Bruno Lesourd

Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE* randomized trial

BACKGROUND Opinions differ over the exercise modalities that best limit cardiovascular risk (CVR) resulting from visceral obesity in individuals with metabolic syndrome (MetS). As little is known about the combined effects of resistance and endurance training at high volumes under sound nutritional conditions, we aimed to analyze the impact of various intensities of physical activity on visceral fat and CVR in individuals with MetS. METHODS 100 participants, aged 50-70 years, underwent a diet restriction (protein intake 1.2g/kg/day) with a high exercise volume (15-20 h/week). They were randomized to three training groups: moderate-resistance-moderate-endurance (re), high-resistance-moderate-endurance (Re), or moderate-resistance-high-endurance (rE). A one-year at-home follow-up (M12) commenced with a three-week residential program (Day 0 to Day 21). We measured the change in visceral fat and body composition by DXA, MetS parameters, fitness, the Framingham score and carotid-intima-media-thickness. RESULTS 78 participants completed the program. At D21, visceral fat loss was highest in Re (-18%, p<.0001) and higher in rE than re (-12% vs. -7%, p<.0001). Similarly, from M3, visceral fat decreased more in high-intensity-groups to reach a visceral fat loss of -21.5% (Re) and -21.1% (rE)>-13.0% (re) at M12 (p<.001). CVR, MetS parameters and fitness improved in all groups. Visceral fat loss correlated with changes in MetS parameters. CONCLUSION Increased intensity in high volume training is efficient in improving visceral fat loss and carotid-intima-media-thickness, and is realistic in community dwelling, moderately obese individuals. High-intensity-resistance training induced a faster visceral fat loss, and thus the potential of resistance training should not be undervalued (ClinicalTrials.gov number: NCT00917917).

Metabolic Syndrome Individuals With and Without Type 2 Diabetes Mellitus Present Generalized Vascular Dysfunction Cross-Sectional Study

Objectives— The first objective of this study was to demonstrate differences within endothelial-dependent and endothelial-independent vasoreactivity in macro- and microcirculation beds among patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2D) compared with healthy counterparts. The second objective was to determine relationships among the function of macro- and microvascular systems and abdominal adiposity, as well as inflammatory markers in the 3 groups. Approach and Results— Cross-sectional analyses of 53 patients with MetS without T2D and 25 with T2D, as well as aged 40 years and sex-matched healthy controls included microvascular (cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside), and macrovascular reactivity (flow-mediated dilation and nitrate-mediated dilation) along with anthropometric measures, plasma glucose, and insulin and inflammatory markers. Compared with controls, MetS participants showed depressed endothelial function of both micro- and macrocirculation beds. T2D in patients with MetS revealed an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared with MetS without T2D. Indices of micro- and macrocirculation were predominantly inversely related to abdominal fat and inflammatory markers. Conclusions— MetS was associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Participants with diabetes mellitus demonstrated the most severe smooth muscle dysfunction. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in MetS.

Blood lipids and adipokines concentrations during a 6-month nutritional and physical activity intervention for metabolic syndrome treatment.

BackgroundTo report changes in body weight, total and central fat mass, metabolic, hormonal and inflammatory parameters in overweight people who participated in a six months weight loss intervention associating diet management and exercise.Subjects and MethodsFourteen subjects (10 M, 4 F, mean age 62.9 ± 6.9 years, BMI 30.4+/- 3.8 kg/m2) presenting the characteristics of the Metabolic Syndrome (MS) were included in the survey. They followed a three weeks (D0 to D20) cure in a medical establishment and a six months (D20 to M3 and M6) follow up at home. During the cure, they receive a balanced diet corresponding to 500 Kcal deficit vs their dayly energy expenditure (DEE) and they exercised 2 to 3 hours per day.At D0, D20, M3 and M6, body composition (lean mass, total and central fat mass) was analyzed with DEXA, blood pressure was taken and blood was collected to evaluate glycaemia, triglycerides, total, LDL and HDL cholesterol, insulin, leptin and adiponectin levels, CRP and pro-inflammatory interleukines IL1, IL.6 and TNFalpha.ResultsAll parameters listed above except the cytokine were improved at D20, so that 4 subjects among 14 still presented the MS. After returning to home, these parameters remained stable.ConclusionThe efficacy of therapeutic lifestyle modifications with education and exercise and diet was demonstrated, but the compliance to the new healthy lifestyle initiated during the cure was not optimal.

Multilevel Approach of a 1-Year Program of Dietary and Exercise Interventions on Bone Mineral Content and Density in Metabolic Syndrome--the RESOLVE Randomized Controlled Trial.

Background Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome (MetS). However, restrictive diets might induce bone loss. The nature of exercise and whether exercise with weight loss programs can protect against potential bone mass deficits remains unclear. Moreover, compliance is essential in intervention programs. Thus, we aimed to investigate the effects that modality and exercise compliance have on bone mineral content (BMC) and density (BMD). Methods We investigated 90 individuals with MetS who were recruited for the 1-year RESOLVE trial. Community-dwelling seniors with MetS were randomly assigned into three different modalities of exercise (intensive resistance, intensive endurance, moderate mixed) combined with a restrictive diet. They were compared to 44 healthy controls who did not undergo the intervention. Results This intensive lifestyle intervention (15–20 hours of training/week + restrictive diet) resulted in weight loss, body composition changes and health improvements. Baseline BMC and BMD for total body, lumbar spine and femoral neck did not differ between MetS groups and between MetS and controls. Despite changes over time, BMC or BMD did not differ between the three modalities of exercise and when compared with the controls. However, independent of exercise modality, compliant participants increased their BMC and BMD compared with their less compliant peers. Decreases in total body lean mass and negative energy balance significantly and independently contributed to decreases in lumbar spine BMC. Conclusion After the one year intervention, differences relating to exercise modalities were not evident. However, compliance with an intensive exercise program resulted in a significantly higher bone mass during energy restriction than non-compliance. Exercise is therefore beneficial to bone in the context of a weight loss program. Trial Registration ClinicalTrials.gov NCT00917917

Impact of a Lifestyle Program on Vascular Insulin Resistance in Metabolic Syndrome Subjects: The RESOLVE Study

CONTEXT AND OBJECTIVE Impaired insulin-dependent vasodilation might contribute to microvascular dysfunction of metabolic syndrome (MetS). The aims of this study were to assess the insulin vasoreactivity in MetS, and to evaluate the effects of a lifestyle program. DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Laser Doppler measurements were used to assess cutaneous blood flux (CBF) and flowmotion in response to iontophoresis of insulin and acetylcholine (ACh) in 38 MetS and 18 controls. Anthropometric, plasma insulin, glycemia, and inflammatory markers were measured. MetS subjects (n = 24) underwent a 6-month lifestyle intervention (M6) with a 3-week residential program (D21). RESULTS The absolute and relative peak insulin and ACh CBF were significantly higher in controls than in MetS subjects. Significant inverse correlations were found between peak insulin CBF and glycemia, insulin and glycated hemoglobin, active plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and IL-6. With respect to flowmotion, MetS subjects showed lower values in total spectrum CBF and in all its components (except respiratory one). At D21 and M6, peak insulin CBF increased and was no longer different from control values whereas peak ACh CBF did not change. From D21, all the different components and the total CBF spectrum became similar to the control values. The changes in peak insulin CBF and in endothelial component between M6 and baseline were inversely correlated with the change in CRP and PAI-1. CONCLUSIONS The local vasodilatory effects to insulin and its overall flowmotion are impaired in MetS subjects in relation to inflammation. The lifestyle intervention reversed this insulin-induced vascular dysfunction in parallel to decreased inflammation level.

Treatment of metabolic syndrome by combination of physical activity and diet needs an optimal protein intake: a randomized controlled trial.

BackgroundThe recommended dietary allowance (RDA) for protein intake has been set at 1.0-1.3 g/kg/day for senior. To date, no consensus exists on the lower threshold intake (LTI = RDA/1.3) for the protein intake (PI) needed in senior patients ongoing both combined caloric restriction and physical activity treatment for metabolic syndrome. Considering that age, caloric restriction and exercise are three increasing factors of protein need, this study was dedicated to determine the minimal PI in this situation, through the determination of albuminemia that is the blood marker of protein homeostasis.MethodsTwenty eight subjects (19 M, 9 F, 61.8 ± 6.5 years, BMI 33.4 ± 4.1 kg/m2) with metabolic syndrome completed a three-week residential programme (Day 0 to Day 21) controlled for nutrition (energy balance of −500 kcal/day) and physical activity (3.5 hours/day). Patients were randomly assigned in two groups: Normal-PI (NPI: 1.0 g/kg/day) and High-PI (HPI: 1.2 g/kg/day). Then, patients returned home and were followed for six months. Albuminemia was measured at D0, D21, D90 and D180.ResultsAt baseline, PI was spontaneously 1.0 g/kg/day for both groups. Albuminemia was 40.6 g/l for NPI and 40.8 g/l for HPI. A marginal protein under-nutrition appeared in NPI with a decreased albuminemia at D90 below 35 g/l (34.3 versus 41.5 g/l for HPI, p < 0.05), whereas albuminemia remained stable in HPI.ConclusionDuring the treatment based on restricted diet and exercise in senior people with metabolic syndrome, the lower threshold intake for protein must be set at 1.2 g/kg/day to maintain blood protein homeostasis.

Occult Nighttime Hypertension in Daytime Normotensive Older Patients With Obstructive Sleep Apnea

OBJECTIVES To assess nighttime blood pressure (BP), the dipping phenomenon and the relationships between nighttime BP, and polysomnography parameters in older patients with obstructive sleep apnea (OSA) who have been identified by their primary care physician as being normotensive during the daytime. DESIGN Cross-sectional study. SETTING University hospital-based geriatric sleep center. PARTICIPANTS Daytime normotensive, community-dwelling older adults, consecutively referred by their primary care physicians for suspicion of OSA. MEASUREMENTS Overnight polysomnography and 24-hour ambulatory blood pressure measurement (ABPM). Daytime hypertension defined as systolic BP ≥135 mm Hg and/or diastolic BP ≥85 mm Hg. Nighttime hypertension defined as systolic BP ≥120 mm Hg and/or diastolic BP ≥70 mm Hg. Dipper pattern characterized by nighttime fall of mean BP ≥10%. RESULTS Forty-five participants (30 OSA; 15 non-OSA) completed the study (76.9 ± 6.2 years old). ABPM indicated clinically significant nighttime systolic (132.5 ± 16.0) and diastolic (72.6 ± 9.4) hypertension in patients with OSA previously classified as daytime normotensives and found only a mild degree of nighttime systolic hypertension (123.7 ± 16.1) in patients without OSA (P = .105). A significant nondipping phenomenon was found in patients with OSA (-0.5 ± 7.4 vs 5.4 ± 6.4; P = .016). Nighttime mean BP (r = 0.301; P = .049) and dipping status (r = -0.478; P = .001) were correlated with apnea-hypopnea index. A significant correlation was found between systolic BP (r = 0.321; P = .035), diastolic BP (r = 0.373; P = .013), mean BP (r = 0.359; P = .018), and hypoxia (sleep time spend with SaO2 <90%). CONCLUSION Daytime normotensive older adults with OSA are at high risk for having occult nighttime hypertension. Thus, 24-hour ABPM may be appropriate for older patients with OSA whose clinical blood pressure does not display any daytime elevation.

Left ventricular myocardial dyssynchrony is already present in nondiabetic patients with metabolic syndrome.

The presence of left ventricular (LV) dyssynchrony in individuals with metabolic syndrome (MetS), a predictor of type 2 diabetes (T2D), lacks clarity. We compared LV dyssynchrony in MetS individuals with and without T2D, and healthy control subjects using speckle-tracking imaging echocardiography. Ninety-two MetS participants (64 without, 28 with T2D) and 40 control subjects underwent echocardiographic and clinical/biological analyses. LV-dyssynchrony in the longitudinal axis only was present in all MetS individuals, but was not further exacerbated by T2D. Strong associations were found with systemic inflammation, abdominal obesity, and LV mass. Investigations of myocardial dyssynchrony in the nondiabetic MetS stage might facilitate timely and more effective prevention.

Right ventricle free wall mechanics in metabolic syndrome without type-2 diabetes: effects of a 3-month lifestyle intervention program

BackgroundGrowing evidence demonstrates subtle left ventricular myocardial dysfunction in patients with metabolic syndrome (MetS), with central obesity, glucose intolerance and inflammation emerging as important contributors. Whether these results can be translated to the right ventricle (RV) is not yet fully elucidated. Furthermore, although lifestyle intervention favorably impacts MetS components and inflammatory biomarkers, its effect on RV myocardial function remains unknown today.MethodsThirty-nine MetS adults free of diabetes were enrolled in a three month lifestyle intervention program including diet and physical exercise, and compared with forty healthy controls. Blood biochemistry, echocardiography including tissue Doppler imaging (TDI), and vector velocity imaging of the RV free wall to assess global longitudinal strain (GLS) and strain rates (SR) were obtained at baseline and after the intervention.ResultsCompared with controls, MetS patients presented similar right atrial and RV morphology but reduced systolic (P = 0.04) and early diastolic (P = 0.02) velocities of the tricuspid annulus. They showed attenuated RV GLS (−21.4 ± 4.5vs-25.7 ± 4.9%, P < 0.001) as well as early diastolic (P = 0.003) and systolic (P < 0.001) SR. Multiple regression analyses revealed log PAI-1 active, (P < 0.001), log adiponectin, (P = 0.01), LV mass indexed (P = 0.004) and central fat (P = 0.03) as independent predictors of RV GLS (R2 = 0.46, P < 0.001). Biological markers of MetS and inflammation as well as RV GLS (−21.8 ± 3.8vs-24.3 ± 3.0%, P = 0.009) and systolic (P = 0.003) and early diastolic (P = 0.01) SR, but not TDI indexes, significantly improved after diet and exercise training, and vector velocity imaging data in MetS following the lifestyle intervention no longer differed from controls.ConclusionsMetS is associated with subtle impairments in both RV free wall diastolic and systolic myocardial function which could be partly related to central-obesity induced changes in pro- and anti-inflammatory cytokines and left ventricular remodeling. The favorable impact of healthy dieting and physical activity on RV free wall mechanics indicates that cellular and sub-cellular alterations responsible for the RV myocardial abnormalities are probably not permanent and modifiable throughout adequate interventional strategies.Trial registrationAmerican National Institutes of Health database NCT00917917.

Paradoxical dissociation between heart rate and heart rate variability following different modalities of exercise in individuals with metabolic syndrome: The RESOLVE study.

Aims To analyse the effects of different modalities of exercise training on heart rate variability (HRV) in individuals with metabolic syndrome (MetS). Methods and results Eighty MetS participants (aged 50–70 years) were housed and managed in an inpatient medical centre for 21 days, including weekends. Physical activity and food intake/diet were intensively monitored. Participants were randomly assigned into three training groups, differing only by intensity of exercise: moderate-endurance-moderate-resistance (re), high-resistance-moderate-endurance (Re), and moderate-resistance-high-endurance (rE). HRV was recorded before and after the intervention by 24-hour Holter electrocardiogram. Although mean 24-hour heart rate decreased more in Re than re (–11.6 ± 1.6 vs. –4.8 ± 2.1%; P = 0.010), low frequency/high frequency decreased more in re than Re (–20.4 ± 5.5% vs. + 20.4 ± 9.1%; P = 0.002) and rE (–20.4 ± 5.5% vs. –0.3 ± 11.1%; P = 0.003). Very low frequency increased more in Re than re (+121.2 ± 35.7 vs. 42.9 ± 11.3%; P = 0.004). For all HRV parameters, rE ranged between re and Re values. Low frequency/high frequency changes were linked with visceral fat loss only in re (coefficient 5.9, 95% CI 1.9–10.0; P = 0.004). By day 21, HRV parameters of MetS groups (heart rate –8.6 ± 1.0%, standard deviation of R-R intervals + 34.0 ± 6.6%, total power + 63.3 ± 11.1%; P < 0.001) became closer to values of 50 aged-matched healthy controls. Conclusions A 3-week residential programme with intensive volumes of physical activity (15–20 hours per week) enhanced HRV in individuals with MetS. Participants with moderate intensity of training had greater improvements in sympathovagal balance, whereas those with high intensity in resistance training had greater decreases in heart rate and greater increases in very low frequency. Modality-specific relationships were observed between enhanced HRV and visceral fat loss. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917917.