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We report on clinical, genetic and metabolic investigations in a family with optic neuropathy, non-progressive cardiomyopathy and cognitive disability. Ophthalmic investigations (slit lamp examination, funduscopy, OCT scan of the optic nerve, ERG and VEP) disclosed mild or no decreased visual acuity, but pale optic disc, loss of temporal optic fibers and decreased VEPs. Mitochondrial DNA and exome sequencing revealed a novel homozygous mutation in the nuclear MTO1 gene and the homoplasmic m.593T>G mutation in the mitochondrial MT-TF gene. Muscle biopsy analyses revealed decreased oxygraphic Vmax values for complexes I+III+IV, and severely decreased activities of the respiratory chain complexes (RCC) I, III and IV, while muscle histopathology was normal. Fibroblast analysis revealed decreased complex I and IV activity and assembly, while cybrid analysis revealed a partial complex I deficiency with normal assembly of the RCC. Thus, in patients with a moderate clinical presentation due to MTO1 mutations, the presence of an optic atrophy should be considered. The association with the mitochondrial mutation m.593T>G could act synergistically to worsen the complex I deficiency and modulate the MTO1-related disease.
Assuntos
Cardiomiopatias/genética , Proteínas de Transporte/genética , Homozigoto , Deficiência Intelectual/genética , Mutação , Doenças do Nervo Óptico/genética , RNA de Transferência de Fenilalanina/genética , Adulto , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/patologia , Análise Mutacional de DNA , Complexo I de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Expressão Gênica , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/patologia , Masculino , Potencial da Membrana Mitocondrial/genética , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Disco Óptico/metabolismo , Disco Óptico/patologia , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/patologia , Linhagem , Proteínas de Ligação a RNA , Acuidade VisualRESUMO
The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (râ=â0.562) and its two components muscle mass (râ=â0.516) and non-muscular fat-free mass (râ=â0.452), and also trunk fat mass (râ=â0.383) and waist-to hip ratio (râ=â0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.
Assuntos
Viscosidade Sanguínea , Hemorreologia , Humanos , Viscosidade Sanguínea/fisiologia , Hemorreologia/fisiologia , Agregação Eritrocítica/fisiologia , Hematócrito , ViscosidadeRESUMO
Recent literature shows that exercise is not simply a way to generate a calorie deficit as an add-on to restrictive diets but exerts powerful additional biological effects via its impact on mitochondrial function, the release of chemical messengers induced by muscular activity, and its ability to reverse epigenetic alterations. This review aims to summarize the current literature dealing with the hypothesis that some of these effects of exercise unexplained by an energy deficit are related to the balance of substrates used as fuel by the exercising muscle. This balance of substrates can be measured with reliable techniques, which provide information about metabolic disturbances associated with sedentarity and obesity, as well as adaptations of fuel metabolism in trained individuals. The exercise intensity that elicits maximal oxidation of lipids, termed LIPOXmax, FATOXmax, or FATmax, provides a marker of the mitochondrial ability to oxidize fatty acids and predicts how much fat will be oxidized over 45-60 min of low- to moderate-intensity training performed at the corresponding intensity. LIPOXmax is a reproducible parameter that can be modified by many physiological and lifestyle influences (exercise, diet, gender, age, hormones such as catecholamines, and the growth hormone-Insulin-like growth factor I axis). Individuals told to select an exercise intensity to maintain for 45 min or more spontaneously select a level close to this intensity. There is increasing evidence that training targeted at this level is efficient for reducing fat mass, sparing muscle mass, increasing the ability to oxidize lipids during exercise, lowering blood pressure and low-grade inflammation, improving insulin secretion and insulin sensitivity, reducing blood glucose and HbA1c in type 2 diabetes, and decreasing the circulating cholesterol level. Training protocols based on this concept are easy to implement and accept in very sedentary patients and have shown an unexpected efficacy over the long term. They also represent a useful add-on to bariatric surgery in order to maintain and improve its weight-lowering effect. Additional studies are required to confirm and more precisely analyze the determinants of LIPOXmax and the long-term effects of training at this level on body composition, metabolism, and health.
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Diabetes Mellitus Tipo 2 , Tecido Adiposo/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Exercício Físico/fisiologia , Humanos , Lipídeos , Oxirredução , Consumo de OxigênioRESUMO
The screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), ß-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select "at-risk" patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: (1) the validity of the V'O2-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and (2) the discriminative value of the V'O2-adjusted energy and redox markers, as well as five other V'O2-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V'O2-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V'O2-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V'O2-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of "at-risk" patients is discussed.
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Teste de Esforço , Doenças Musculares , Biomarcadores , Exercício Físico/fisiologia , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Humanos , Músculos , Oxirredução , Consumo de Oxigênio/fisiologiaRESUMO
Many factors in the surrounding environment have been reported to influence erythrocyte deformability. It is likely that some influences represent reversible changes in erythrocyte rigidity that may be involved in physiological regulation, while others represent the early stages of eryptosis, i.e., the red cell self-programmed death. For example, erythrocyte rigidification during exercise is probably a reversible physiological mechanism, while the alterations of red blood cells (RBCs) observed in pathological conditions (inflammation, type 2 diabetes, and sickle-cell disease) are more likely to lead to eryptosis. The splenic clearance of rigid erythrocytes is the major regulator of RBC deformability. The physicochemical characteristics of the surrounding environment (thermal injury, pH, osmolality, oxidative stress, and plasma protein profile) also play a major role. However, there are many other factors that influence RBC deformability and eryptosis. In this comprehensive review, we discuss the various elements and circulating molecules that might influence RBCs and modify their deformability: purinergic signaling, gasotransmitters such as nitric oxide (NO), divalent cations (magnesium, zinc, and Fe2+), lactate, ketone bodies, blood lipids, and several circulating hormones. Meal composition (caloric and carbohydrate intake) also modifies RBC deformability. Therefore, RBC deformability appears to be under the influence of many factors. This suggests that several homeostatic regulatory loops adapt the red cell rigidity to the physiological conditions in order to cope with the need for oxygen or fuel delivery to tissues. Furthermore, many conditions appear to irreversibly damage red cells, resulting in their destruction and removal from the blood. These two categories of modifications to erythrocyte deformability should thus be differentiated.
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Physiological modifications of blood rheology during pregnancy and their alterations in pregnant hypertensive women have been extensively studied in the 1980's. Since vascular resistance is higher in hypertensive pregnant women whose newborns are small-for gestational-age (SGA), we investigated in a personal database if growth retardation of newborns is related to the oxygen delivery index (ratio hematocrit/blood viscosity) and to the difference between hematocrit (Hct) and the prediction of its optimal valued based on Quemada's equation. A sample of 38 hypertensive pregnant women (age 29âyr±1) was compared with 64 controls matched for age and gestational age, studied at 35±1 weeks gestation, extracted from a larger series of 162 pregnant women. On the whole the hypertensive group gave birth to smaller children (pâ=â0.014). Plasma viscosity correlated with blood pressure (BP) only in hypertensive women (râ=â0.403 pâ<â0.05). The bell-shaped curve of predicted optimal Hct of non hypertensive pregnant women was similar to that of non-pregnant women, but in hypertensive women it was shifted toward higher values (pâ=â0.07), and the predicted optimal Hct (but not the actual one) was correlated with systolic blood pressure (SBP) (râ=â0.349 pâ<â0.001) and diastolic blood pressure (DBP) (râ=â0.218 pâ<â0.05). The predicted optimal Hct/viscosity (h/η) ratio was higher in hypertensive women whose newborns exhibited a low birth weight (pâ=â0.03), resulting in a higher discrepancy between actual and model-predicted «ideal¼ values of h/η ratio (pâ=â0.03) and Hct (pâ=â0.02) compared with the subgroup with no growth retardation. Therefore, in hypertensive women whose newborns exhibited a low birth weight, hemorheological parameters predicting oxygen supply are shifted to lower values than predicted by the model.
Assuntos
Pressão Sanguínea/fisiologia , Viscosidade Sanguínea/fisiologia , Retardo do Crescimento Fetal/fisiopatologia , Hematócrito/métodos , Hemorreologia/fisiologia , Hipertensão/fisiopatologia , Oxigênio/fisiologia , Adulto , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
We previously reported that whole body bioelectrical impedance analysis (BIA) measurements are correlated to some hemorheologic factors, suggesting a relationship between viscosity factors and electric properties of flowing blood not only in vitro but also in vivo. Recently we reported that with segmental BIA (analyzing the body considered as composed of 5 cylinders) predictive equations for various determinants of blood viscosity were closer than for the wole body. Another widely used BIA technique uses leg-to-leg impedance measurements so that two cylinders (the two legs) are analyzed. We investigated whether impedance measured with this technique (Tanita TBF-300) is also a predictor of blood viscosity factors. From viscometric measurements performed on venous blood drawn in recreative athletes over the range of shear rates 1 to 6000âs-1 (RHEOMETRE Anton Paar CP 50-1), we found a correlation between leg-leg resistance at 50âkHz (Rx[50âkHz]) and blood viscosity at 1000âs-1 (η1000=â0.0051 Rx[50âkHz]â+â1.3265; râ=â0.521 pâ=â0.028 yielding a prediction of η1000 (Bland Altman plot: bias 0.05 [RANGE - 0.24; 0.34]. Neither plasma viscosity nor the red cell rheology index «k¼ of Quemada's model are correlated with Rx[50âkHz], but hematocrit (Hct) does (Hct (%)â=â0.0217 Rx[50âkHz]â+â33.783; râ=â0.480 pâ=â0.044) yielding a prediction of Hct (Bland Altman plot: bias - 0.11, [range - 1.67; 1.45]. The discrepancy between actual and predicted Hct is also correlated with resistance at 50âkHz (râ=â0.575 pâ=â0.031) as does the discrepancy between actual and predicted Hct/viscosity ratio (râ=â-0.651 pâ=â0.006). Therefore, as other previously studied methods, leg to leg BIA predicts viscosity, suggesting that blood rheology may influence the passage of an electric current in the legs.
Assuntos
Viscosidade Sanguínea/fisiologia , Impedância Elétrica/uso terapêutico , Hematócrito/métodos , Hemorreologia/fisiologia , Perna (Membro)/irrigação sanguínea , Adulto , Feminino , Humanos , Masculino , ViscosidadeRESUMO
Hematocrit increases during exercise and is usually decreased after regular training. However the interpretation of these facts is ambiguous since hematocrit is both a determinant of oxygen supply and the major determinant of blood viscosity. Classically hematocrit was assumed to impair blood flow, but it has been evidenced to exert a biphasic effect on it. In order to cope with these two apparently opposite effects of hematocrit, hemorheologists have proposed the concept hematocrit/viscosity ratio (h/η). This h/η ratio is related to tissue oxygenation in vascular diseases (eg, POAD) but not in healthy subjects. h/η displays a bell-shaped curve as a function of hematocrit and the hematocrit value corresponding to the maximal h/η can be assumed to be a theoretically optimal hematocrit. We propose to analyse exercise-related alterations in hematocrit according to this theoretical approach, viscosity at high shear rate being reconstructed with Quemada's equation from actual plasma viscosity and red cell rigidity at various hematocrit levels. While theoretical and actual h/η are fairly correlated in athletes both before and after exercise, actual hematocrit is lower at rest and higher after exercise compared to the theoretical one. The main statistic correlate of these discrepancies between actual and predicted hematocrit is red cell rigidity. Submaximal exercise acutely decreases the h/η ratio (despite increasing both hematocrit and viscosity). This change is well predicted by the model and there is a strong correlation between predicted and actual h/η ratio. Endurance training tends to increase h/η and to reduce the discrepancy between predicted and actual hematocrit. Accordingly trained athletes have a higher h/η (both model-predicted and actual) than sedentary subjects, and a lower hematocrit, this lowering being rather correlated to training volume than to fitness improvement. On the whole, this approach suggests that homeostatic "viscoregulation" in athletes results in a fine tuning of h/η which seems to be a closely regulated parameter. Hematocrit alterations in this context are an adaptation involved in this regulation.
Assuntos
Viscosidade Sanguínea/fisiologia , Exercício Físico/fisiologia , Hematócrito/métodos , Adulto , Feminino , Hemorreologia/fisiologia , Humanos , MasculinoRESUMO
Rheological properties of plasma and blood cells are markedly influenced by the surrounding milieu: physicochemical factors, metabolism and hormones. Acid/base status, osmolality, lipid status, plasma protein pattern, oxidative stress induced by increased free radicals production, endothelium-derived factors such as nitric oxide (NO), achidonic acid derivatives modulate both red blood cell (RBC) and white cell mechanics. Therefore, regulatory axes involving liver, endothelium, kidney, pancreas, adrenal gland, endocrine heart, adipose tissue, pituitary gland, and surely other tissues play important roles in the regulation of blood fluidity. A comprehensive picture of all this complex network of regulatory loops is still unavailable but current progress of knowledge suggest that some attempts can currently be made.
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Homeostase , Reologia/métodos , HumanosRESUMO
We investigated whether the concept of hematocrit/viscosity (h/η) ratio explains the "paradox of hematocrit in athletes", by calculating a "theoretical optimal hematocrit" (i.e., associated with the higher h/η value predicted with Quemada's equation from plasma viscosity, and erythrocyte rigidity index) before and after exercise. 14 rugby players (19-31 yr; weight 65.8-109.2âkg; height 1.7-1.96âm; BMI 21.7-33.1âkg/m2) underwent a standardized submaximal exercise session on cycloergometer corresponding to 225 kjoules over 30âmin. The rheologic response to exercise was measured with the MT90 viscometer and the Myrenne aggregometer. After exercise there was an increase in whole blood viscosity (pâ<â0.05) and hematocrit (pâ<â0.005) and a decrease in h/η ratio (from 14.7±0.34 to 12.9±0.37, pâ<â0.005). There was an increase in viscometric RBC rigidity indexes "Tk" and "k" in 9/14 subjects. Predicted and actual h/η are fairly well correlated (preexercise râ=â0.998, pâ<â0.001; postexercise râ=â0.985 pâ<â0.001) but actual h/η was lower than predicted (preexercise pâ=â0.005; postexercise pâ=â0.02). This discrepancy between predicted and measured hematocrit was not correlated to dehydration or plasma viscosity but was correlated to red cell rigidity (râ=â0.774, pâ<â0.01) and its exercise-induced change (râ=â0.858, pâ<â0.01). This study suggests that h/η, although it is not directly correlated to parameters of exercise performance, is precisely regulated during exercise according to the classic concept of "viscoregulation", and that the prediction of the theoretical optimal values of h/η and hematocrit by models may help to interpret the actual values of these parameters. However, these models need to be more extendedly tested and improved.
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Deformação Eritrocítica/fisiologia , Futebol Americano/fisiologia , Hematócrito/métodos , Adulto , Atletas , Viscosidade Sanguínea , Exercício Físico/fisiologia , Hemorreologia/fisiologia , Humanos , Masculino , Adulto JovemRESUMO
The hemorheological theory of optimal hematocrit suggests that the best value of hematocrit (hct) should be that which results in the highest value of the hematocrit/viscosity (h/η) ratio. Trained athletes compared to sedentary subjects have a lower hct, but a higher h/η, and endurance training reduces the discrepancy between the actual hct and the ⪡ideal⪢ hct that can be predicted with a theoretical curve of h/η vs hct constructed with Quemada's model. In this study we investigated what becomes this homeostasis of h/η and hct during acute exercise in 19 athletes performing a 25âmin exercise test. VO2max is negatively correlated to resting hct and positively correlated to discrepancy between actual and ideal resting hct which is correlated to the maximal rise in hct during exercise. Predicted and actual values of the h/η were fairly correlated (râ=â0.970 pâ<â0.001) but the actual value was lower at rest and this discrepancy vanished at 25âmin exercise. Exercise-induced decrease in discrepancy between actual and theoretical h/η was negatively correlated with the score of overtraining. All these findings suggest that h/η is a regulated parameter and that its model-predicted ⪡optimal⪢ values yield a ⪡theoretical optimal⪢ hct which is close to the actual value and even closer when athletes are well trained. In addition, acute exercise sets h/η closer from its predicted ideal value and this adaptation is impaired when athletes quote elevated scores on the overtraining questionnaire.
Assuntos
Exercício Físico/fisiologia , Hematócrito/métodos , Hemorreologia , Adolescente , Adulto , Atletas , Viscosidade Sanguínea , Humanos , Masculino , Adulto JovemRESUMO
Equations of blood viscosity provide a prediction of the 'optimal' hematocrit' (hct) as the hct resulting in the highest value of the bell-shaped curve of hematocrit/viscosity ratio h/η. We investigated if overweight and obesity have an influence on these parameters. We compared 32 normal weight subjects, 40 overweight (BMI 25-30) and 38 obese subjects. There was no difference in the theoretical curve of h/η. The actual h/η is the same in the 3 groups but is always higher than the theoretical h/η in all groups. The actual h/η is lower in overweight than controls (pâ=â0.011). Modeling yields the same value of theoretical optimal hct across BMI classes. The 3 groups have the same values of actual hct, but actual is significantly lower than optimal in all cases (pâ<â0.001). Hematocrit is lower than predicted due to a discrepancy between predicted and actual h/η which is due to the inter-subject variability of RBC rigidityâ... â The discrepancy between optimal and actual h/η is negatively correlated to RBC rigidity indexes even if the model uses a fixed value of these indexes. Thus keeping in mind that the optimal hct should not be the same in the various parts of the vascular bed, its theoretical prediction with Quemada's equation appears to predict a value higher than actual hematocrit but well correlated to it, and the agreement between optimal and actual hct is dependent on RBC flexibility. This leads to think that the body sets hematocrit below its ideal value in sedentary subjects in order to cope with the need of increasing blood viscosity factors in case of exercise without impairing O2 supply to tissues.
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Hematócrito/métodos , Hemorreologia , Obesidade/sangue , Sobrepeso/sangue , Adulto , Viscosidade Sanguínea , Feminino , Humanos , MasculinoRESUMO
We investigated to what extent a prediction of the 'ideal' hematocrit based on individual hemorheological profile with an equation of viscosity is relevant in trained athletes, and how the agreement between theoretical and actual values is modified by changes in training volume and performance. Elite soccer players (national level: 18-32 yr, weight 61-83âkg, body mass index 20.9-25.8âkg/m2) were seen twice at one year interval. Hemorheologic parameters were measured with the MT90 viscometer and the Myrenne aggregometer the theoretical bell-shaped curve of hematocrit/viscosity ratio as a function of hematocrit was reconstructed with Quemada's equation using actual plasma viscosity and red cell rigidity to predict hematocrit/viscosity at various hematocrit levels. RBC aggregation is correlated at baseline with fat mass (M1â=â0.552 pâ<â0.02) and changes in aggregation are related to changes in fat mass (Mâ=â0.652, pâ<â0.05; M1â=â0.647, pâ<â0.05). Predicted and actual hematocrit are correlated (râ=â0.644, pâ<â0.05) but exhibit discrepancies (mean difference -1% range [3.24 to 1.24]) and those discrepancies are inversely correlated to the level of predicted hematocrit (râ=â-0.912, pâ<â0.01), to systolic blood pressure (râ=â-0.626, pâ<â0.05), and to the overtraining score (râ=â-0.693, pâ<â0.05). After one year changes in hematocrit are a close reflect of the change in training volume (râ=â-0.877, pâ<â0.01) but are not correlated to fitness changes. Therefore in these athletes i) systemic hematocrit is close to its predicted 'ideal value", suggesting the accuracy of the prediction; ii) red cell aggregation is correlated to fat mass even in nonobese subjects; iii) hematocrit is lower than predicted by the model when markers of sympathetic tone (systolic blood pressure, overtraining score) are increased; iv) weekly training volume appears the main determinant of the reduction of hematocrit.
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Hematócrito/métodos , Hemorreologia , Futebol/fisiologia , Adolescente , Adulto , Atletas , Viscosidade Sanguínea , Agregação Eritrocítica , Feminino , Seguimentos , Humanos , MasculinoRESUMO
We previously reported that low intensity endurance training in sedentary patients suffering from the metabolic syndrome improves blood rheology, mostly due to a decrease in plasma viscosity correlated with an increase in cardiorespiratory fitness. We investigated whether these findings can be extended to type-2 diabetics. 22 diabetics (11 women and 10 men, age: 52.00 ± 2.9 yr, BMI: 32.47 ± 1.17âkg/m(2)) were tested before and after 2 months. Eight of them were trained (2 to 3×45âmin/wk) at the power intensity where lipid oxidation reaches a maximum (LIPOX max) and thirteen served as controls. Over this period the only significant hemorheological effect of training was a decrease in RBC aggregation "M" (-1.25 ± 0.357 pâ=â0.01) in the trained group. Subjects who lost weight exhibited a decrease in plasma viscosity (from 1.46 ± 0.013 to 1.38 ± 0.02 pâ< â0.01). Changes in waist circumference are associated with changes in hematocrit (râ=-0.952 pâ=â0.01); plasma viscosity (râ=-0.91; pâ=â0.03); RBC aggregation ("M" râ=â0.940; pâ=â0.02). Subjects can also be divided into those who improved their aerobic capacity VO(2max) and those whose VO(2max) decreased or remained unchanged. An increase in VO(2max) is associated with a decrease in whole blood viscosity (râ=-0.79 pâ=â0.06) explained by an improvement in RBC rigidity "Tk" (râ=-0.963 pâ=â0.002). This study suggests that in Type 2 diabetic patients: (a) viscosity factors might be less responsive to training than in non diabetic individuals; (b) visceral fat loss is the main determinant of changes in hematocrit, plasma viscosity and RBC aggregation;
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Viscosidade Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/sangue , Exercício Físico/fisiologia , Hemorreologia , Agregação Eritrocítica , Deformação Eritrocítica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
In line with recent literature showing that both general adiposity and abdominal adiposity are independently associated with the risk of death, we recently reported that body mass index (BMI) and waist-to hip ratio (WHR) were independent predictors of blood viscosity, related to different determinants of viscosity (for BMI: plasma viscosity and red cell aggregation; for WHR: hematocrit). Since this report was challenged by a study showing that abdominal adiposity (as measured with waist circumference WC and not WHR) is the only independent determinant of viscosity, we re-assessed on our previous database correlations among viscosity factors, BMI, WHR and WC. Blood viscosity was correlated to BMI (râ=â0.155 pâ=â0.004), WHR (râ=â0.364; pâ=â0.027) and WC (râ=â0.094; pâ=â0.05). Hematocrit was correlated to WHR (râ=â0.524) but neither to BMI (râ=-0.021) nor waist circumference (râ=â0.053). WC was correlated with plasma viscosity (râ=â0.154; pâ=â0.002) while WHR was not (râ=-0.0102 NS). A stepwise regression analysis selected two determinants of whole blood viscosity at high shear rate: BMI (pâ=â0.0167) and WC (pâ=â0.0003) excluding WHR. Therefore, in this sample, abdominal fatness expressed by WC and whole body adiposity remain independent determinants of blood viscosity. WHR and WC have not the same meaning, WC measuring the size of abdominal fat while WHR measuring the shape of body distribution regardless the degree of fat excess. Interestingly, hematocrit is rather related to shape (even within a normal range of body size) than the extent of abdominal fatness, and is not related to whole body adiposity.
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Adiposidade/imunologia , Viscosidade Sanguínea/imunologia , Hemorreologia , Obesidade Abdominal/sangue , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Agregação Eritrocítica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relação Cintura-Quadril , Adulto JovemRESUMO
We examined whether "metabolically healthy obesity" (MHO) is associated or not with hemorheologic alterations. We studied 110 subjects: 32 normal weight; 40 overweight; 38 obese. Overweight and obese subjects were divided into two subgroups according to the occurrence or not of a metabolic syndrome (METS). Subjects were thus categorized as follows: (1) metabolically healthy and normal weight (MHNW); (2) metabolically healthy but overweight (MHOW); (3) metabolically abnormally overweight (MAOW); (4) metabolically healthy but obese (MHOB); and (5) metabolically abnormally obese (MAOB). Across those various subgroups whole blood viscosity and plasma viscosity were not statistically different, although there was a tendency to higher values in the subgroups with METS compared to those without METS. RBC aggregation "M" was higher in all obese than MHNW (7.25 ± 0.64 vs 4.31 ± 0.44 pâ< â0.001 and was also higher in MHOB than MHNW (8.22 ± 1.07 vs 4.31 ± 0.44 vs 8.22 ± 1.07 pâ< â0.02). It was higher in all obese subjects than in all overweight subjects (7.25 ± 0.64 vs 5.22 ± 0.40 pâ< â0.01) but the difference between overweight and MHNW was not significant. M was negatively correlated with insulin sensitivity (râ=-0.457 pâ=â0.0008). On the whole increased RBC aggregability "M" seems to be more related to fatness by its own than to the occurrence of metabolic abnormalities. MHO is not associated with alterations of blood viscosity at high shear rate, but exhibits a slight increase in RBC aggregability. These data are consistent with the assumption that MHO is on the whole a "hemorheologically healthy" situation, but that RBC aggregability is proportional to fatness even in "healthy" conditions, as already observed in samples of normal weight athletes.
Assuntos
Hemorreologia , Obesidade/metabolismo , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Impedância Elétrica , Agregação Eritrocítica , Feminino , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Adulto JovemRESUMO
In a precedent study we observed that overall adiposity evaluated with the body mass index (BMI) was correlated with plasma viscosity and red blood cells (RBC) aggregation while abdominal obesity as assessed with the waist to hip ratio (WHR) was correlated with hematocrit. We investigated this issue in 129 women (age 15-65 years, BMI: 15 to 44 kg/m(2), WHR: 0.65 to 1.13, fatness: 12-58%) who were divided into fatness groups: 17 underweight women (BMI <18.5), 75 normal weigh (BMI 18.5-24.9), 11 overweight (BMI 25-29.9), and 26 obese (BMI >30) divided according to WHR into 13 lower body and 13 upper body obese women. Whole blood viscosity significantly increases across obesity classes, and is higher in upper body than in lower body obesity (2.84 ± 0.08 vs 3.29 ± 0.09 mPa.s, p < 0.05). The correlations between whole blood viscosity and BMI (r = 0.383 p < 0.01) and WHR (r = 0.364 p < 0.01) are found again. The former is explained by correlations of BMI with plasma viscosity (r = 0.303 p < 0.01) and red cell rigidity (r = 0.356 p < 0.01) and the latter is only explained by a correlation between WHR and hematocrit (r = 0.524 p < 0.01). BMI is also correlated with RBC aggregation parameters. Actually, when total fatness is evaluated with the percentage of fat (%fat) given by bioimpedance analysis (BIA), the picture is slightly different, since %fat is correlated with whole blood viscosity and RBC aggregation parameters but not with hematocrit, plasma viscosity and red cell rigidity. Fat free mass is also correlated with whole blood viscosity (r = 0.227 p < 0.02) due to a correlation with hematocrit (r = 0.483 p < 0.01) but neither RBC rheology nor plasma viscosity. This study shows that fatness by its own is associated with increased red cell aggregation, that abdominal fat increases blood viscosity due to a rise in hematocrit, and that overall body size as assessed with the BMI is associated with increased plasma viscosity and red cell rigidity.
Assuntos
Obesidade/sangue , Adolescente , Adulto , Idoso , Viscosidade Sanguínea/fisiologia , Composição Corporal , Agregação Eritrocítica/fisiologia , Feminino , Hematócrito , Hemorreologia , Humanos , Pessoa de Meia-Idade , Obesidade/metabolismo , Adulto JovemRESUMO
Classic studies on exercise hemorheology evidenced that blood fluidity is impaired during exercise (short term exercise-induced hyperviscosity) and is improved as a result of regular exercise practice (hemorheologic fitness). Extensive description of these events led to the concepts of "the triphasic effects of exercise", "the paradox of hematocrit", and "the hemorheological paradox of lactate". However, some results obtained in training studies do not fit with this classical picture and cannot be explained by a simplistic paradigm based on the Hagen-Poiseuille law. Taking into account the non-linearity of the effects of viscosity factors on blood flow and oxygen delivery helps to elaborate another picture. For example, moderately high values of hematocrit and erythrocyte rigidity induced by high intensity exercise are likely to trigger a physiological vasodilation improving circulatory adaptation (rather than limiting performance as was previously assumed). This may apply to the acute rise in red cell rigidity observed during strenuous exercise, and also to the paradoxical rise in hematocrit or red cell rigidity observed after some training protocols and that did not fit with the previous (simplistic) paradigms. The "healthy primitive lifestyle" hypothesis assumes that evolution has selected genetic polymorphisms leading to insulin resistance as an adaptative strategy to cope with continuous low intensity physical activity and a special alimentation based on lean meat and wild herbs (i.e., moderately high in protein, rich in low glycemic index carbohydrates, and poor in saturated fat). We propose here that this model may help to explain on an evolutionary perspective these apparently inconsistent findings. The pivotal explanation is that the true physiological picture would be that of an individual whose exercise and nutritional habits are close from this lifestyle, both sedentary subjects and trained athletes representing situations on the edge of this model.
Assuntos
Eritrócitos/fisiologia , Exercício Físico/fisiologia , Hemorreologia/fisiologia , Viscosidade Sanguínea/fisiologia , Agregação Eritrocítica/fisiologia , Deformação Eritrocítica/fisiologia , Hematócrito , Humanos , Resistência à Insulina/fisiologia , Síndrome Metabólica/fisiopatologiaRESUMO
We investigated the measurement of insulin sensitivity (S I) with a standardized hyperglucidic breakfast (SHB) compared to minimal model analysis of an intravenous glucose tolerance test (S I-IVGTT) in 17 patients clinically referred as type 2 diabetics, not yet treated by insulin, and representing a wide range of body mass index and S I. To classify the patients, ten meal-tolerance test-based calculations of S I (MTT-S I) were compared to S I-IVGTT, and their reference values and distribution were measured on a separate sample of 200 control SHBs and 209 control IVGTTs. Eight MTT-SI indices exhibit significant correlations with S I-IVGTT: Mari's OGIS index, BIGTT-SI|0-30-120, BIGTT-SI|0-60-120, 1/G b I m, Caumo's oral minimal model (OMM), Sluiter's index "A" = 10(4)/(I p·G p), Matsuda's composite index given by the formula ISIcomp = 10(4)/(I b G b I m G m)(0.5), S I = 1/I b G b I m G m with r (2) ranging between 0,53 and 0,28. S I-IVGTT and S I-MTT exhibited in the lower range a very different (non-normal) pattern of distribution and thus the cutoff value for defining insulin resistance varied among indices. With such cutoffs, S I-MTT < 6.3 min(-1)/(µU/ml) 10(-4) with Caumo's OMM was the best predictor of insulin resistance defined as S I-IVGTT < 2 min(-1)/(µU/ml) 10(-4). Other indices, including OGIS and BIGTT, resulted in more misclassifications of patients. HOMA-IR and QUICKI were poor predictors. The formula [Formula: see text] satisfactorily predicts IVGTT-derived glucose effectiveness in type 2 diabetics. Thus, SHB appears suitable for the measurement of S I and S G in type 2 diabetics, and the OMM seems to provide the most accurate SHB-derived index in this population.
Assuntos
Desjejum , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Tolerância a Glucose/métodos , Resistência à Insulina , Glicemia/análise , Índice de Massa Corporal , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
Body composition and nutrition have been reported to be correlated with blood rheology. However, in sedentary and in physically active individuals these relationships seem to be not exactly similar. This study investigated whether exercise training status influences these relationships. 32 athletes (ATH) (age: 25 ± 0.7 yr; body mass index (BMI): 23.75 ± 0.23 kg/m2) were compared to 21 sedentary subjects (SED) (age: 45.19 ± 2.90; BMI = 33.41 ± 1.33) with nutritional assessment (autoquestionnaire), bioelectrical impedancemetry, viscometry at high shear rate (MT90) and Myrenne aggregometer. Subjects differ according to age, weight and adiposity parameters. Their eating behavior is different: ATH eat a higher percentage of protein (p < 0.005), a lower percentage of lipid (p < 0.05), and a higher total amount of carbohydrate (+31% p < 0.02). Their viscosity factors are similar except plasma viscosity which is higher in SED than ATH (1.51 ± 0.03 vs 1.43 ± 0.02 mPa.s, p < 0.05). In both ATH and SED, abdominal obesity (waist-to-hip ratio or WHR) is associated with impairments in blood rheology, but not exactly the same. In ATH, WHR is associated with an increase in hematocrit (r = 0.647; p = 0.009), plasma viscosity (r = 0.723; p = 0.002), and caloric (and CHO) intake moderately increase RBC rigidity (r = 0.5405; p = 0.0251) and aggregability (r = 0.3366 p = 0.0596). In SED the picture is different, adiposity increases hematocrit (r = 0.460; p = 0.048), abdominal fatness increases blood viscosity independent of hematocrit, and CHO intake is associated with lower RBC aggregability (r = -0.493; p = 0.0319).