Basal activity profiles of NPH and [Nepsilon-palmitoyl Lys (B29)] human insulins in subjects with IDDM.
[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s.c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v. infusion of regular human insulin, 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 to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i.v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting 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 x kg(-1) x min(-1). After insulin injection, i.v. insulin requirements decreased and were below 10% of basal between 100 and 150 min. A constant activity profile of 0% represents a perfect substitution of the basal i.v. insulin infusion by the s.c. dose. The actual profile is defined by deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18% for [Nepsilon-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 at the liver.
Radziuk
J
J
Diabetes and Metabolism Research Unit, Ottawa Civic Hospital, ON, Canada.
Pye
S
S
Bradley
B
B
Braaten
J
J
Vignati
L
L
Roach
P
P
Bowsher
R
R
DiMarchi
R
R
Chance
R
R
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005943:Gluconeogenesis / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; C111589:insulin, N(epsilon)-palmitoyl Lys(B29)-; D007336:Insulin, Isophane