Circulating Endothelin-1 in Non-Insulin-Dependent Diabetic Patients with Retinopathy

Abstract

Endothelin-1 (ET-1), a novel 21-amino acid vasoconstrictive peptide secreted by endothelial cells, has been thought to play a role in various forms of vascular disease. Diabetes mellitus is well known for its association with microvascular damage. To investigate whether ET-1 levels may be related to microangiopathy in diabetes mellitus, plasma ET-1 levels were measured in two groups of diabetic patients: A) 47 patients with non-insulin dependent diabetes mellitus (NIDDM) and retinopathy (28 M, 19 F; mean age 60.7+/-8.5 yrs) but without nephropathy (microalbuminuria < 30 mg/day) and hypertension (SBP < 140, DBP < 90 mmHg); group A was divided in three subgroups based on the severity of retinopathy: a) 16 with background retinopathy; b) 21 with pre-proliferative retinopathy; c) 10 with proliferative retinopathy. B) 8 patients with insulin-dependent diabetes mellitus (IDDM) recently diagnosed (6 M, 2 F; 16.4+/-3.8 yrs) without complications. C) 28 healthy subjects (HS) (16 M, 12 F; 47.8+/-11.8 yrs) as controls. In the NIDDM group the ET-1 concentration was significantly higher (17.3+/-2.4 pg/ml) than both in the HS (8+/-4.7 pg/ml) and IDDM patients (10.2+/-3.7 pg/ml) (p < 0.0001). In the subgroups with retinopathy the ET-1 levels were a) 15.1+/-4.3 pg/ml; b) 22.2+/-6.8 pg/ml and c) 16.6+/-5.1 pg/ml. These values were significantly elevated as compared to HS (p<0.001; p < 0.0001; p < 0.002, respectively), being the highest levels of ET-1 observed in the NIDDM patients with pre-proliferative retinopathy. In conclusion our study revealed that the ET-1 concentrations are elevated in NIDDM patients with retinopathy especially in those patients with pre-proliferative retinopathy.

Endothelin-A Receptor Blockade Increases Nutritive Skin Capillary Circulation in Patients with Type 2 Diabetes and Microangiopathy

“…The production and plasma levels of ET-1 are elevated in patients with diabetes, as demonstrated in the present and previous studies [30, 31]. A positive correlation between plasma ET-1 levels and diabetic microangiopathy has been described, suggesting a potential role of the ET system in the pathophysiology of vascular complications of diabetes [30, 32, 33]. We therefore hypothesized that enhanced ET-1-mediated vasoconstriction of precapillary resistance vessels leads to impaired blood flow through nutritive capillaries and increased arteriovenous shunting in patients with type 2 diabetes.…”

Growth Factors in Proliferative Diabetic Retinopathy

“…Alteration of ETs has been demonstrated in both type I and type II diabetes (Bertello et al, 1994;De Mattia et al, 1998;Donatelli et al, 1994;Haak et al, 1992;Kamoi et al, 1994;Kawamura et al, 1992;Laurenti et al, 1997;Letizia et al, 1997;Morise et al, 1995;Takahashi et al, 1990). Although, a number of studies can be cited that provide contradictory reports of plasma ET levels in diabetic patients, it should be noted that these peptides act in both an autocrine and paracrine fashion.…”

Ocular blood flow and associated functional deviations in diabetic retinopathy

“…Increased endothelin-1 plasma concentrations were observed in Type I diabetic patients [218] as well as in Type II patients with diabetic retinopathy [219]. More specifically, it has been shown in immunhistochemical studies that endothelin-1 is increased in retinal tissue of STZ-induced diabetic rats [220] and BB/W rats [221].…”