Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM

J. Radziuk, S. Pye, B. Bradley, J. Braaten, L. Vignati, Paris Roach, R. Bowsher, R. DiMarchi, R. Chance

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)116-120
Number of pages5
JournalDiabetologia
Volume41
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Insulins
Type 1 Diabetes Mellitus
Insulin
Glucose
Isophane Insulin
Liver
Subcutaneous Injections
Insulin, Regular, Human
Subcutaneous Infusions
Metabolome
Albumins
Fatty Acids

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 journalArticle

Radziuk, J, Pye, S, Bradley, B, Braaten, J, Vignati, L, Roach, P, Bowsher, R, DiMarchi, R & Chance, R 1998, 'Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM', Diabetologia, vol. 41, no. 1, pp. 116-120. https://doi.org/10.1007/s001250050876
Radziuk, J. ; Pye, S. ; Bradley, B. ; Braaten, J. ; Vignati, L. ; Roach, Paris ; Bowsher, R. ; DiMarchi, R. ; Chance, R. / Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM. In: Diabetologia. 1998 ; Vol. 41, No. 1. pp. 116-120.
@article{86b988a029ca4fa7944657c83a7c46d1,
title = "Basal activity profiles of NPH and [N(ε)-palmitoyl Lys (B29)] human insulins in subjects with IDDM",
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.",
keywords = "Acylated insulin, Glucose turnover, Insulin, Insulin therapy, NPH, Pharmacokinetics",
author = "J. Radziuk and S. Pye and B. Bradley and J. Braaten and L. Vignati and Paris Roach and R. Bowsher and R. DiMarchi and R. Chance",
year = "1998",
doi = "10.1007/s001250050876",
language = "English (US)",
volume = "41",
pages = "116--120",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "1",

}

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 -