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Kathleen Josephine Jee, Brooks Puchner, Syed Junaid Hassan, Mike Dent, Akrit Sodhi; Correlation of Serum Levels of Angiopoietin-like 4 with Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5168.
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© ARVO (1962-2015); The Authors (2016-present)
In the developing world, where the skills and resources needed to diagnose and treat diabetic retinopathy (DR) are scarce, little has been done to prepare for the looming diabetes pandemic. One unmet need is the identification of biomarkers that predict which diabetic patients require ophthalmic care. In this regard, angiopoietin-like 4 (ANGPTL4) is a multi-functional protein whose levels are reported to be altered in diabetic patients. However, the relationship between serum ANGPTL4 and DR has not been explored.
Institutional Review Board approval was obtained from the Johns Hopkins University School of Medicine to collect serum from diabetic and non-diabetic control patients. Serum samples were processed and levels of ANGPTL4 were quantified using ELISA. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, Dunn’s multiple comparison tests, and Spearman correlation.
There was no statistically significant difference in serum levels of ANGPTL4 between diabetic and control patients. This non-relationship persisted with further differentiation of diabetic patients into no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). However, when a subset (68 controls, 50 diabetics) of serum samples was processed at reduced centrifugation speed (as had been used in prior studies), serum ANGPTL4 levels in diabetic patients (21.8 ± 15.5 ng/mL) were significantly increased relative to controls (16.4 ± 16.2 ng/mL; p<0.0001). Patients with PDR (n=17) had increased serum ANGPTL4 concentration (20.2 ± 7.9 ng/mL) relative to controls (16.4 ± 16.2 ng/mL; p<0.01), but the sample size was too small to detect a difference compared to diabetics with NPDR or no DR. Patients with chronic kidney disease (n=8) also had elevated serum ANGPTL4 levels (42.3 ± 28.4 ng/mL) compared to patients without renal disease (n=106; 18.6 ± 16.1 ng/mL; p<0.0001). However, the increase in ANGPTL4 levels in PDR patients was independent of the presence of renal disease.
No relationship was found between serum ANGPTL4 and diabetes or DR status at standard centrifugation speed. However, a reduced centrifugation speed exposed an increase in serum ANGPTL4 in diabetics, including those with PDR. This suggests a potential relationship between serum ANGPTL4 and diabetic eye disease, but also highlights the importance of sample processing in evaluating serum biomarkers.
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