Priscila A. Maranhão

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

BackgroundObesity 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.MethodsObese 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).ResultsT0 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).ConclusionBrazil 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 RegistrationClinical Trials.govNCT00937599

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.

Microvascular dysfunction: a direct link among BMI, waist circumference and glucose homeostasis in young overweight/obese normoglycemic women?

Objective:Capillary recruitment is impaired in obesity (OB), possibly worsening glucose and insulin availability to target organs. In this study, we investigated whether functional microvascular parameters were correlated with clinical–anthropometrical data and whether these parameters would influence OB-related metabolic disorders, especially glucose homeostasis, in young overweight (OW)/obese women.Design:Cross-sectional clinical study of microvascular reactivity in young OW/obese women.Subjects and methods:A total of 10 lean (23.1±3.2 years, body mass index (BMI) 22.3±1.6 kg m−2) and 42 OW/obese (24.9±3.5 years; BMI 34.5±5.7 (25.7–46.5) kg m−2) sedentary non-smoking women were evaluated. Lipid profile, fasting plasma glucose (PG), post-load PG (75 g–2 h), insulin, C-reactive protein, HOMA-IR (homeostasis model assessment for insulin resistance) index and anthropometric variables (weight, BMI, waist and hip circumferences, waist-to-hip ratio and blood pressure (BP)) were determined. Functional microvascular parameters (functional capillary density, red blood cell velocity at baseline and peak (RBCVmax), and time taken to reach RBCVmax (TRBCVmax) during post-occlusive reactive hyperemia after 1 min arterial occlusion) were evaluated by nailfold videocapillaroscopy.Results:The time taken to reach RBCVmax was significantly longer in OW/obese patients compared with control subjects (8.6±2.4 versus 5.7±1.1 s, P<0.001), and its delay was directly associated with adiposity levels, systolic BP and insulin resistance, and inversely related to high-density lipoprotein-cholesterol. Post-load PG could be correlated with TRBCVmax (R=0.48, P<0.05) and RBCVmax (R=−0.29, P<0.05), and it was influenced by weight, waist circumference and TRBCVmax (adjusted R 2=24%) as well.Conclusions:In the investigated group of young OW/obese women, the direct correlation between post-load PG and TRBCVmax links microvascular parameters with metabolic variables and suggests a key role for microcirculation in OB-related metabolic disorders.

Novel findings in the cephalic phase of digestion: A role for microcirculation?☆

The cephalic phase of digestion (CPD) has been extensively investigated in terms of digestion and metabolism. Nevertheless, microcirculatory changes required to prepare peripheral tissues in order to dispose nutrients have never been assessed. In this study, microvascular function has been evaluated to determine its behavior and potential association to hormonal secretions during CPD. Thirty-nine healthy male subjects, 23.4 ± 0.5 years (mean ± SD) and BMI of 23.3 ± 2.3 kg/m(2), were randomized into receiving cognitive-sensorial stimuli to elicit CPD (CPD group, n=20) or not (control group, n=19), after a 12-h overnight fast. Main outcomes were differences in resting and peak functional capillary density (FCD, cap/mm(2)); resting red blood cell velocity (RBCV), peak RBCV (RBCV(max)) and time taken to reach it (TRBCV(max)); peak flow and vasomotion, before and after CPD and their associations with insulin and/or pancreatic polypeptide (PP). In the CPD group, basal FCD (24.9 ± 7.6 to 28.3 ± 8.1, p=0.005), peak FCD (27.8 ± 6.3 to 32.6 ± 7.1, p=0.002), RBCV (0.306 ± 0.031 to 0.330 ± 0.027 mm/s, p=0.005), RBCV(max) (0.336 ± 0.029 to 0.398 ± 0.292 mm/s, p=0.005) and peak flow (23.5 ± 14.3 to 26.9 ± 15.8 PU, p<0.01) increased while TRBCV(max) decreased (4.9 ± 1.5 to 3.5 ± 1.2s, p=0.01). No significant changes could be detected in the control group. Groups have not presented differences for insulin, but PP significantly increased in the CPD group and was positively associated to basal FCD increase (rho=0.527, p=0.03). In conclusion, neurally-mediated anticipatory responses of digestion elicited functional capillary recruitment associated to PP in healthy men, suggesting a precocious role for microcirculation in the physiology of digestion and nutrient homeostasis.

Microcirculatory function in postmenopausal women: Role of aging, hormonal exposure and metabolic syndrome

Menopausal hormone therapy (HT) has shown conflicting cardiovascular endpoints, depending on the women studied. The endothelium is the main site for sex steroids cardiovascular action. To assess the influence of age, previous hormonal exposure and of metabolic syndrome (MS) on microcirculatory function, we studied 68 normotensive non-diabetic postmenopausal women, 34-70 years old, by dynamic nailfold videocapillaroscopy evaluating red blood cell velocity (RBCV) at baseline and during the reactive hyperemia response after 1 min ischemia (RBCV(max)) and time taken to reach it (TRBCV(max)). There was an inverse correlation between RBCV and RBCV(max), versus age (p=0.02 for both) and time since menopause (TSM, p=0.01 and p=0.03, respectively). Women who used oral contraceptives in the past showed higher RBCV (1.51+/-0.10 vs. 1.43+/-0.09 mm/s, p=0.01) and RBCV(max) (1.70+/-0.11 vs. 1.63+/-0.07 mm/s, p=0.03) compared to never user ones. A longer time after menopause without HT was associated to lower RBCV(max) (p=0.05). Women with MS had longer TRBCV(max) (9.85+/-1.77 vs. 8.47+/-1.71 s, p=0.02), as well as those with higher hematocrit, hemoglobin and leukocyte counts (p=0.03, p=0.01 and p=0.03, respectively) and lower HDL (p=0.03). In conclusion, in postmenopausal women of low cardiovascular risk, advanced age, longer TSM, longer time after menopause without HT and MS were associated to microcirculatory function impairment, whereas past use of oral contraceptives seemed to have a protective effect.

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

BackgroundWe aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements.MethodsData 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 (RBCVmax), and the time taken to reach RBCVmax (TRBCVmax).ResultsA 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 TRBCVmax varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCVmax, but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCVmax). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity.ConclusionsIn 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.

Early postmenopausal women with cardiovascular risk factors improve microvascular dysfunction after acute estradiol administration.

ObjectiveThis study aimed to compare endothelial microcirculatory function in hypertensive and diabetic (HD) and healthy postmenopausal women before and after nasal application of 17&bgr;-estradiol. MethodsSeventy-one women aged 42 to 59 years within 10 years of menopause, divided into HD (n = 31) and similar-age healthy (n = 40) women were evaluated noninvasively through nailfold videocapillaroscopy before and 1 hour after estradiol, measuring basal (RBCV) and maximum (RBCVmax) red blood cell velocity after 1 minute of arterial occlusion, representing baseline and endothelial-mediated vasodilation, and time to reach RBCVmax (TRBCVmax), representing microvascular compliance/stiffness. ResultsHot flashes did not differ from or affect microvascular results. Before estradiol, HD showed lower RBCV (1.495 ± 0.20 vs 1.52 ± 0.10 mm/s, P = 0.019), borderline lower RBCVmax (1.655 ± 0.09 vs 1.706 ± 0.10 mm/s, P = 0.054), and shorter TRBCVmax (7.94 ± 1.44 vs 8.8 ± 2.03 s, P = 0.011) compared with healthy women. After estradiol, RBCV and RBCVmax increased, and TRBCVmax decreased in both groups (P = 0.0001 for all). HD women showed a higher RBCV increment (14.6% ± 2% vs 11.1 ± 1.4%, P = 0.021) associated with a smaller TRBCVmax reduction (23.6% ± 2% vs 31% ± 2%, P = 0.045). Changes in RBCVmax did not differ between HD (11.6% ± 1%) and healthy (8.3% ± 1.3%, P = 0.1) women. RBCV, RBCVmax, and TRBCVmax absolute values after estradiol were similar between groups. Past oral contraceptive exposure (P = 0.035) and cigarette smoking (P = 0.047) influenced healthy women’s microvascular responses to estradiol, whereas triglyceride levels impaired HD vasodilation (P = 0.028). ConclusionsBefore estradiol, HD presented impaired microvascular dilation and compliance compared with control women of similar age. After estradiol, HD recovered microvascular endothelial-mediated dilation, reaching similar absolute values, but the smaller reduction in TRBCVmax suggests irreversible microvascular stiffness.

Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.

Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.

Endothelial-mediated microcirculatory responses to an acute estradiol test are influenced by time since menopause, cumulative hormone exposure, and vasomotor symptoms.

Objective:The aim of this study was to determine which factors could influence microcirculatory responses to an acute estradiol test during postmenopause. Methods:Dynamic nailfold videocapillaroscopy was performed in 68 healthy 34- to 70-year-old postmenopausal women before and 1 hour after administration of 300 &mgr;g nasal estradiol. Red blood cell velocity (RBCV; mm/s) at rest and after the release of 60-second arterial occlusion (RBCVmax; mm/s) and time to reach it (TRBCVmax; s) were correlated to clinical and laboratory data. Results:After estradiol administration, RBCV and RBCVmax increased by 13.4% and 9.4%, respectively, and TRBCVmax decreased by 29.1% (P = 0.0001 for all). These changes were not associated to the womens age but rather to time since menopause (P = 0.04; r = 0.245) and previous duration of hormone therapy (P = 0.03; r = 0.324). Past users of oral contraceptives presented higher velocities but smaller increases compared with never users (12.4% vs 17.7%, P = 0.022, for RBCV and 8.4% vs 13.7%, P = 0.028, for RBCVmax), and triglyceride levels were negatively associated to velocity increases (P = 0.05 and r = −0.243 for RBCV and P = 0.03 and r = −0.261 for RBCVmax) after estradiol administration. Previous smokers showed a smaller reduction in TRBCVmax, associated directly to total estimated number of smoked cigarettes (P = 0.03; r = −0.468). The reduction in TRBCVmax was also inversely related to the intensity of current vasomotor symptoms (P = 0.04; r = −0.252). Conclusions:Changes in RBCVs and TRBCVmax after estradiol administration indicate an increase in endothelial-dependent vasodilatation and vascular elasticity, respectively. Moreover, maintenance of endothelial responsiveness depends on cumulative exposure to sex steroids, duration of hormone deprivation, and triglyceride levels. Past smoking and current vasomotor symptoms could be associated to microvascular wall stiffness/elasticity.

Dynamic nailfold videocapillaroscopy may be used for early detection of microvascular dysfunction in obesity

OBJECTIVES It has been hypothesized that obesity is the primary cause of microvascular dysfunction (MD), which could be a pathway to increase blood pressure and decrease insulin sensitivity. Due to the high prevalence of this metabolic disorder in the world today, the aim of this study was to investigate which is the most appropriate videocapillaroscopic method, between nailfold and dorsal finger, to assess microvascular function in obese patients since both techniques are non-invasive and could be used for early detection as well as for follow-up. METHODS Eighteen lean [27.8±6.2years, body mass index (BMI) 21.8±1.8kg/m(2)] and nineteen obese (30.8±4.6years; BMI 32.3±1.5kg/m(2)) women participated in the study. Dynamic nailfold videocapillaroscopy assessed morphological (capillary diameters) and functional [functional capillary density (FCD); red blood cell velocity (RBCV) at baseline and peak and time (TRBCVmax) taken to reach it during the post-occlusive reactive hyperemia (PORH) response, after 1-min ischemia] parameters; while dorsal finger videocapillaroscopy assessed FCD at rest and capillary recruitment during PORH and post-venous occlusion. RESULTS RBCV (0.32±0.01 vs. 0.30±0.01mm/s; p<0.0001) and RBCVmax (0.32±0.01 vs. 0.30±0.015mm/s; p=0.0020) were significantly higher in control subjects compared to the obese group. Moreover, TRBCVmax was prolonged in the obese group compared to control one (3.5±1.4 vs. 5.5±1.3s; p=0.0001). Multiple regression analysis showed that these variables were influenced by some others, especially those related to adiposity and metabolic disease. On the other hand, dorsal finger videocapillaroscopy did not show any significant differences between groups. CONCLUSION Our results strongly suggest that microvascular dysfunction consequent to obesity could be better detected by dynamic nailfold videocapillaroscopy than by dorsal finger videocapillaroscopy.