ROLE OF ELEVATED ENDOTHELIN LEVELS FOR THE DEVELOPMENT OF DIABETIC COMPLICATIONS

In order to gain insight into the potential role of endothelin, a 21 a mino acid peptide produced by endothelial cells, in die development of complications of diabetes mellitus, basal plasma endothelin levels we re measured in 152 patients with diabetes mellitus (83 patients with t ype 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) an d compared to those in 50 healthy controls. Blood was drawn at 8.00 a. m. under resting conditions and endothelin was determined after prior extraction by a sensitive radioimmunoassay. Endothelin levels were inc reased in patients with diabetes mellitus in comparison to controls (c ontrols 0.9 +/- 0.1 pg/ml, type 1 diabetes mellitus 1.7 +/- 0.1, type- 2-diabetes mellitus 2.0 +/- 0.1 pg/ml, p < 0.01 vs controls). 60% of p atients with type 1 diabetes mellitus and elevated endothelin levels > 2.5 pg/ml (highest value measured in a control subject) had arterial hypertension with blood pressure > 140/90 nun Hg (p < 0.05 vs patients with normal endothelin levels). A reduced creatinine clearance (< 60 ml/min) was detected in 30% of patients with type 1 diabetes mellitus with elevated endothelin levels > 2.5 pg/ml, but only in 7% of patient s with endothelin levels < 2.5 pg/ml (p < 0.05). In patients with type 1 diabetes mellitus and elevated endothelin levels diabetic retinopat hy and peripheral neuropathy (p < 0.05) were more prevalent than in pa tients with normal endothelin values. 62% of patients with elevated en dothelin levels had insufficient metabolic control (HbA1 concentration s above 10%). Positive correlations were found between endothelin and human atrial natriuretic peptide levels. The relationship between endo thelin and clinical characteristics of the patients was less clear in type 2 diabetes mellitus than in type 1 diabetes mellitus. In diabetes mellitus, elevated endothelin levels may act at least as an indicator or even play an important part in the disease mechanisms of developin g diabetic complications. On the other hand, normal endothelin levels as measured in patients with normal HbA1 concentrations might contribu te to the prevention of diabetic complications.