Abstract
Purpose :
Sub-Saharan Africa faces an epidemic of diabetes. We performed a case-control study of endothelial function nested within a larger prospective cohort study of diabetic retinopathy in Southern Malawi. We report serum levels of endothelial biomarkers and in vivo endothelial function and relationships with progression of retinopathy and mortality.
Methods :
Subjects for the main cohort study were systematically sampled from two hospital-based diabetes clinics. Endothelial function was studied in a subset of subjects in 4 groups: (1) subjects with diabetes and sight threatening diabetic retinopathy (STDR) at baseline, (2) subjects with diabetes and diabetic retinopathy but without STDR, (3) subjects with diabetes but without retinopathy, (4) subjects without diabetes (recruited from spouses of patients attending the diabetes clinics). Clinical examination and biochemical testing was performed to assess HbA1c, BP, HIV status, and serum levels of VEGF, sVCAM-1, sICAM-1, E-selectin and CRP. In vivo endothelial function was assessed using digital pulse amplitude tonometry. Retinopathy was graded with modified Wisconsin grading using 4-field mydriatic photography.
Results :
Endothelial function at baseline was studied in 179 subjects. A fitted multiple linear regression model showed a significant difference in mean serum VEGF between subjects with and without diabetes but not between subjects with and without diabetic retinopathy or between subjects with and without STDR. Serum level of VEGF and E-selectin was associated with presence of diabetes in multiple logistic regression. Endothelial function was also investigated in relation to progression of retinopathy and mortality at 24 months. Two (or more) step progression on the Liverpool Diabetic Eye Study scale was observed in 24 subjects (19.2%; 12.3-26.1 95% CI). Neither VEGF, ICAM-1, E-selectin, VCAM-1, CRP or peripheral artery tonometry index at baseline were associated with progression of retinopathy. Serum VCAM-1 was associated with death in multivariate regression.
Conclusions :
This study provides the first evidence from sub-Saharan Africa of endothelial dysfunction in subjects with diabetes and of an association between levels of endothelial biomarkers and mortality in these subjects. No difference was observed in endothelial biomarkers between subjects in whom retinopathy progressed and those in whom it did not.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.