Plasma endothelin-1 (ET-1) levels as merker of retinopathy (DR) in NIDDM patients

Purpose: Diabetic microvascular and macrovascular alterations frequently cause retinopathy. Takahashi reported increased levels of Endothelin-1 (ET-1), vasoconstrictive peptide produced by endothelial cells, in NIDDM patients suggesting that ET-1 may play a role in diabetic vascular complications. A direct correlation between Von Willebrand factor and proliferative retinopathy in association with higher levels of ET-1 were reported from Morise. We evaluated ET-1 plasma levels in different degrees of diabetic retinopathy and analyzed the relationships between ET-1 levels and retinal damage. Methods: We studied 16 NIDDM, and 16 age-matched control subjects. Exclusion Criteria were: F.B.G. >7.7 mmol/L, HbA1c > 7%, glycosurie, B.P. >150/90 mmHg, clinical signs of macrovascular damage, microalbuminuria, refractive error >±2D and I.O.P.> 20 mmHg. Ophthalmological assay was related to classify degree of Retinopathy according to Klein. Assessment of ET-1 plasma levels was performed with reverse phase HPLC followed by RIA evaluation. Results: 6 patients (37,5%) did not show any retinal change in both eyes, while 10 patients (62,5%) in at least one eye, presented DR. Resulting data showedsignificantly (p<0.001) higher levels of plasma ET-1 in NIDDM patients (0.80±0.13 pg/mL) than in controls (0.60±0.12 pg/ml). Plasma ET-1 levels resulted directly related to retinopathy scores in NIDDM patients (n=10; r=0.368; p=0.02); those levels were significantly higher (p<0.05) in patients with retinopathy (0.89±0.13 Vs.pg/mL) than in those without (n=6; 0.71±0.19 pg/mL). Discussion: Retinopathy in NIDDM patients is associated with increased levels of plasma endothelin-1. ET-1 may be produced in response to several conditions hypoxia, hyperinsulinism and hyperglycemia ecc. This can induce an endothelial cell damage, determining increase of ET-1 secretion and subsequently imbalance in retinal metabolic needs and ocular blood flow. Our data demonstrated a significant correlation between ET-1 levels and retinopathy degree. Increased ET-1 levels could be responsible for retinopathy development and progression but, in our opinion, it represent a marker of such diabetes related complication.