Abstract
[N(ε)-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 · kg-1 · 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 [N(ε)-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 116-120 |
| Number of pages | 5 |
| Journal | Diabetologia |
| Volume | 41 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1998 |
| Externally published | Yes |
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Keywords
- Acylated insulin
- Glucose turnover
- Insulin
- Insulin therapy
- NPH
- Pharmacokinetics
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM. / Radziuk, J.; Pye, S.; Bradley, B.; Braaten, J.; Vignati, L.; Roach, Paris; Bowsher, R.; DiMarchi, R.; Chance, R.
In: Diabetologia, Vol. 41, No. 1, 1998, p. 116-120.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM
AU - Radziuk, J.
AU - Pye, S.
AU - Bradley, B.
AU - Braaten, J.
AU - Vignati, L.
AU - Roach, Paris
AU - Bowsher, R.
AU - DiMarchi, R.
AU - Chance, R.
PY - 1998
Y1 - 1998
N2 - [N(ε)-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 · kg-1 · 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 [N(ε)-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.
AB - [N(ε)-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 · kg-1 · 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 [N(ε)-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.
KW - Acylated insulin
KW - Glucose turnover
KW - Insulin
KW - Insulin therapy
KW - NPH
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=0031930095&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031930095&partnerID=8YFLogxK
U2 - 10.1007/s001250050876
DO - 10.1007/s001250050876
M3 - Article
C2 - 9498640
AN - SCOPUS:0031930095
VL - 41
SP - 116
EP - 120
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 1
ER -