Evaluation of insulin sensitivity and glucose effectiveness during a standardized breakfast test: comparison with the minimal model analysis of an intravenous glucose tolerance test.

There is a need for reliable measurements of insulin sensitivity (SI) simpler than the euglycemic hyperinsulinemic clamp or the intravenous glucose tolerance test (IVGTT), which could be used when the simpler surrogates based on fasting insulin (Ib) and glucose (Gb) lose their validity. Several evaluations of SI derived from oral glucose tolerance test (OGTT) or its physiologic form, the standardized breakfast test (SBT), have been proposed. We aimed at determining which SBT-derived measurements of SI give the best prediction of the values obtained with the minimal model analysis of an IVGTT. Twenty-eight subjects (23 females and 5 males; age, 44.3+/-0.6 years) with a wide range of glucose tolerance randomly underwent a hyperglucidic SBT and an IVGTT with minimal model analysis. Correlations of 35 indices (converted if appropriated into similar units) with IVGTT-derived SI were calculated, and the accuracy of the empiric formulas obtained with the 11 best predictions were evaluated with Bland-Altman plots. Subjects covered all the spectrum of SI between 0.19 and 21.3 min-1/(microU.mL-1)x10(-4). Eight procedures yielded satisfactory predictions of minimal model SI: (1) SI (from Matsuda's composite index)=-1.24+65/(IbGbImGm)-0.5; (2) SI=1.89+2690/(IbGbImGm); (3) SI (from Bennett's index)=-2.93+5.16/(log Ibxlog Gb); (4) SI (from Sluiter's index)=0.2+2400/(IpGp); (5) SI=-8.54+38.4/(Belfiore's ISI index); (6) SI (from Cederholm's formula)=76/(Gm log Im); (7) SI=0.248+0.947/GbIm; (8) SI (from Mari's "oral glucose insulin sensitivity" index)=oral glucose insulin sensitivity/Ip; (9) Caumo's model. Glucose effectiveness Sg can also be accurately predicted by the following formula: Sg=2.921e-0.185(G60- Gb) (Ip=insulin peak; Gp=glucose peak; Ia=insulin area; Ga=glucose area; G60=glycemia at 60 minutes). The hyperglucidic SBT can provide accurate evaluations of SI and Sg, either by elaborated models or by simple empiric formulas.

The hemorheological aspects of the metabolic syndrome are a combination of separate effects of insulin resistance, hyperinsulinemia and adiposity.

The metabolic syndrome which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated, contributing to a various extent to a global impairment of blood rheology. We previously reported in 157 nondiabetic subjects that both obesity and insulin resistance increase red cell rigidity (Dintenfass's Tk) and plasma viscosity (eta p), and that whole blood viscosity at high shear rate (eta b 1000 s(-1)) reflects rather obesity than insulin resistance. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 81 subjects into 4 subgroups according to quartiles of insulin sensitivity (SI) (measured with the minimal model of an intravenous glucose tolerance test) and baseline insulin. Results show that (1) values of SI within the upper quartile are associated with low eta b due to low eta p; (2) low SI regardless insulinemia is associated with increased aggregation indexes; (3) when low SI is associated with hyperinsulinemia (insulin the upper quartile and SI in the lower) there is a further increase in eta b due to an increase in eta p; (4) neither SI nor insulinemia modify Hct. Thus hyperinsulinemia and insulin resistance induce hyperviscosity syndromes which are somewhat different, although they are associated most of the time. Low SI increases RBC aggregation while hyperinsulinemia increases eta p.

Hemorheological disturbances correlate with the lipid profile but not with the NCEP-ATPIII score of the metabolic syndrome.

The metabolic syndrome, which is associated with an high risk for diabetes and atherothrombosis, is associated with hemorheologic abnormalities. These abnormalities seem more and more to be explained by its various symptoms than by insulin resistance which represents theoretically the core of the syndrome. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 90 subjects into 4 subgroups according to the clinical score "NCEP-ATPIII" which is the best recognized standardized definition of the syndrome. Results show no significant changes of blood rheology across classes of NCEP score despite a borderline rank correlation between RBC aggregability "M1" and the score. Whole blood viscosity was mostly correlated to HDL-cholesterol (r = -0.353, p = 0.007) and triglycerides (r = 0.574, p = 0.0001). Plasma viscosity was correlated with total cholesterol (r = 0.3359, p = 0.02) and with LDL-cholesterol (r = 0.357, p = 0.03). Red blood cell rigidity "Tk" was negatively correlated to HDL-cholesterol (r = -0.430, p = 0.007). Aggregability "M" was correlated to total cholesterol (r = 0.356, p = 0.01) and "M1" to HDL-cholesterol (r = -0.406, p = 0.006). Thus, despite previously described correlations with glucose disposal parameters, the hyperviscosity syndrome of the metabolic syndrome is not proportional to its clinical scoring and is strongly dependent upon the lipid profile.

Partially opposite hemorheological effects of aging and training at middle age.

Aging impairs blood rheology while various training protocols improve it. The purpose of this study was to delineate the respective role of aging and endurance training on blood rheology. Thirty-two subjects [16 middle-aged men: 8 cyclists (MAcy) and 8 sedentary men (MAsed) and 16 young men: 8 cyclists (Ycy) and 8 sedentary men (Ysed)] were compared in this study. Results showed higher red blood cell (RBC) rigidity and aggregability (AFFIBIO), lower RBC disaggregability (AFFIBIO) at middle age than at 25 yr, regardless of training status. However there was no age-related difference in whole blood viscosity at either native or corrected hematocrit, plasma viscosity, hematocrit, and Myrenne aggregation indexes M and M1. Training was associated with a reduced hematocrit in middle age subjects but not in 25 yr old ones. We evidenced no effect of training on red cell rigidity (Dintenfass's Tk index), in whole blood viscosity at either native or corrected hematocrit, and plasma viscosity. Thus, regular cycling at middle age maintains a low hematocrit but does not prevent aging-related increase in red cell rigidity and aggregability. Specific effects of cycling among other sports may explain this specific pattern.

Hemorheologic effects of low intensity endurance training in sedentary patients suffering from the metabolic syndrome.

Hemorheologic effects of exercise training ("hemorheologic fitness") are very different according to the mode and the intensity of this training. We previously reported that low intensity endurance training in sedentary patients suffering from the metabolic syndrome sumultaneously improved blood rheology, body composition and lipid oxidation at exercise. We aimed at analyzing the link among these improvements in 24 patients submitted to a 2 months targeted training designed for increasing exercise lipid oxidation. Variations of whole blood viscosity at high shear rate (etab 1000 s(-1)) were explained here by two statistically independent determinants: hematocrit and red cell rigidity. etab decreased in 16 subjects, but increased in 8, due to a rise in hematocrit. Changes in RBC rigidity appeared to reflect weight loss and decrease in LDL cholesterol. Plasma viscosity was related to cholesterol and its training-induced changes are related to those of VO2 max ) but not to lipid oxidation. Red cell aggregability (Myrenne) reflected both the circulating lipids (Chol, HDL and LDL) and the ability to oxidize lipids at exercise. Factors associated to a post-training decrease in aggregability (M1) were weight loss and more precisely decrease in fat mass, improvement in lipid oxidation, rise in HDL-Chol, and decrease in fibrinogen. On the whole the major determinant of hemorheologic improvement was an increase in cardiorespiratory fitness (VO2 max ), correlated with a decrease in plasma viscosity, rather than an improvement in lipid metabolism, although RBC aggregability and deformability exhibited clear relationships with lipid metabolism. For which reason Hct increased in 30% of the patients during this kind of training remains unclear.

Hemorheological aspects of the metabolic syndrome: markers of insulin resistance, obesity or hyperinsulinemia?

The metabolic syndrome is a major health problem in western countries, due to the deleterious metabolic consequences of sedentarity and rich diet in the large part of the population who exhibits the so-called "thrifty phenotype". This syndrome, which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the respective importance of each of these factors. Subjects were divided in 6 groups according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4), highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that whole blood viscosity at high shear rate is higher in obese subjects (p<0.01). Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012 (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The aggregability index "M1" is increased when SI<1.1 in both obese and nonobese subjects. No clear effect of either SI or obesity on hematocrit is observed. On the whole, obesity and insulin resistance both impair blood rheology by acting on red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the metabolic syndrome is far to be only a reflect of insulin resistance alone.

Type 2 diabetics with higher plasma viscosity exhibit a higher blood pressure.

Among hemorheologic parameters, plasma viscosity is one of the most studied in epidemiology, so that it has emerged as an independent risk factor. In diabetes, plasma viscosity is frequently elevated. For this reason we tried to define characteristics of non-insulin dependent diabetics with high plasma viscosity (>1.45 mPa.s) and whether they were more insulin resistant and/or exhibited other hemorheologic disturbances. 12 subjects (age 56.1+/-11.7; BMI 28.6+/-4.8) were thus found to have a value of plasma viscosity >1.45 mPa.s. They were compared to 20 age and BMI-matched NIDDMs. Patients have similar insulin sensitivity, HbA1c, and fibrinogen. RBC aggregation, rigidity and hematocrit were not significantly different. Whole blood viscosity at high shear rate was slightly higher (p=0.05). When corrected for hematocrit whole blood viscosity is no longer different. However, hematocrit was not lower in subjects with hpl >1.45. By contrast blood pressure was markedly higher (systolic: 177.5+/-2.5 mmHg vs 140+/-8 mmHg, p<10(-8); diastolic 110+/-14 vs 83+/-9 mmHg, p<10(-9); mean 132+/-18 mmHg vs 102+/-7 mmHg p<10(-9)). Therefore, in NIDDM, higher plasma viscosity, regardless insulin resistance and adiposity, is strongly related to blood pressure.

Hemorheological alterations related to training and overtraining.

Alterations of blood rheology related to muscular activity have been extensively studied over the last 20 years. It has been shown that exercise exerts a "triphasic" action on the rheological properties of blood. In the short term, exercise induces a transient hyperviscosity, mostly due to a rise in hematocrit and plasma viscosity, but also to alterations in erythrocyte rheology. Reversal of this hyperviscosity pattern over the following 24 h can be described as an "autohemodilution". Later, training results in several profiles of "hemorheologic fitness" with a low hematocrit reflecting an expansion in plasma volume, and improvements in red cell rheology (increased deformability, decreased aggregation, reduced disaggregation shear rate). Some specific aspects of these long-term adaptations have been described, such as the intriguing occurrence of a paradoxical improvement in RBC deformability during exercise in some athletes, and overtraining, which is associated with higher plasma viscosity. Given the variety of modes of exercise and the wide heterogeneity of their effects on blood rheology in the short and long term, many investigations remain to be performed in this area of clinical hemorheology.

Prediction of hematocrit and red cell deformability with whole body biological impedance.

Bioelectrical impedancemetry has been used to evaluate hemorheological parameters in vitro but whole body impedance measurements are also correlated to some hemorheologic factors, due to their close relationship with determinants of electric properties of blood. In previous studies, we have determined a set of predictive equations for hematocrit, whole blood viscosity and plasma viscosity in both sedentary and trained individuals. In this study we aimed at verifying those findings and investigating for other equations in a sample of 62 subjects whose body composition was assessed with a multifrequency bioelectrical impedancemeter using low intensity at the following frequencies: 1, 5, 10, 50 and 100kHz. Viscometric measurements were done with a falling ball viscometer. Hematocrit was measured with microcentrifuge. We confirm that hematocrit was correlated with impedance measurements at 50 kHz (r=-0.671, p < 0.01), and describe a new predictive equation for RBC rigidity index "k" calculated with the equation of Quemada, ("k" index = 0.0003 Z50 + 1.2815; mean difference: -0.0506; 95% confidence interval of -0.0134 to 0.00324) that is also correlated with impedance measurements at 50 kHz (r = 0.526, p < 0.01). Although the precision of these formulae is not sufficient for allowing true "predictions" of hematocrit and red cell deformability, these findings confirm that factors of viscosity are to some extent reflected by whole body electric properties.