yr follow-up, medicine use was 60% and medicine cost 74% higher in CONTROL than EXERCISE ( P < 0.05 in both cases). However, MetS z score was similarly reduced over time in both groups ( P = 0.244 for group-time interaction). The number of prescribed medications increased after 5 yr in CONTROL (89%; P < 0.001), whereas it remained stable with yearly training (17%; P = 0.72 in EXERCISE). Ten-year atherosclerotic cardiovascular disease risk estimation increased only in CONTROL (15%; P = 0.05 for group-time interaction). The benefit in medicine savings (€153 per year and patient) triplicated the estimated cost (€50.8 per year and patient) of the exercise intervention. CONCLUSIONS: A 5-yr-long supervised exercise training program in middle-age individuals with MetS prevents the need for increasing medicine use. The savings in pharmacological therapy outweighs the estimated costs of implementing the exercise program.

Effects of statin therapy on glycemic control and insulin resistance: A systematic review and meta-analysis.

AIMS: To update the evidence about the diabetogenic effect of statins. METHODS: We searched for randomized-controlled trials reporting the effects of statin therapy on glycosylated hemoglobin (HbA1c) and/or homeostatic model insulin resistance (i.e., HOMA-IR) as indexes of diabetes. Studies were classified between the ones testing normal vs individuals with already altered glycemic control (HbA1c ≥ 6.5%; and HOMA-IR ≥ 2.15). Furthermore, studies were separated by statin type and dosage prescribed. Data are presented as mean difference (MD) and 95% confidence intervals. RESULTS: A total of 67 studies were included in the analysis (>25,000 individuals). In individuals with altered glycemic control, statins increased HbA1c levels (MD 0.21%, 95% CI 0.16-to-0.25) and HOMA-IR index (MD 0.31, 95% CI 0.24-to-0.38). In individuals with normal glycemic control, statin increased HbA1c (MD 1.33%, 95% CI 1.31-to-1.35) and HOMA-IR (MD 0.49, 95% CI 0.41-to-0.58) in comparison to the placebo groups. The dose or type of statins did not modulate the diabetogenic effect. CONCLUSIONS: Statins, slightly but significantly raise indexes of diabetes in individuals with adequate or altered glycemic control. The diabetogenic effect does not seem to be influenced by the type or dosage of statin prescribed.

Acute Statin Withdrawal Does not Interfere With the Improvements of a Session of Exercise in Postprandial Metabolism.

BACKGROUND: The risk for atherogenic plaque formation is high after ingestion of meals in individuals with high blood lipid levels (ie, dyslipidemia). Statins and exercise reduce the rise of blood triglyceride concentrations after a meal, but the effect of their combination is unclear. METHODS: In a randomized crossover design, 11 individuals with dyslipidemia and metabolic syndrome treated with statins underwent a mixed-meal (970 ± 111 kcal, 24% fat, and 34% carbohydrate) tolerance test. Plasma lipid concentrations, fat oxidation, glucose, and glycerol kinetics were monitored immediately prior and during the meal test. Trials were conducted with participants under their habitual statin treatment and 96 hours after blinded statin withdrawal. Trials were duplicated after a prolonged bout of low-intensity exercise (75 minutes at 53 ± 4% maximal oxygen consumption) to study the interactions between exercise and statins. RESULTS: Statins reduced postprandial plasma triglycerides from 3.03 ± 0.85 to 2.52 ± 0.86 mmol·L-1 (17%; P = .015) and plasma glycerol concentrations (ie, surrogate of whole-body lipolysis) without reducing plasma free fatty acid concentration or fat oxidation. Prior exercise increased postprandial plasma glycerol levels (P = .029) and fat oxidation rates (P = .024). Exercise decreased postprandial plasma insulin levels (241 ± 116 vs 301 ± 172 ρmol·L-1; P = .026) but not enough to increase insulin sensitivity (P = .614). Neither statins nor exercise affected plasma glucose appearance rates from exogenous or endogenous sources. CONCLUSIONS: In dyslipidemic individuals, statins reduce blood triglyceride concentrations after a meal, but without limiting fat oxidation. Statins do not interfere with exercise lowering the postprandial insulin that likely promotes fat oxidation. Last, statins do not restrict the rates of plasma incorporation or oxidation of the ingested glucose.

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. METHODS: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). FINDINGS: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. INTERPRETATION: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.