Short-Term Resistance Training Attenuates Cardiac Autonomic Dysfunction in Obese Adolescents.

PURPOSE: Cardiac autonomic dysfunction (CADysf) in children is often associated to obesity and may be attenuated by physical activity. In this study, we investigated the effects of resistance training (RT) upon CADysf assessed by heart rate variability (HRV) in obese adolescents. METHOD: Volunteers were assigned into groups according to standard deviation scores for body mass index (z-BMI) and percentile for age and sex: obese (OB; z-BMI from 2 to 3 and ≥ 95th percentile, n = 24) and normal weight controls (CG; z-BMI from -2-1 and < 85th percentile, n = 20). OB performed isolated RT during 12 weeks [3 sets of 6-10reps with 70-85% 10RM]. Waist circumference, systolic/diastolic blood pressures (SBP/DBP), lipids, and HRV were assessed at baseline. Only OB underwent postintervention assessments. RESULTS: At baseline, SBP (122.4 ± 9.1 vs. 109.7 ± 11.5 mmHg, p < .001) and DBP (76.1 ± 7.1 vs. 65.3 ± 5.9 mmHg, p < .001) were higher, while parasympathetic HRV indexes were lower (p < .05) in OB compared with CG. After RT, waist circumference (3%, p < .001) and SBP (10%, p < .001) reduced in OB. Parasympathetic indexes of HRV increased in OB (SDNN: 25%, p = .03; rMSSD: 48%, p = .0006; pNN50: 67%, p = .001; total power: 54%, p = .01; HF: 101%, p = .001) and baseline differences between groups for sympathetic and parasympathetic activities were no longer observed after RT. CONCLUSION: RT attenuated CAdyfs and BP in obese adolescents, by increasing parasympathetic activity and decreasing sympatho-vagal balance.

Relationships between emerging cardiovascular risk factors, z-BMI, waist circumference and body adiposity index (BAI) on adolescents.

OBJECTIVE: The body adiposity index (BAI) has been recently proposed as an alternative index to body mass index (BMI) and waist circumference (WC) to evaluate adiposity in adults, with special focus on its ability to discriminate gender specificities on adiposity. Endothelial dysfunction, circulating endothelial cells (CECs), endothelin-1 and adipocytokines are all related to atherosclerosis and nowadays considered as markers of emerging cardiovascular (CV) risk. This study aimed to determine in normal weight and obese adolescents which measures of body composition (BAI and z-BMI) or distribution (WC) correlate better with emerging CV risk markers. PATIENTS: Forty adolescents were selected according to BMI: normal weight (n = 20; 7 girls/13 boys, 14·7 ± 1·4 years, 53·4 ± 6·0 kg, z-BMI 0·6 ± 0·1) and obese ones (n = 20; 13 girls/7 boys, 14·1± 1·0 years, 86·7 ± 11·5 kg, z-BMI 2·7 ± 0·4). MEASUREMENTS: Body fat and fat mass were measured by dual-energy X-ray absorptiometry (DXA). Non-nutritive skin microvascular reactivity was evaluated by laser Doppler flowmetry with iontophoretic release of vasoactive drugs. Activated CECs were assessed by flow cytometric analysis. RESULTS: In adolescents, the measurement of % fat by DXA showed high correlation with BAI (ρ = 0·75, P < 0·0001), z-BMI (r = 0·84, P < 0·0001) and WC (r = 0·83, P < 0·0001). Endothelin-1 and activated CECs did not correlate with any anthropometric measures while adipocytokines expressed variable associations among them. Endothelium-dependent vasodilation showed higher correlation with BAI (r = -0·51, P < 0·0001) compared to z-BMI (r = -0·40, P < 0·001) or WC (r = -0·45, P < 0·001), specially on females. CONCLUSIONS: BAI was associated with emerging CV risk markers in adolescents but further research is needed to evaluate its potential in clinical and epidemiological sets.

Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach.

BACKGROUND: We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. METHODS: Data from 189 female subjects (34.0 ± 15.5 years, 30.5 ± 7.1 kg/m2), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). RESULTS: A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity. CONCLUSIONS: In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

Waist circumference leads to prolonged microvascular reactive hyperemia response in young overweight/obese women.

OBJECTIVES: Previous data in our laboratory have shown microvascular dysfunction in normoglycaemic subjects with metabolic syndrome (MS). In a step further, we have investigated which clinical parameters related or not to MS would elicit microvascular dysfunction and the need of diagnosing MS for the establishment of microcirculatory impairment in overweight/obese women. METHODS: Nineteen lean [23.6±3.1years, body mass index (BMI) 21.9±1.8kg/m(2)] and 59 overweight/obese [24.6±3.7years; BMI 34.4±5.9kg/m(2)] sedentary non-smoking women, divided in overweight/obese without (MS negative, n=36) and obese with MS (MS positive, n=23) were evaluated. Blood biochemistry, HOMA-IR index and anthropometric variables were determined. Morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak and time (TRBCV(max)) to reach it during post-occlusive reactive hyperemia after 1min ischemia] microcirculatory variables were examined by nailfold videocapillaroscopy. RESULTS: Compared to controls, overweight/obese MS negative and obese MS positive presented longer TRBCV(max); the presence of two MS components was sufficient to prolong it and the MS diagnosis did not add any significant impairment to the microcirculation. Among clinical parameters investigated, a direct relationship between TRBCV(max) and waist circumference and insulin concentrations was found. CONCLUSION: Our results have shown that microvascular dysfunction is independent of metabolic syndrome diagnosis and could be predicted by the waist circumference on young overweight/obese women, reinforcing the relationship between obesity-related microvascular/metabolic disturbances.

Treating prediabetes: why and how should we do it?

Prediabetes is the subclinical impairment in fasting plasma glucose, impaired glucose tolerance or both. The degree of impairment is between euglycemia and the hyperglycemia of type 2 diabetes (T2DM). Prediabetes is not considered benign, because it is a risk factor for T2DM but is also associated with micro and macrovascular complications. Lifestyle interventions including diet and exercise are first-line treatments. Medications can also play a role, as randomized controlled trials of biguanides (metformin) alpha-glucosidase inhibitors (Acarbose), inhibitors of pancreatic lipase (Orlistat), PPAR-gamma agonists (Rosiglitazone, Pioglitazone), meglitinides (Nateglinide) and GLP-1 receptor agonists (Liraglutide) have all shown benefits. Bariatric surgery is another efficacious means of preventing T2DM in patients with prediabetes and obesity. Prediabetes in its various guises is a risk factor for the future development T2DM and diabetic complications. Importantly the prediabetic state is amenable to interventions that prevent/delay transition to overt T2DM. Knowledge gaps exist regarding how best to make prognostication highly sensitive and specific as to which patient will develop T2DM. Moreover, understanding of phenotype specific pathophysiology may add value to funding appropriate interventions for patients with prediabetes. Management of patients with prediabetes should be individualized based on the algorithms that predict phenotype specific risk and allow for the use of phenotype tailored interventions.

Short-term effects of low-dose estradiol on endothelial function and blood viscosity in nondiabetic postmenopausal overweight women: a double-blind, placebo-controlled study.

OBJECTIVE: The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women. METHODS: Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means ±â€ŠSD or medians [first to third quartiles]. RESULTS: Participants were aged 51.8 ±â€Š2.3 years with a body mass index of 31.5 ±â€Š2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32-22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293-0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 ±â€Š0.12 vs 3.76 ±â€Š0.22 mPa.s; P < 0.01). CONCLUSIONS: Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo.

Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow.

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow.

Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial.

BACKGROUND: Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents. METHODS: Obese female adolescents (n = 17), 15.4 ± 2.0 years and BMI of 35.6 ± 3.3 kg/m2, were randomized 1:1 in two groups with the diet supplemented either with Brazil nuts [BNG, n = 08, 15-25 g/day (equivalent to 3 to 5 units/day)] or placebo [PG (lactose), n = 09, one capsule/day] and followed for 16 weeks. Anthropometry, metabolic-lipid profiles, oxidative stress and morphological (capillary diameters) and functional [functional capillary density, red blood cell velocity (RBCV) at baseline and peak (RBCVmax) and time (TRBCVmax) to reach it during post-occlusive reactive hyperemia, after 1 min arterial occlusion] microvascular variables were assessed by nailfold videocapillaroscopy at baseline (T0) and after intervention (T1). RESULTS: T0 characteristics were similar between groups. At T1, BNG (intra-group variation) had increased selenium levels (p = 0.02), RBCV (p = 0.03) and RBCVmax (p = 0.03) and reduced total (TC) (p = 0.02) and LDL-cholesterol (p = 0.02). Compared to PG, Brazil nuts intake reduced TC (p = 0.003), triglycerides (p = 0.05) and LDL-ox (p = 0.02) and increased RBCV (p = 0.03). CONCLUSION: Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances. TRIAL REGISTRATION: Clinical Trials.gov NCT00937599.