INCREASED PLASMA-LEVELS OF ENDOTHELIN IN DIABETIC-PATIENTS WITH HYPERTENSION

In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8:00 AM under resting conditions and endothelin was measured after prior extraction by a sensitive radioimmunoassay specific for both endothelin 1 and 2. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls. In type 1 diabetes mellitus a positive correlation between endothelin levels and age was found. We found that 60% of patients with type 1 diabetes mellitus and elevated endothelin levels higher than 2.5 pg/mL (highest value in a control person) had had diabetes for more than 20 years (P < .05 v patients with normal endothelin levels). In type 2 diabetes mellitus the relation between elevated endothelin levels and diabetes duration was reversed. Glycosylated hemoglobin (HbA1) concentrations above 10% of total hemoglobin were measured in 62% of the patients. Arterial hypertension was present in 60% of the patients with type 1 diabetes mellitus and increased endothelin levels > 2.5 pg/mL (both P < .05 v patients with normal endothelin levels). A reduced creatinine clearance (< 60 mL/min) was detected in 30% of the patients with type 1 diabetes mellitus with elevated endothelin levels > 2.5 pg/mL, but only in 7% of the patients with endothelin levels < 2.5 pg/mL (P < .05). In patients with type 2 diabetes mellitus the relationship between endothelin and their clinical characteristics was less clear than in patients with type 1 diabetes mellitus. Neither in type 1 nor in type 2 diabetes mellitus did we find endothelin levels related to microalbuminuria as a marker of glomerular damage in diabetic nephropathy. In diabetes mellitus, elevated endothelin levels act at least as a marker or may even play a pathophysiological role in the development of hypertension and its sequelae, but are not markers of diabetic nephropathy. On the other hand, normal endothelin levels in patients with normal HbA1 concentrations are in keeping with the assumption that normalization of blood glucose may reduce the risk of diabetic complications.