Increased hepatic efficacy of urea synthesis from alanine in insulin‐dependent diabetes mellitus

Abstract
The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin‐dependent diabetes mellitus (HbAlc = 8.4±1.0% (mean±SD)).Following an overnight fast alanine was infused at 2 mmol h−1 kg−1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations.Fasting glucagon concentrations were 85 + 26 ng 1−1 in controls and 161 ±35 ng 1−1 (P−1 in controls and 44.7±12.41 h−1 (Pr2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54).In conclusion the kinetics of urea synthesis in insulin‐dependent diabetes is changed in favour of increased conversion of alanine‐N to urea‐N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia.