Sarah C Skinner1,2, Mor Diaw3, Vincent Pialoux1,2,4, Maïmouna Ndour Mbaye5, Pauline Mury1,2, Philomène Lopez6, Delphine Bousquet7, Fatou Gueye6, Demba Diedhiou5, Philippe Joly1,2,8, Céline Renoux1,2,8, Djiby Sow5, Saliou Diop9, Brigitte Ranque2,10, Agnès Vinet11, Abdoulaye Samb3, Nicolas Guillot7, Philippe Connes12,2,4. 1. Inter-university Laboratory of Biology of Motor Function EA7424, Vascular Biology and the Red Blood Cell Team, Claude Bernard University Lyon 1, University de Lyon 1, Villeurbanne, France. 2. Laboratory of Excellence GR-EX, Paris, France. 3. Laboratory of Physiology and Functional Exploration, Faculté de Medecine de Pharmacie et d'Odontologie, Université Cheikh Anta Diop de Dakar, Dakar, Senegal. 4. Institute of Universities of France, Paris, France. 5. Medical Clinic II, Abass Ndao Hospital Center, Dakar, Senegal. 6. Laboratory of Pharmaceutical Biochemistry, Faculté de Medecine de Pharmacie et d'Odontologie, Université Cheikh Anta Diop de Dakar, Dakar, Senegal. 7. CarMeN Laboratory, INSERM 1060, Institut National des Sciences Appliquées 1397, Université Claude Bernard Lyon 1, Institut National des Sciences Appliquées Lyon, Villeurbanne, France. 8. Laboratory of Biochemistry of Erythrocyte Pathologies, Biology Center East, Bron, France. 9. Laboratory of Hemato-Immunology, Faculté de Medecine de Pharmacie et d'Odontologie, Université Cheikh Anta Diop de Dakar, Dakar, Senegal. 10. INSERM, UMR_S970, Paris Descartes University, Sorbonne Paris Cité, Paris, France. 11. Laboratoire de Pharm-Ecologie Cardiovasculaire, Université d'Avignon, Avignon, France. 12. Inter-university Laboratory of Biology of Motor Function EA7424, Vascular Biology and the Red Blood Cell Team, Claude Bernard University Lyon 1, University de Lyon 1, Villeurbanne, France pconnes@yahoo.fr.
Abstract
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.
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.
Authors: Anna Cronin de Chavez; Karl M Atkin; Fiona Babbington; Maria J Berghs; Simon M Dyson; Adrian Miller; Donald C Whitelaw Journal: Clin Diabetes Date: 2020-01