Patients With T2D and Sickle-Cell Trait at Higher Risk for Complications

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Sickle-cell trait is the heterozygous form of sickle-cell anemia that has long been considered benign; recent evidence, though, indicates it may cause negative health effects.
Sickle-cell trait is the heterozygous form of sickle-cell anemia that has long been considered benign; recent evidence, though, indicates it may cause negative health effects.

According to study results published in Diabetes Care, patients with both sickle-cell trait (SCT) and type 2 diabetes (T2D) experience more frequent diabetes-related complications, including hypertension, diabetic retinopathy, and decreased renal function, compared with patients with only T2D.

Though SCT has historically been considered benign, recent evidence has indicated that SCT may alter blood rheology and increase coagulation activity and risk for stroke and renal disease. The investigators of this study sought to determine whether SCT increases the prevalence of T2D-related complications in individuals with combined T2D and SCT compared with individuals with T2D alone.

The study population included 221 individuals recruited from the National Center of Blood Transfusion and the Diabetic Center at the Hospital Abass Ndao in Senagal, as well as the general population of Dakar. Of 221 individuals, 60 participants had combined SCT and T2D, 52 participants had only T2D, 53 participants had only SCT, and 56 were healthy controls. The presence of retinopathy, peripheral neuropathy, peripheral artery disease, impaired renal function, and hypertension indicated diabetic complications. In addition, patients were screened for arterial stiffness, blood rheology and viscosity measures, and levels of plasma advanced glycation end products (AGEs), compounds that increase with hyperglycemia and may promote the progression of diabetic complications.

AGE receptor interaction can upregulate the transcription of E-selectin, an inflammatory protein secreted from endothelial cells associated with cardiovascular disease in T2D. Expression of inflammatory and adhesion factors was measured in participants' aortic endothelial cells after incubation with plasma. Specifically, the researchers aimed to evaluate the impact of AGE inhibition on human aortic endothelial cell expression of E-selectin.

Retinopathy, hypertension, and renal function impairment were significantly more prevalent in the group with T2D and SCT compared with the other study groups. In addition, the group with T2D and SCT had higher shear rates of blood viscosity, thixotropic index, and arterial stiffness. In multivariable analysis, a significant association was found between AGE accumulation and arterial stiffness. After incubation with plasma, E-selectin expression was higher in the group with T2D and SCT than the other groups. Moreover, when AGE formation was inhibited, aortic endothelial cell expression of E-selectin significantly decreased.

The researchers suggested future studies include participants outside of Senegal, as SCT is not only prevalent in Sub-Saharan Africa but also in populations in the United States, Middle East, and India.

Overall, diabetic complications were more prevalent in patients with both SCT and T2D than in patients with T2D alone; the presence of SCT may further exacerbate vascular complications, including arterial stiffness and blood viscosity. The investigators concluded that patients with a combination of SCT and T2D should be monitored more closely for these complications.

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Reference                    

Skinner SC, Diaw M, Pialoux V, et al. Increased prevalence of type 2 diabetes-related complications in combined type 2 diabetes and sickle cell trait [published online October 16, 2018]. Diabetes Care. doi:10.2337/dc18-1289

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