Exercise-induced changes in hematocrit and hematocrit/viscosity ratio in male rugby players.

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 65.8-109.2 kg; height 1.7-1.96 m; BMI 21.7-33.1 kg/m2) underwent a standardized submaximal exercise session on cycloergometer corresponding to 225 kjoules over 30 min. 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 (p < 0.05) and hematocrit (p < 0.005) and a decrease in h/η ratio (from 14.7±0.34 to 12.9±0.37, p < 0.005). 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 r = 0.998, p < 0.001; postexercise r = 0.985 p < 0.001) but actual h/η was lower than predicted (preexercise p = 0.005; postexercise p = 0.02). This discrepancy between predicted and measured hematocrit was not correlated to dehydration or plasma viscosity but was correlated to red cell rigidity (r = 0.774, p < 0.01) and its exercise-induced change (r = 0.858, p < 0.01). 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.

« Optimal ¼ vs actual hematocrit in obesity and overweight.

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 (p = 0.011). 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 (p < 0.001). 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 rigidity ...   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.

One-year follow-up of blood viscosity factors and hematocrit/viscosity ratio in elite soccer players.

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 61-83 kg, body mass index 20.9-25.8 kg/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 (M1 = 0.552 p < 0.02) and changes in aggregation are related to changes in fat mass (M = 0.652, p < 0.05; M1 = 0.647, p < 0.05). Predicted and actual hematocrit are correlated (r = 0.644, p < 0.05) but exhibit discrepancies (mean difference -1% range [3.24 to 1.24]) and those discrepancies are inversely correlated to the level of predicted hematocrit (r = -0.912, p < 0.01), to systolic blood pressure (r = -0.626, p < 0.05), and to the overtraining score (r = -0.693, p < 0.05). After one year changes in hematocrit are a close reflect of the change in training volume (r = -0.877, p < 0.01) 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.

Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women.

CONTEXT: Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity. OBJECTIVES: We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development. METHODS: 30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression. RESULTS: Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR. CONCLUSION: Our results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.

Hemorheologic effects of low intensity endurance training in type 2 diabetic patients: A pilot study.

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 ± 1.17 kg/m(2)) were tested before and after 2 months. Eight of them were trained (2 to 3×45 min/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 p = 0.01) in the trained group. Subjects who lost weight exhibited a decrease in plasma viscosity (from 1.46 ± 0.013 to 1.38 ± 0.02 p <  0.01). Changes in waist circumference are associated with changes in hematocrit (r =-0.952 p = 0.01); plasma viscosity (r =-0.91; p = 0.03); RBC aggregation ("M" r = 0.940; p = 0.02). 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 (r =-0.79 p = 0.06) explained by an improvement in RBC rigidity "Tk" (r =-0.963 p = 0.002). 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;

Are metabolically healthy obese patients also hemorheologically healthy?

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 p <  0.001 and was also higher in MHOB than MHNW (8.22 ± 1.07 vs 4.31 ± 0.44 vs 8.22 ± 1.07 p <  0.02). It was higher in all obese subjects than in all overweight subjects (7.25 ± 0.64 vs 5.22 ± 0.40 p <  0.01) but the difference between overweight and MHNW was not significant. M was negatively correlated with insulin sensitivity (r =-0.457 p = 0.0008). 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.

Nutritional and metabolic determinants of blood rheology differ between trained and sedentary individuals.

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).

Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients.

OBJECTIVE: To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS: Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS: In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid-reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS: A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Assessment of insulin sensitivity (S I) and glucose effectiveness (S G) from a standardized hyperglucidic breakfast test in type 2 diabetics exhibiting various levels of insulin resistance.

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.

Blood rheology and body composition as determinants of exercise performance in male soccer players.

The aim of this study was to assess on a large series of soccer players our previous reports on blood rheology and exercise performance. In 99 soccer players (Age 24,17 ± 0,42 yr; weight 75,87 ± 0,89 kg; VO2max 46,86 ± 0,95 mL/min/kg) an exercise test was performed for measuring maximal aerobic capacity and we measured blood viscosity at high shear rate (MT90 viscometer) and RBC aggregation (Myrenne MK1). The French questionnaire developped by the consensus group on overtraining of the French Society of Sports Medicine (SFMS) was also employed. The only hemorheologic statistical determinant of VO2max was hematocrit (Hct r = -0.2439; p = 0.0303). The lactate threshold 2 mmol/l was negatively correlated to M1 (r = -0.43224; p = 0.00847). There was a borderline correlation between the overtraining score at the questionnaire of the SFMS and plasma viscosity (r = 0.3080; p = 0.0532). Therefore, our study confirms that aerobic capacity in this sport is negatively correlated to hematocrit, that RBC aggregation is positively associated with blood lactate accumulation in blood during exercise, and that plasma viscosity is one of the parameters that increase when the athlete is on the edge of the overtraining syndrome. These data are consistent with previous reports about soccer players but caution is needed to extrapolate to other sports.

Body composition and exercise performance as determinants of blood rheology in middle-aged patients exhibiting the metabolic syndrome.

Aerobic capacity and performance are associated with increased blood fluidity, while sedentarity leads to decreased exercise performance, and blood hyperviscosity. We aimed at investigating the relationships among body composition, blood rheology and exercise performance in this situation. In 46 sedentary subjects (53.09 ± 1.79 yr old; BMI = 32,35 ± 0,80) attending our unit for an exercise prescription we performed an exercise test to assess aerobic capacity, together with blood lipid profile and blood viscosity (MT 90 viscometer, Myrenne erythroaggregometer). The maximal aerobic capacity VO2max was not correlated to blood rheology but its changes were negatively correlated to those of plasma viscosity (r = -0.679) and pre-training VO2max values were negatively correlated to the BMI (r = -0.45873; p = 0.00430) and fatness (waist circumference r = -0.53476; p = 0.00406). Hemorheological parameters were as expected correlated to blood lipids. The main determinant of the RBC rigidity index Tk was HDL-cholesterol (r = -0.70026; p = 0.00121). The main determinant of M1 is HDL-cholesterol (r = -0.5157; p = 0.0238). RBC aggregability "M" is negatively correlated to total cholesterol (r = -0.758932; p = 0.000105); HDL-cholesterol (r = -0.62232; p = 0.00444); LDL-cholesterol (r = -0.64486; p = 0.00386). Whole blood viscosity is correlated to triglycerides (r = 0.8569; p = 0.00000140) and negatively correlated to HDL-cholesterol (r = -0.5622; p = 0.0122). Waist circumference (an index of abdominal fatness) is correlated to blood viscosity (r = 0.597; p = 0.00888). The waist to hip ratio is correlated to Hct (r = 0.70075 p = 0.00120) and to blood viscosity (r = 0.8124334; p = 0.0000420). Fat-free mass is correlated to blood viscosity (r = 0.66528; p = 0.00137) and hematocrit (r = 0.64350; p = 0.00220). Hip circumference is negatively correlated to plasma viscosity (r = -0.5007; p = 0.0290). Therefore, this study confirms that hemorheological parameters are influenced by blood lipids, that changes in plasma viscosity are correlated to those of aerobic capacity, and that abdominal fat mass is associated with a worsening of blood rheology and of exercise performance. By contrast, gluteal fat (a factor associated with favorable lipid profile and high insulin sensitivity) is associated with a decrease in plasma viscosity, and fat-free mass is associated with higher blood viscosity and hematocrit, consistent with recent literature linking its size in abdominal obesity with a deleterious metabolic profile.

Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations.

CONTEXT: The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). OBJECTIVES: The objectives of the study were to validate the GHRH+Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests. DESIGN: This was a multicenter, randomized, open-label, phase III study. SETTING: The study was conducted at 10 French university hospitals. SUBJECTS: Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH+Arg-GHRH+Arg-ITT test sequence and 34 to the ITT-ITT-GHRH+Arg test sequence. INTERVENTIONS: Each subject underwent three tests of GH secretion separated by 24 h or more. MAIN OUTCOME MEASURES: The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. RESULTS: Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 microg/liter for GHRH+Arg corresponding to 3 microg/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 microg/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH+Arg test was expressed by 74% of subjects. CONCLUSIONS: The GHRH+Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH+Arg test represents a good alternative to the ITT for the diagnosis of AGHD.

Relationship between blood lactate concentration and substrate utilization during exercise in type 2 diabetic postmenopausal women.

Increased blood lactate concentration and alterations of substrate utilization have been shown to be partly involved in development of insulin resistance in obese and type 2 diabetic patients. As blood represents the first great distribution space and participates to lactate exchange in whole body, we investigated lactate transport in red blood cells at rest and the potential relationships between elevated blood lactate and substrate utilization in 7 obese controls and 7 obese type 2 diabetic postmenopausal women during an incremental exercise test. Blood samples were collected at rest, 30%, 50%, and 60% of maximal power and at 8 and 20 minutes of recovery time. Baseline lactatemia and its increase during exercise were higher in the diabetic group (P < .05). We found a negative correlation between basal and 30% maximal power lactatemia and 2 indexes of substrate utilization (crossover point: r = -0.79, r = -0.82 and maximal lipid oxidation point: r = -0.83, r = -0.80; P < .05) in diabetic group only. Furthermore, there were positive correlations between the affinity constant, maximal velocity transport, and basal lactate level in diabetic subjects (r = 0.91 and r = 0.73, respectively; P < .05). These results show that the elevation of blood lactate is associated with a greater carbohydrate oxidation in type 2 diabetes, but the mechanisms underlying the alteration of substrate utilization need to be clarified. Furthermore, increased lactate levels cannot be explained by alterations of lactate transport in red blood cells, but it could affect monocarboxylate transporter 1 properties.