A 5-Week Guided Active Play Program Modulates Skin Microvascular Reactivity in Healthy Children.

PURPOSE: Children's poor levels of physical activity (PA) participation and early-onset vascular aging are identified as global health challenges. Children's guided activity play (GAP)-based PA programs have emerged as effective strategies to improve cardiovascular risk factors and health-related fitness. This study proposes to investigate whether GAP improves children's cutaneous microvascular reactivity and health-related fitness. METHODS: Children's (n = 18; 9.8 [1.5] y) PA during a 5-week (4 d/wk; 1 h/d) GAP program was assessed (accelerometry) with preassessments and postassessments for anthropometric, musculoskeletal fitness, blood pressure, estimated aerobic power, and cutaneous microvascular reactivity. RESULTS: PA averaged 556 (132) kcal·week-1 at 34.7% (7.5%) time at moderate to vigorous intensity. Resting heart rate (-9.5%) and diastolic blood pressure (-7.8%) were reduced without changes in health-related fitness indices. Cutaneous microvascular reactivity to sodium nitroprusside iontophoresis increased the average perfusion (+36.8%), average cutaneous vascular conductance (+30%), the area under the curve (+28.8%), and a faster rise phase (+40%) of perfusion (quadratic modeling; P ≤ .05). Chi-square and crosstabulation analysis revealed significant association between children's PA levels and sodium nitroprusside average perfusion levels, where children with PA levels ≥205.1 kcal.55 minute-1 were overrepresented in the medium/high levels of sodium nitroprusside perfusion. CONCLUSION: A 5-week GAP modified the microvascular reactivity in children without changes in body mass, musculoskeletal fitness, or estimated aerobic power.

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.

Study protocol for a pragmatic cluster randomized controlled trial to improve dietary diversity and physical fitness among older people who live at home (the "ALAPAGE study").

BACKGROUND: Diet and physical activity are key components of healthy aging. Current interventions that promote healthy eating and physical activity among the elderly have limitations and evidence of French interventions' effectiveness is lacking. We aim to assess (i) the effectiveness of a combined diet/physical activity intervention (the "ALAPAGE" program) on older peoples' eating behaviors, physical activity and fitness levels, quality of life, and feelings of loneliness; (ii) the intervention's process and (iii) its cost effectiveness. METHODS: We performed a pragmatic cluster randomized controlled trial with two parallel arms (2:1 ratio) among people ≥60 years old who live at home in southeastern France. A cluster consists of 10 people participating in a "workshop" (i.e., a collective intervention conducted at a local organization). We aim to include 45 workshops randomized into two groups: the intervention group (including 30 workshops) in the ALAPAGE program; and the waiting-list control group (including 15 workshops). Participants (expected total sample size: 450) will be recruited through both local organizations' usual practices and an innovative active recruitment strategy that targets hard-to-reach people. We developed the ALAPAGE program based on existing workshops, combining a participatory and a theory-based approach. It includes a 7-week period with weekly collective sessions supported by a dietician and/or an adapted physical activity professional, followed by a 12-week period of post-session activities without professional supervision. Primary outcomes are dietary diversity (calculated using two 24-hour diet recalls and one Food Frequency Questionnaire) and lower-limb muscle strength (assessed by the 30-second chair stand test from the Senior Fitness Test battery). Secondary outcomes include consumption frequencies of main food groups and water/hot drinks, other physical fitness measures, overall level of physical activity, quality of life, and feelings of loneliness. Outcomes are assessed before the intervention, at 6 weeks and 3 months later. The process evaluation assesses the fidelity, dose, and reach of the intervention as its causal mechanisms (quantitative and qualitative data). DISCUSSION: This study aims to improve healthy aging while limiting social inequalities. We developed and evaluated the ALAPAGE program in partnership with major healthy aging organizations, providing a unique opportunity to expand its reach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05140330 , December 1, 2021. PROTOCOL VERSION: Version 3.0 (November 5, 2021).

Vitamin D Supplementation on Carotid Remodeling and Stiffness in Obese Adolescents.

Obesity is associated with vitamin D (VD) deficiency and arterial stiffness. This randomized control trial assessed the effects of VD supplementation during a weight-loss program on carotid intima-media thickness (IMT) and carotid compliance in obese adolescents. Participants were randomly assigned to receive either a 12-week lifestyle program with VD supplementation (n = 13), a lifestyle program without VD supplementation (n = 13) or a control group composed of normal-weight adolescents (n = 18). Serum total and free 25-hydroxyvitamin D (25(OH)D), IMT and carotid compliance were measured before and after the trial. Insufficiency in 25(OH)D concentration was found in 73% of obese participants compared to 22% among controls. Obese adolescents had lower free 25(OH)D and displayed higher IMT but lower carotid compliance than controls. Free 25(OH)D and IMT were negatively correlated in adolescents displaying VD insufficiency at baseline. After three months, total and free 25(OH)D increased in both groups. The changes of IMT and carotid compliance were similar between groups. The changes in IMT were correlated with the changes in total 25(OH)D in obese adolescents with VD insufficiency at baseline (r = -0.59, p = 0.03). While the lifestyle program with VD supplementation did not affect carotid compliance, IMT reduction was improved in obese adolescents.

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.

Effect of vitamin D supplementation on microvascular reactivity in obese adolescents: A randomized controlled trial.

BACKGROUND AND AIM: Childhood obesity is associated with vitamin D (VD) deficiency and vascular dysfunction. Considering evidence indicates that VD may improve vascular function, this study, for the first time, assessed the effect of VD supplementation on microvascular reactivity in obese adolescents (OA). METHODS AND RESULTS: This randomized controlled trial included 26 OA, receiving fruit juice with (n = 13) or without VD (4000 IU/d; n = 13) over a 3-month lifestyle program, as well as 23 normal-weight adolescents (controls). The primary outcome was the pre-to-post-program change in microvascular reactivity determined by laser speckle contrast imaging with acetylcholine and sodium nitroprusside iontophoresis. Changes in 25 hydroxyvitamin D (25(OH)D), flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), insulin resistance (HOMA-IR) and inflammatory markers (C-reactive protein [CRP]) were monitored. At inclusion, in comparison to controls, OA exhibited lower total and free 25(OH)D, impaired microvascular responses, and impaired FMD, but similar NMD. After the lifestyle program, total and free 25(OH)D increased in all OA, with a greater increase in those receiving VD supplements. HOMA-IR and CRP decreased in all OA. Neither FMD nor NMD were altered in either group. Endothelium-dependent microvascular reactivity only increased in the VD-supplemented group, reaching values comparable to that of controls. Similar results were found when analyzing only OA with a VD deficiency at baseline. CONCLUSION: VD supplementation during a lifestyle program attenuated microvascular dysfunction in OA without altering macrovascular function. REGISTRATION NUMBER FOR CLINICAL TRIAL: NCT02400151.

Concomitant Peripheral Neuropathy and Type 2 Diabetes Impairs Postexercise Cutaneous Perfusion and Flowmotion.

CONTEXT: Type 2 diabetes and peripheral neuropathy exhibit microvascular dysfunction at rest. However, data regarding their microvascular perfusion during exercise remain scarce. OBJECTIVE: This study investigated changes in microvascular perfusion during postexercise recovery in those with type 2 diabetes, with or without peripheral neuropathy, as well as in healthy controls and those with obesity. METHODS: Skin blood perfusion was assessed in each group using laser Doppler flowmetry (LDF) and laser speckle contrast imaging before and immediately after a 6-minute walking test. LDF recordings underwent wavelet transformation to allow specific control mechanisms of blood perfusion to be studied (eg, endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory, and cardiac mechanisms). RESULTS: Skin blood perfusion increased after exercise in all groups (22.3 ±â€…28.1% with laser speckle contrast imaging and 22.1 ±â€…52.5% with LDF). Throughout postexercise recovery, the decrease was blunted in those with subclinical peripheral neuropathy and confirmed peripheral neuropathy when compared to the other 3 groups. After exercise, total spectral power increased in all groups. The relative contributions of each endothelial band was lower in those with confirmed peripheral neuropathy than in the healthy controls and those with obesity (nitric oxide-dependent function: 23.6 ±â€…8.9% vs 35.5 ±â€…5.8% and 29.3 ±â€…8.8%, respectively; nitric oxide-independent function: 49.1 ±â€…23.7% vs 53.3 ±â€…10.4% and 64.6 ±â€…11.4%, respectively). The neurogenic contribution decreased less in those with confirmed peripheral neuropathy and in those with type 2 diabetes alone, compared to those with subclinical peripheral neuropathy and those with obesity (-14.5 ±â€…9.9% and -12.2 ±â€…6.1% vs -26.5 ±â€…4.7% and -21.7 ±â€…9.4%, respectively). CONCLUSION: Peripheral neuropathy, whatever the stage, altered the microvascular response to exercise via impaired endothelial and neurogenic mechanisms.

Mechanisms of Venoarteriolar Reflex in Type 2 Diabetes with or without Peripheral Neuropathy.

The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.

Changes in the profile of circulating HDL subfractions in severe obese adolescents following a weight reduction program.

BACKGROUND AND AIMS: Epidemiological studies show that obese adolescents are candidates to suffer cardiovascular pathologies in adulthood. In order to detect subfractions with a diagnostic value for future cardiovascular disorders, we analyzed the complete lipoprotein profile of severely obese adolescents. METHODS AND RESULTS: Twenty-eight obese adolescents free from comorbidities were admitted into a weight reduction program. Anthropometric parameters were monitored. The circulating lipoproteins and glycemia were measured at the beginning and at the end of the study by conventional blood analysis as well as by using lipoprotein electrophoresis. Twenty-one puberty-matched normal-weight adolescents were recruited as controls. After 4 months, participants improved anthropometric parameters. Blood analysis indicated that circulating lipoproteins were in the healthy range during intervention. Nevertheless, results obtained from lipoprotein electrophoresis showed a significant increase in the large high-density lipoprotein subfraction in the obese population at the end of intervention, but significantly lower than normal-weight counterparts. In addition, intermediate- and low-density lipoprotein subfractions were in the healthy range in controls and in obese adolescents during intervention. CONCLUSIONS: Altogether, it seems that the obese adolescents with no comorbidities do not develop a clear dyslipidemia. However, low values of large high-density lipoprotein subfractions could be considered as candidate predictors to develop cardiovascular disease in the future. For this reason, diet and exercise are key tools to fight against this pathology. REGISTRATION NUMBER FOR CLINICAL TRIALS: ISRCTN99414527.

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.

Glutathione-dependent enzyme activities of peripheral blood mononuclear cells decrease during the winter season compared with the summer in normal-weight and severely obese adolescents.

Oxidative stress-related inflammation is known to play a vital role in obesity-associated cardiovascular disease, contributing to the early stages of the pathology as well as during its development. Therefore, it is of great interest to understand how obesity-induced stress modulates antioxidant enzyme activity during puberty. To this end, 27 severely obese adolescents (body mass index > 30, z-score > 3.7) were recruited from a paediatric weight management centre. Eighteen were recruited during the summer and nine in the winter. All underwent a 4-month weight loss programme consisting in diet and physical activity. Twenty normal-weight age-matched adolescents were recruited from the same geographical area to serve as controls. Blood samples were extracted, and antioxidant enzyme activities were determined in peripheral blood mononuclear cells (PBMCs) and erythrocytes. The enzymes studied included catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Severely obese adolescents presented lower PBMC-glutathione reductase activity than their corresponding normal-weight counterparts. In addition, glutathione-dependent activities tended to be lower in both groups during the winter compared with summer. These changes coincided with differences in circulating vitamin D levels. Results may suggest that season-dependent factors such as vitamin D could affect glutathione-dependent activities in severely obese as well as in normal-weight adolescents.

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.

Increased Prevalence of Type 2 Diabetes-Related Complications in Combined Type 2 Diabetes and Sickle Cell Trait.

OBJECTIVE: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. RESEARCH DESIGN AND METHODS: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. RESULTS: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. CONCLUSIONS: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.

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.

Effects of Exercise Intensity on Microvascular Function in Obese Adolescents.

The optimal exercise modality for the improvement of health-related parameters and microvascular function in obese adolescents is not yet fully understood. Therefore, this study aimed to 1) compare the microvascular phenotype of obese and normal-weight adolescents; and 2) to determine the effects of a lifestyle intervention including three months of moderate continuous training (MCT) or high-intensity interval training (HIIT) on health-related parameters and microvascular function in 29 obese adolescents. Body composition, metabolic profile, aerobic fitness and cutaneous blood flow, measured using laser Doppler flowmetry at rest and during post-occlusive reactive hyperemia, were assessed prior to and following lifestyle intervention. Sixteen normal-weight adolescents were included as reference controls for baseline microvascular parameters. At baseline, obese adolescents had higher peak blood flow, peak vascular conductance and area under the curve for post-occlusive reactive hyperemia than normal-weight adolescents. Conversely, peak blood flow, peak vascular conductance and area under the curve data remained unchanged after MCT and HIIT without intergroup differences. However, the peak/basal blood flow ratio decreased in both MCT and HIIT groups without any interaction between groups due to basal CBF increase (tendency p=0.074). Exercise training, whatever the modality, does not improve peak microcirculatory function.

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.

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.

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.

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.