Plasma adrenaline kinetics in type 1 (insulin-dependent) diabetic patients with and without autonomic neuropathy

Plasma adrenaline kinetics (clearance, extraction across the forearm, initial plasma disappearance rate, mean sojourn time, volume of distribution) were studied in sixteen Type 1 (insulin-dependent) diabetic patients during constant i.v. infusion of tritium labelled adrenaline. In patients with (n = 8) and without (n = 8) neuropathy forearm venous plasma noradrenaline and adrenaline concentrations as well as plasma clearance of adrenaline based on arterial sampling (1.7 vs 2.1 l/min) were not significantly different. The initial disappearance time (T 1/2) after the infusion of the tritium labelled adrenaline had been stopped was significantly prolonged in Type 1 diabetic patients with neuropathy compared to those without (after 20 min infusion 2.7 vs 2.2 min, p less than 0.02, after 75 min infusion 3.7 vs 2.9 min, p less than 0.05). The corresponding values for the mean sojourn time of adrenaline in plasma were 6.5 vs 4.7 min (p less than 0.05) after 20 min infusion and 18 vs 10 min (p less than 0.05) after 75 min of infusion. The unchanged plasma clearance and the prolonged initial halftime and mean sojourn time of adrenaline in plasma suggest that adrenaline is distributed in a larger volume in Type 1 diabetic patients with neuropathy as compared to patients without neuropathy (estimated space of distribution 29 vs 20 l). Our results suggest that patients with diabetic neuropathy do not adjust the plasma adrenaline concentration to changes in adrenaline infusion rate as rapidly as those without neuropathy, i.e. the effect of an elevated adrenaline secretion rate may be prolonged in patients with diabetic autonomic neuropathy.