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Objective: Type 2 diabetes (T2D)-related vascular dysfunction and hemorheological abnormalities could possibly be amplified by sickle cell trait (SCT). These alterations could potentially increase the risk of vascular complications in individuals with combined T2D and SCT. Therefore, this study used a mouse model to determine whether vascular function and blood rheology were more severely altered in combined T2D and SCT than in T2D or SCT alone., Methods: Townes transgenic mice with or without SCT received a 12-week high fat high sucrose or standard diet to create models of combined T2D-SCT, T2D, SCT, and controls. Pressure-induced vasodilation (PIV) and sodium nitroprusside (SNP)-mediated vasodilation in-vivo, and hemorheological parameters were measured., Results: No significant differences in blood viscosity, hematocrit, erythrocyte deformability, or PIV were observed between the control and T2D mice, or the control and SCT mice. However, blood viscosity, erythrocyte deformability, and PIV were significantly altered in the T2D-SCT mice compared to the control mice. There were no differences in SNP response between the groups., Conclusions: Although neither T2D nor SCT alone had significant effects on blood rheology parameters or vascular function, combined T2D-SCT mice had significantly altered blood rheology and significantly impaired vascular function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fasting glucose (FG) and glycated hemoglobin A1c (HbA1c) perform sub-optimally in people of African origin, especially in individuals with sickle-cell trait (SCT). The purpose of this study was to compare the relationships between HbA1c, FG, and fructosamine in individuals from Senegal with and without SCT. HbA1c, FG, and fructosamine were measured in 203 adults from Senegal (100 control: 45 with type 2 diabetes (T2D); 103 SCT: 51 with T2D). Significant, positive correlations were observed between HbA1c and FG, fructosamine and FG, and fructosamine and HbA1c in both groups. The limits of agreement were inappropriately large in both groups for the Bland-Altman plots of HbA1c and FG (control: -95.97 to 83.97%; SCT: -115.9 to 91.52%), fructosamine and FG (control: -100.6 to 99.89%; SCT: -105.6 to 100.6%), and fructosamine and HbA1c (control: -52.03 to 38.98%; SCT: -88.04 to 71.41%). In both groups, the greatest proportion of subjects were considered above the clinical cut-point for hyperglycemia when fructosamine was used as the criterion (control: 33%; SCT: 44.6%), and the lowest percentage of subjects were classified as over the clinical cut-point when HbA1c was used as the criterion (control: 21%; SCT: 27.7%).Substantial disparities between HbA1c, FG, and fructosamine were observed in both groups, and these differences were exaggerated in the SCT group. Therefore, these three biomarkers should not be considered to be interchangeable measures of glycemic control. These biomarkers should be used thoughtfully, and special care should be taken when using them in individuals with SCT., Competing Interests: The authors have declared that no competing interests exist.

Objective: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only., Research Design and Methods: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) ( n = 60), T2D ( n = 52), SCT ( n = 53), and neither T2D nor SCT (control) ( n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured., Results: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this., Conclusions: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension., (© 2018 by the American Diabetes Association.)

Background: Sickle cell trait (SCT) is a benign condition of sickle cell disease. Nevertheless, previous reports showed that SCT carriers have increased blood viscosity and decreased vascular reactivity compared to non-SCT carrier. The benefit of regular exercise on vascular function has been well documented in the general population but no study focused on the SCT population., Purpose: The aim of our study was to compare arterial stiffness and blood viscosity between trained and untrained SCT carriers, as well as a group of untrained non-SCT., Methods: Arterial stiffness (finger-toe pulse wave velocity) and blood viscosity were evaluated in untrained non-SCT carriers (n = 10), untrained SCT carriers (n = 23) and trained SCT carriers (n = 17) who reported at least 10 hours of physical exercise per week., Results: Untrained SCT carriers had higher pulse wave velocity (p = 0.032) and blood viscosity (p < 0.001) than their trained counterparts. In addition, untrained SCT carriers had higher blood viscosity (p < 0.001) than the untrained non-SCT group. A positive association was noted between blood viscosity and pulse wave velocity in the whole study population., Conclusion: Our study suggests that regular exercise may be beneficial for the vascular function of SCT carriers.

Sickle cell trait (SCT) is the benign condition of sickle cell disease. Often asymptomatic, the carriers of the sickle cell trait have hemorheological disturbances with increased oxidative stress compared to healthy subjects. These disturbances can lead to structural and functional changes in large vessels. The aim of the study was to measure arterial stiffness, an independent marker of subclinical atherosclerosis, SCT carriers compared to sickle cell anemia (SCA) subjects. Nine SCT carriers aged 32±9 years (7 men) were compared to 14 SCA subjects aged 29±9 years (2 men) and 22 control subjects aged 34±9 years (11 men) recruited by the National blood transfusion center (CNTS) in Dakar (Senegal). Arterial stiffness was assessed by measurement of the finger-toe pulse wave velocity (PWVft) using pOpmètre ® (Axelife SAS-France). The cardiovascular risk (CVR) was assessed according to the Framingham Laurier score. The SCT carriers had a higher PWVft (m/s) than SCA subjects (8.2±2.2 vs 6.1±0.9m/s, P=0.004) but not different from that of healthy controls (8.2±2.2 vs 7.4±1.8m/s, P=0.33). Linear regression showed a positive relationship between PWVft and the pulse pressure (PP) (P˂0.001; r 2 =0.39; F=13.20). The results show that the SCT carriers have stiffer arteries than SCA subjects. Linear regressions adjusted for age, mean arterial pressure (MAP) and PP, showed that only age and PP were independently correlated with arterial stiffness in the entire population., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: It is predicted that Africa will have the greatest increase in the number of patients with type 2 diabetes mellitus (T2DM) within the next decade. T2DM patients are at risk for cardiovascular disorders. In Sub-Saharan African countries, sickle cell trait (SCT) is frequent. Despite the presence of modest abnormalities in hemorheology and oxidative stress, SCT is generally considered a benign condition. Little is known about vascular function in SCT, although recent studies demonstrated an increased risk of cardiovascular disorders, including venous thromboembolism, stroke, and chronic kidney disease. We hypothesized that SCT could accentuate the vascular dysfunction observed in T2DM., Research Design and Methods: The current study, conducted in Senegal, compared vascular function, hemorheological profile, and biomarkers of oxidative stress, inflammation, and nitric oxide metabolism in healthy individuals (CONT), subjects with T2DM or SCT, and patients with both T2DM and SCT (T2DM-SCT)., Results: Flow-mediated dilation was blunted in individuals with T2DM, SCT, and T2DM-SCT compared with CONT, with vascular dysfunction being most pronounced in the latter group. Carotid-femoral pulse wave velocity measurements demonstrated increased arterial stiffness in T2DM-SCT. Oxidative stress, advanced glycation end products, and inflammation (interleukin-1β) were greater in patients with T2DM-SCT compared with the other groups. Blood viscosity was higher in individuals with TD2M, SCT carriers, and individuals with T2DM-SCT, and the values were further increased in the latter group., Conclusions: Our results demonstrate severe biological abnormalities and marked vascular dysfunction in patients with both T2DM and SCT. SCT should be viewed as a risk factor for further cardiovascular disorders in individuals with T2DM., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group before and after a soccer game performed in two conditions: one with water offered ad libitum (hydration condition; Hyd) and the other one without water (dehydration condition; Dehyd). Blood viscosity and haematocrit per blood viscosity ratio (HVR; an index of red blood cell oxygen transport effectiveness) were measured before and at the end of each game. Resting blood viscosity was greater in the SCT carriers than in the Cont group. The increase of blood viscosity over baseline at the end of the game in the Cont group was similar in the two conditions. In contrast, the change in blood viscosity occurring in SCT carriers during soccer games was dependant on the experimental condition: (1) in Dehyd condition, blood viscosity rose over baseline; (2) in Hyd condition, blood viscosity decreased below resting level reaching Cont values. The Cont group had higher HVR than SCT carriers at rest. HVR remained unchanged in the Cont group at the end of the games, whatever the experimental condition. Although HVR of SCT carriers decreased below baseline at the end of the game performed in Dehyd condition, it increased over resting level in Hyd condition reaching the values of the Cont group. Our study demonstrated that ad libitum hydration in exercising SCT carriers normalises the blood hyperviscosity.

The goal of the present study was to test whether fasting during the holy period of Ramadan may disturb blood rheology in sickle cell trait (SCT) carriers more than in a group of subjects with normal hemoglobin. Twenty African male students participated in the study: 10 SCT carriers and 10 subjects with normal hemoglobin (CONT). Biochemical parameters (plasma glucose and lipids levels), hematocrit, blood viscosity, and urine specific gravity were measured in the two groups on the 14th day of the Ramadan period (Ramadan condition) and 6 wks after the end of Ramadan (baseline condition). All the measurements were performed twice for each experimental day to measure intraday variation: 8:00 and 18:00 h. Plasma glucose level and lipid profile were not significantly different between the two groups. Although Ramadan did not affect the lipid profile, the plasma glucose concentration was lower during the Ramadan period compared with the baseline condition in the two groups. Hematocrit and urine specific gravity did not differ between the two groups and was greater in the evening than in the morning, independently of the condition. SCT carriers had higher blood viscosity than the CONT group. However, whereas blood viscosity remained unchanged through the day in the CONT group, whatever the condition, SCT carriers were characterized by a large increase of blood viscosity in the evening during the Ramadan period, indicating higher risk for microcirculatory blood flow impairments. Specific medical recommendations are needed for SCT carriers engaged in religious fasting.

This study compared erythrocyte changes between a group of subjects with sickle cell trait (SCT) and controls (subjects without hemoglobinopathy) during a soccer game in two conditions: with and without hydration. Erythrocyte deformability of subjects was assessed by the coefficient of erythrocyte rigidity (Tk) which was calculated before and after football match. Our results showed a significant increase in erythrocyte rigidity (Tk) in SCT at the end of physical activities without hydration; however when water was provided ad libitum their Tk decreased significantly, reaching values of controls. And adequate hydration is recommended in subjects with sickle cell trait during and after exercise.

This review presents the epidemiological data regarding the exercise-related complication in exercising sickle cell trait carriers, and focuses on the different potential mechanisms that could be involved in these adverse events, such as hemorheological alterations, inflammation, vascular adhesion of circulating blood cells, oxidative stress and impaired nitric oxide metabolism. We also discuss the effects of different modulating factors such as vascular function, environment (hot temperature), hydration status, physical fitness, exercise intensity and genetic factors.

This study compared the hemorheological responses of a group of sickle cell trait (SCT) carriers with those of a control (Cont) group in response to 40 min of submaximal exercise (exercise intensity, 55% aerobic peak power) performed in two conditions: one with water offered ad libitum, i.e., the hydration (Hyd) condition, and one without water, i.e., the dehydration (Dehyd) condition. Blood and plasma viscosities, as well as red blood cell rigidity, were determined at rest, at the end of exercise, and at 2 h recovery with a cone plate viscometer at high shear rate and 37 degrees C. The SCT and Cont groups lost 1 +/- 0.7 and 1.6 +/- 0.6 kg of body weight, respectively, in the Dehyd condition, indicating a significant effect of water deprivation compared with the Hyd condition, in which body weight remained unchanged. Plasma viscosity increased with exercise and returned to baseline during recovery independently of the group and condition. As previously demonstrated, resting blood viscosity was greater in the SCT carriers than in the Cont group. Blood viscosity increased by the end of exercise and returned to baseline at 2 h recovery in the Cont group in both conditions. The blood viscosity of SCT carriers did not change in response to exercise in the Dehyd condition and remained elevated at 2 h recovery. This extended hyperviscosity, in association with other biological changes induced by exercise, could be considered as a risk factor for exercise-related events in SCT carriers, similar to vasoocclusive crises, notably during the recovery. In contrast, the Hyd condition normalized the hyperviscosity and red blood cell rigidity of the SCT carriers, with blood viscosity values reaching the same lower values as those found in the Cont group during the recovery. Adequate hydration of SCT carriers should be strongly promoted to reduce the clinical risk associated with potential hyperviscosity complications.

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