Sickle Cell Trait Worsens Oxidative Stress, Abnormal Blood Rheology, and Vascular Dysfunction in Type 2 Diabetes

Abstract

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.

Figure 1

Kinetics (log scale) of mean FMD after cuff deflation in patients with diabetes with (T2DM-SCT) or without (T2DM) SCT and of healthy individuals with (SCT) or without (CONT) SCT. SD values are not shown to avoid a cluttered figure. Significant differences between groups: *P < 0.05; ***P < 0.001.

Figure 2

FMD and PWV of patients with diabetes with (T2DM-SCT) or without (T2DM) SCT and of healthy individuals with (SCT) or without (CONT) SCT. FMD measured at 90 s (A), FMD measured at 90 s corrected by shear stress values (B), mean FMD determined over 10 min after cuff deflation (C), and PWV (D) in the different groups. The two extremities of the horizontal bars indicate the difference between two given groups (*P < 0.05; ***P < 0.001). Means ± SD.