BASAL ACTIVITY PROFILES OF NPH AND [N-EPSILON-PALMITOYL LYS (B29)] HUMAN INSULINS IN SUBJECTS WITH IDDM

[N-epsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified ins ulin when infused intravenously (i.v.) secondary to its binding to cir culating albumin. The duration and activity profile of the activated ( A) and NPH (B) insulins were assessed following subcutaneous (s.c.) do ses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 3 subjects with IDDM. After overnight i.v. infusion of regular human in sulin, morning glucose was (A) 6.9 +/- 0.1 and (B) 6.8 +/- 0.1 mmol/l. After the s.c. injection, i.v. human insulin or glucose was infused t o maintain near-basal glycaemia and tracer glucose to assess hepatic g lucose production (HGP). An activity profile was deduced for each stud y by expressing the glucose infusion rate at each time point, as a fra ction (%) of the basal (measured) HGP, and the i.v. insulin infusion r ate as a fraction (%) of the basal requirement, The two fractions are combined by adding the fractional glucose infusion rate and subtractin g the fractional insulin infusion rate. Infusion rates of i.v. insulin in the morning were (A) 0.96 +/- 0.096 and (B) 1.22 +/- 0.09 pmol.kg( -1).min(-1). After insulin injection, i.v insulin requirements decreas ed and were below 10 % of basal between 100 and 150 min, A constant ac tivity profile of 0 % represents a perfect substitution of the basal i .v. insulin infusion by the s.c. dose, The actual profile is defined b y deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18 % for [N-epsilon-palmitoyl Lys (B29)] human insulin and 17 +/- 12, 5 +/- 6, -9 +/- 15, 22 +/- 18 % for NPH insulin at 3, 6, 9 and 12 h after s.c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and al the liver.