Plasma endothelin-1 and total insulin exposure in diabetes mellitus

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relati onship, and ET-1 effects on vascular wall structure are similar to the long -term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their tota l insulin exposure to see if plasma ET-1 might be a link between insulin ex posure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight gly caemic control for 2 years in a cross-sectional design. We measured basal a nd glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinf old thickness, glomerular filtration rate, albumin excretion rate and stand ard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Typ e II diabetes. Patients with an albumin excretion rate >300 mu g/min were e xcluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 norma l subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in T ype II diabetes (P = 0.0001). In all patients with measurable plasma C-pept ide, plasma ET-1 was associated with basal plasma C-peptide (r = 0.5018, P < 0.0001), with stimulated plasma C-peptide (r = 0.5379, P < 0.0001), and w ith total daily insulin dose (r = 0.2219, P = 0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily in sulin dose. Our study shows that the plasma concentration of ET-1 is closel y associated with insulin secretion and insulin dose in patients with diabe tes. plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Inc reased insulin exposure in patients with diabetes may have long-term effect s on vascular wall structure through its stimulation of ET-1 expression.