Cardiorespiratory Fitness and Bone Turnover Markers in Adults With Metabolic Syndrome: The Mediator Role of Inflammation.

The relationship between inflammatory markers and bone turnover in adults is well known, and a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5 ± 5.0 years, 62.7% women) were included in the analysis. CRF was measured by the 6-min walking test. Serum interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP), and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy X-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers, and bone turnover markers, controlling for sex, lean mass, and fat mass. Boot-strapped mediation procedures were performed, and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r = .228, p = .044) and osteocalcin levels (r = .296, p = .009). Furthermore, CRF was positively correlated with IL-1ß levels (r = .340, p = .002) and negatively correlated with hsCRP levels (r = -.335, p = .003), whereas IL-1ß levels were positively correlated with P1NP levels (r = .245, p = .030), and hsCRP levels were negatively correlated with P1NP levels (r = -.319, p = .004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (percentage of mediation = 39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population.

Regional myocardial function abnormalities are associated with macro- and microcirculation dysfunction in the metabolic syndrome: the RESOLVE study.

Abnormalities in myocardial and vascular function have been reported in the metabolic syndrome (MetS), but whether these alterations are related remains poorly documented. Our aim was accordingly to investigate interrelationships between macro- and microcirculatory vasoreactivity and left ventricular (LV) myocardial function in MetS patients. Eighty-eight MetS individuals and 44 age- and gender-matched healthy controls were enrolled. LV global longitudinal strain (GLS) was measured using Vector Velocity Imaging. Endothelial-dependent and independent reactivity in macro- and microcirculatory territories was established using flow-mediated dilation and nitrate-mediated dilation of the brachial artery and cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside, respectively. Carotid intima-media thickness (cIMT) was measured according to the Mannheim consensus. Compared to controls, MetS patients presented with reduced GLS (p < 0.001) increased cIMT and impaired (p < 0.001) endothelial and smooth muscle function of the brachial artery and the forearm skin microcirculation. Highly significant relationships (p < 0.01) were noticed between GLS and vascular outcomes. In addition, cIMT (ß = 0.21, p = 0.024) and microcirculatory endothelium-dependent reactivity (ß = - 0.20, p = 0.035) were identified as independent predictors of GLS. In MetS, abnormalities in myocardial function and endothelial as well as smooth muscle function of small and large arteries co-exist and are closely associated. This study supports a role for microvascular dysfunction in the pathogenesis of LV myocardial dysfunction.

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.

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

BACKGROUND: Growing 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. METHODS: Thirty-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. RESULTS: Compared 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 ± 4.5 vs -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 ± 3.8 vs -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. CONCLUSIONS: MetS 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 REGISTRATION: American National Institutes of Health database NCT00917917.

Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet - the RESOLVE trial.

BACKGROUND: We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis. METHODS: 100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint® electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured. RESULTS: 78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Using a generalized estimating equations model, none of the subfractions of lipoproteins nor apolipoproteins were linked to CIMT. CONCLUSIONS: Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions. TRIAL REGISTRATION: NCT00917917.

Effect of different modalities of exercise on Fatty Liver Index in patients with metabolic syndrome: The RESOLVE randomized trial.

INTRODUCTION: Metabolic associated liver disease (MASLD) is the most common liver disease in the world especially in people with metabolic syndrome. First-line treatments mainly consist in lifestyle modifications for these populations. The main objective of this study is to assess the effect of a short intervention program with different exercise modalities on Fatty Liver Index (FLI) in patients with metabolic syndrome. METHODS: 85 patients (40 men, 45 women) with metabolic syndrome and liver steatosis were randomized in 3 groups for a 3 weeks residential program: Re group-high-resistance-moderate-endurance; rE group-moderate-resistance with high-endurance and re group-moderate-resistance with moderate-endurance. Patients also followed a negative energy balance of 500 kcal/day. Then, a follow-up of 1 year with interviews with dieticians and exercise physicians to maintain lifestyle modification was performed. Anthropometric, cardiometabolic and hepatic outcomes were performed at baseline, at the end of the 3-week residential program, 3 months, 6 months and 12 months after baseline. RESULTS: This study demonstrated that all three training programs significantly improve FLI and that this effect was lasting among the follow-up (p < 0.001). More specifically, the Re group exhibited a more pronounced decrease in FLI compared with re (p < 0.05). Finally, the decrease in FLI was associated with improvement in anthropometric and cardiometabolic outcomes at 3-weeks (p < 0.001) and 3-months (p < 0.01). CONCLUSION: Short duration program is effective to improve FLI and cardiometabolic parameters in MASLD patients. Encourage to increase physical activity even for a short duration is relevant in this population.

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

BACKGROUND: The 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. METHODS: Twenty 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. RESULTS: At 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. CONCLUSION: During 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.

Non-invasive biomarkers of non-alcoholic fatty liver disease in patients with Metabolic Syndrome: insights from the RESOLVE study.

BACKGROUND: The aim of the present study was to evaluate i) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from MS and ii) the association of FLI, HSI and LFS with the cardiometabolic risks. METHODS: A total of 91 patients with MS (MS; 39 men, 52 women) and 44 age matched healthy subjects (Control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis. RESULTS: Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (p<0,05). Also, FLI and LFS were positively associated with MetsScore (p<0.01 and p<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (p<0,001). CONCLUSIONS: FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

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

BACKGROUND: To 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 METHODS: Fourteen 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 daily 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. RESULTS: All 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. CONCLUSION: The 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.

Dietary Fibres and the Management of Obesity and Metabolic Syndrome: The RESOLVE Study.

OBJECTIVES: This study was performed to evaluate the long-term maintenance of nutritional changes promoted during an intensive initial intervention to induce body weight loss. The ability of these changes to predict long-term health outcomes was also examined. METHODS: Nutritional variables, body composition, and metabolic markers collected in the RESOLVE project were analyzed before and after a 3-week intensive diet-exercise intervention (Phase 1), and during a subsequent supervision under free living conditions, of 12 months (Phase 2). RESULTS: As expected, the macronutrient composition of the diet was modified to promote a negative energy balance during Phase 1. The decrease in carbohydrates imposed during this phase was maintained during Phase 2 whereas the increase in protein intake returned to baseline values at the end of the program. Dietary fiber intake was almost doubled during Phase 1 and remained significantly greater than baseline values throughout Phase 2. Moreover, fiber intake was the only nutritional variable that systematically and significantly predicted variations of health outcomes in the study. CONCLUSION: The adequacy of dietary fiber intake should be a matter of primary consideration in diet-based weight reduction programs.

Long-term effects of high-intensity resistance and endurance exercise on plasma leptin and ghrelin in overweight individuals: the RESOLVE Study.

The objective of this study was to evaluate the effects of high-intensity resistance and endurance exercise on body composition and plasma leptin and ghrelin concentrations in overweight individuals. One hundred participants were randomly assigned to 3 exercise interventions: high-resistance-low-aerobic exercise (Re), low-resistance-high-aerobic exercise (rE), low-resistance-low-aerobic exercise (re). Interventions began with 3 weeks of residential supervision (phase 1) after which participants had to manage the physical activity programs individually (phase 2). Body composition and plasma variables were measured at baseline and after phase 1 as well as after 3, 6, and 12 months. Significant decreases in body weight and fat were observed after phase 1 (p < 0.001) and continued at a lower rate for up to 3 months and then remained stable for the rest of the protocol. Once a body weight plateau was reached, body fat loss after the Re and rE conditions exceeded the fat loss observed in the re condition by 1.5-2 kg (p < 0.05). Leptin was significantly decreased after day 21 and month 3 (p < 0.001) and remained stable for the rest of the study. Ghrelin was significantly increased after day 21 and month 3 (p < 0.001) and returned to a level comparable to baseline between month 6 and 12 when body weight and fat had reached a plateau. In conclusion, this study reinforces the idea that an increase in exercise intensity may accentuate body fat loss before the occurrence of a body weight plateau. Resistance to further fat loss was accompanied by a decrease in plasma leptin and an increase in plasma ghrelin.

Different modalities of exercise improve macrovascular function but not microvascular function in metabolic syndrome: The RESOLVE randomized trial.

OBJECTIVE: To determine which modality of exercise program (endurance and/or resistance dominance) is the most effective for improving vascular function in the micro- and macrocirculation in metabolic syndrome (MetS). METHODS: Sixty-two MetS patients were enrolled in a 6-month lifestyle intervention program based on diet and exercise training. Each participant was randomly assigned to one of 3 groups categorized by exercise modality (e.g. high-intensity resistance or endurance training, or combined moderate-intensity). Measurements of anthropometrics, biological blood markers, physical fitness and vascular function were performed at baseline, at the end of the 3-week residential program, and at 3 and 6 months after baseline. Brachial artery flow-mediated dilation (FMD) and the response to sublingual nitrate were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated using laser Doppler flowmetry in conjunction with iontophoresis of acetylcholine and sodium nitroprusside. RESULTS: Regardless of the training program, FMD significantly increased from baseline to 3 weeks in all groups with no further changes at 3 and 6 months. Changes in central fat, diastolic blood pressure, triglycerides, interleukin-6 and physical fitness were independent predictors of increased FMD. Nitrate-mediated dilation increased from baseline to 3 months and then remained unchanged up to 6 months. Endothelium-dependent and endothelium-independent function of the skin microcirculation did not change significantly in all groups. CONCLUSIONS: In MetS patients, exercise training, regardless of its endurance or resistance dominance, is able to improve vascular function in large vessels only. Lifestyle intervention programs including exercise training must be encouraged in those with MetS. 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.

Long-term cost reduction of routine medications following a residential programme combining physical activity and nutrition in the treatment of type 2 diabetes: a prospective cohort study.

OBJECTIVES: To demonstrate that lifestyle modifications will reduce the cost of routine medications in individuals with type 2 diabetes (T2D), through a mechanism involving glycaemic control. DESIGN: A within-trial cost-medication analysis with a 1-year time horizon. SETTING: Controlled environment within the spa resort of Chatel-Guyon, France. PARTICIPANTS: Twenty-nine participants (aged 50-70 years) with T2D. INTERVENTIONS: A 1-year follow-up intervention, beginning with a 3-week residential programme combining high exercise volume (15-20 hours/week), restrictive diet (-500 kcal/day) and education. Participants continued their routine medication, independently managed by their general practitioner. MAIN OUTCOME MEASURES: Number of medications, number of pills, cost of medications and health-related outcomes. RESULTS: Twenty-six participants completed the 1-year intervention. At 1 year, 14 patients out of 26 (54%) stopped/decreased their medications whereas only 5 (19%) increased or introduced new drugs (χ2=6.3, p=0.02). The number of pills per day decreased by 1.3±0.3 at 12 months (p<0.001). The annual cost of medications for T2D were lower at 1 year (€135.1±43.9) versus baseline (€212.6±35.8) (p=0.03). The regression coefficients on costs of routine medication were 0.507 (95% CI 0.056 to 0.959, p=0.027) for HbA1c and 0.156 (95% CI -0.010 to 0.322, p=0.06) for blood glucose levels. Diabetics patients with HbA1c >6.5% in the highest (last) quartile doubled their routine medication costs (66% vs 33%, p=0.037). CONCLUSIONS: Individuals with T2D reduced routine medication costs following a long-term lifestyle intervention that started with a 3-week residential programme. Combining high exercise volume, restrictive diet and education effectively supported the health of T2D. The main factor explaining reduced medication costs was better glycaemic control, independent of weight changes. Despite limitations precluding generalisability, cost-effective results of reduced medication should contribute to the evidence base required to promote lifestyle interventions for individuals with T2D. TRIAL REGISTRATION NUMBER: NCT00917917; Post-results.

Effects of lifestyle intervention on left ventricular regional myocardial function in metabolic syndrome patients from the RESOLVE randomized trial.

AIMS: The purpose of our study was to determine the effect of lifestyle intervention on left ventricular (LV) regional myocardial function in patients with metabolic syndrome (MetS) and investigate the relationships of the changes in myocardial function to changes in epicardial adipose tissue (EAT), inflammatory profile and MetS components. METHODS: Eighty-seven MetS patients were enrolled in a 6month lifestyle intervention program based on dietary management and increased physical activity, and compared with 44 aged and sex-matched healthy controls. MetS individuals were allocated to different groups randomized (computer-generated randomization) on exercise modalities (high-intensity dominant resistance or aerobic training, and moderate-intensity of both modes). EAT was measured by transthoracic echocardiography and LV longitudinal strains and strain rates were obtained using vector velocity imaging. Blood chemistry allowed assessments of adipocytokines (TNF-α: tumor necrosis factor α, PAI active: active plasminogen activator inhibitor-1 and adiponectin) and glucose tolerance markers. RESULTS: Regardless of exercise training modalities, lifestyle intervention improved significantly LV strains and strain rates (p<0.001) as well as metabolic and inflammatory profiles. Stepwise multiple regression analyses revealed EAT (ß=0.73, p<0.01), log adiponectin (ß=-0.13, p<0.05) and log TNF-α (ß=0.15, p<0.05) as independent predictors of LV longitudinal strain (R(2)=0.74, p<0.001) while myocardial function improvement consecutive to lifestyle intervention was explained by EAT changes only (R(2)=0.54, p<0.001). CONCLUSION: The mechanisms through which regional myocardial function is impaired in MetS and improved consecutive to intervention involved EAT, possibly via paracrine effects of adipocytokines. EAT should be considered as a future therapeutic target of interest in the treatment of metabolic-related cardiac diseases.

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.

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.

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.

Myocardial deformation and twist mechanics in adults with metabolic syndrome: impact of cumulative metabolic burden.

OBJECTIVE: The aim of the study is to characterize left ventricular (LV) myocardial mechanics in adults with metabolic syndrome (MetS), and elucidate the effects of multiple risk-factors on myocardial function using speckle tracking echocardiography (STE); a more sensitive method than conventional echocardiography for detecting subclinical myocardial dysfunction. DESIGN AND METHODS: Cross-sectional analyses of 92 adults (50-70 years) with MetS, and 50 healthy controls included conventional echocardiography, blood biochemistry, and STE-derived myocardial longitudinal, circumferential, and twist mechanics. RESULTS: Using conventional measures, MetS participants revealed LV hypertrophy and reduced diastolic function compared with controls, while systolic function was preserved. From STE, MetS participants showed attenuated longitudinal strain (-16.8% ± 2.8% vs. -20.6% ± 2.7%), and both diastolic (1.1 ± 0.2 vs. 1.4 ± 0.3 s s(-1) ) and systolic (-1.0 ± 0.1 vs. -1.2 ± 0.2 s s(-1) ) strain rate (SR). Circumferential strain, SR, and twist mechanics did not differ. Participants with the highest number of MetS factors or diabetes demonstrated the greatest reduction in longitudinal strain and SR. Abdominal obesity, TNF-α, HbA1c , and systolic dyssynchrony explained 48% of impairment in longitudinal strain. CONCLUSIONS: Impaired longitudinal myocardial diastolic and systolic function, but preserved circumferential function and twist mechanics were found in MetS participants, indicative of altered subendocardial function. This dysfunction was best predicted by abdominal obesity, inflammation, glucose-intolerance, and systolic dyssynchrony.

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).