Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes

Najya Attia, Sonia Caprio, Timothy W. Jones, Rubina Heptulla, John Holcombe, David Silver, Robert S. Sherwin, William V. Tamborlane

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

To determine the effect of acute insulin withdrawal and its subsequent replacement on components of the insulin-like growth factor (IGF)-1 binding protein system and on circulating leptin levels in patients with type 1 diabetes. Seventeen patients (age 31 yr ± 10) with type i diabetes treated with continuous subcutaneous insulin infusion (HbA(1c) 7.6% ± 1.0) were studied. The protocol consisted of two phases: acute insulin withdrawal of up to 8 h followed by a further 2-h period of insulin replacement. For the first phase the basal insulin infusion was stopped (at 0300 h), and for the second a single dose of either regular human or insulin lispro was given subcutaneously (0.2 U/kg). Plasma insulin, glucose, growth hormone, glucagon, IGF-1, free IGF-1, IGFBP-1, -2, -3 and leptin were measured. Results: After interruption of the basal insulin infusion, plasma free insulin levels fell from 60 ± 12.0 pmol/L to 10.8 ± 4.2 pmol/L, and plasma glucose rose from 5.6 ± 0.4 mmol/L to 14.8 ± 1.2 mmol/L (P < 0.01). During insulin withdrawal, IGFBP-1 increased by more than 6-fold (from 32 ± 8 to 205 ± 17 ng/mL, P < 0.001), IGFBP-3 increased significantly (from 2631 ± 118 to 3053 ± 101 ng/mL, P < 0.001), and total IGF-1 levels declined modestly (from 226 ± 33 to 182 ± 26 ng/mL, P < 0.001). In contrast, free IGF-1 concentrations (0.72 ± 0.22 ng/mL at baseline) were markedly suppressed during insulin withdrawal to values below the detection limit of the assay (0.08 ng/mL) in 15 of the 17 patients (P < 0.001). Circulating plasma leptin declined markedly in females from 20 ± 3 ng/mL to 11 ± 2 ng/mL (P < 0.0001) and in males from 10 ± 2 ng/mL to 7 ± 2 ng/mL (P < 0.02). Within 2 h of insulin replacement, the changes in circulating concentrations of IGFBP-1 and IGFBP-3 were partially reversed, and free IGF-1 levels rebounded to 0.54 ± 0.22 ng/mL (P < 0.1 vs. insulin withdrawal). Growth hormone, glucagon, and IGFBP-2 levels did not change significantly throughout the study. Despite the rapid restoration of plasma insulin and substrate levels, circulating leptin levels continued to fall in the 2-h period after insulin replacement in both females and males. The marked reduction in circulating free IGF-1 after insulin withdrawal and its increase after insulin administration suggest that acute changes in IGFBP concentrations induced by insulin are important regulators of IGF-1 bioavailability in patients with type 1 diabetes. In both males and females, the rapid induction of severe insulin deficiency is associated with a consistent fall in plasma leptin levels.

Original languageEnglish (US)
Pages (from-to)2324-2328
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number7
StatePublished - 1999
Externally publishedYes

Fingerprint

Somatomedins
Medical problems
Leptin
Type 1 Diabetes Mellitus
Insulin
Insulin-Like Growth Factor Binding Protein 1
Plasmas
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 3
Glucagon
Growth Hormone
Insulin Lispro
Subcutaneous Infusions
Glucose
Insulin-Like Growth Factor Binding Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes. / Attia, Najya; Caprio, Sonia; Jones, Timothy W.; Heptulla, Rubina; Holcombe, John; Silver, David; Sherwin, Robert S.; Tamborlane, William V.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 7, 1999, p. 2324-2328.

Research output: Contribution to journalArticle

Attia, N, Caprio, S, Jones, TW, Heptulla, R, Holcombe, J, Silver, D, Sherwin, RS & Tamborlane, WV 1999, 'Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 7, pp. 2324-2328.
Attia, Najya ; Caprio, Sonia ; Jones, Timothy W. ; Heptulla, Rubina ; Holcombe, John ; Silver, David ; Sherwin, Robert S. ; Tamborlane, William V. / Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 1999 ; Vol. 84, No. 7. pp. 2324-2328.
@article{ee38518b89d747e69a75026408567892,
title = "Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes",
abstract = "To determine the effect of acute insulin withdrawal and its subsequent replacement on components of the insulin-like growth factor (IGF)-1 binding protein system and on circulating leptin levels in patients with type 1 diabetes. Seventeen patients (age 31 yr ± 10) with type i diabetes treated with continuous subcutaneous insulin infusion (HbA(1c) 7.6{\%} ± 1.0) were studied. The protocol consisted of two phases: acute insulin withdrawal of up to 8 h followed by a further 2-h period of insulin replacement. For the first phase the basal insulin infusion was stopped (at 0300 h), and for the second a single dose of either regular human or insulin lispro was given subcutaneously (0.2 U/kg). Plasma insulin, glucose, growth hormone, glucagon, IGF-1, free IGF-1, IGFBP-1, -2, -3 and leptin were measured. Results: After interruption of the basal insulin infusion, plasma free insulin levels fell from 60 ± 12.0 pmol/L to 10.8 ± 4.2 pmol/L, and plasma glucose rose from 5.6 ± 0.4 mmol/L to 14.8 ± 1.2 mmol/L (P < 0.01). During insulin withdrawal, IGFBP-1 increased by more than 6-fold (from 32 ± 8 to 205 ± 17 ng/mL, P < 0.001), IGFBP-3 increased significantly (from 2631 ± 118 to 3053 ± 101 ng/mL, P < 0.001), and total IGF-1 levels declined modestly (from 226 ± 33 to 182 ± 26 ng/mL, P < 0.001). In contrast, free IGF-1 concentrations (0.72 ± 0.22 ng/mL at baseline) were markedly suppressed during insulin withdrawal to values below the detection limit of the assay (0.08 ng/mL) in 15 of the 17 patients (P < 0.001). Circulating plasma leptin declined markedly in females from 20 ± 3 ng/mL to 11 ± 2 ng/mL (P < 0.0001) and in males from 10 ± 2 ng/mL to 7 ± 2 ng/mL (P < 0.02). Within 2 h of insulin replacement, the changes in circulating concentrations of IGFBP-1 and IGFBP-3 were partially reversed, and free IGF-1 levels rebounded to 0.54 ± 0.22 ng/mL (P < 0.1 vs. insulin withdrawal). Growth hormone, glucagon, and IGFBP-2 levels did not change significantly throughout the study. Despite the rapid restoration of plasma insulin and substrate levels, circulating leptin levels continued to fall in the 2-h period after insulin replacement in both females and males. The marked reduction in circulating free IGF-1 after insulin withdrawal and its increase after insulin administration suggest that acute changes in IGFBP concentrations induced by insulin are important regulators of IGF-1 bioavailability in patients with type 1 diabetes. In both males and females, the rapid induction of severe insulin deficiency is associated with a consistent fall in plasma leptin levels.",
author = "Najya Attia and Sonia Caprio and Jones, {Timothy W.} and Rubina Heptulla and John Holcombe and David Silver and Sherwin, {Robert S.} and Tamborlane, {William V.}",
year = "1999",
language = "English (US)",
volume = "84",
pages = "2324--2328",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes

AU - Attia, Najya

AU - Caprio, Sonia

AU - Jones, Timothy W.

AU - Heptulla, Rubina

AU - Holcombe, John

AU - Silver, David

AU - Sherwin, Robert S.

AU - Tamborlane, William V.

PY - 1999

Y1 - 1999

N2 - To determine the effect of acute insulin withdrawal and its subsequent replacement on components of the insulin-like growth factor (IGF)-1 binding protein system and on circulating leptin levels in patients with type 1 diabetes. Seventeen patients (age 31 yr ± 10) with type i diabetes treated with continuous subcutaneous insulin infusion (HbA(1c) 7.6% ± 1.0) were studied. The protocol consisted of two phases: acute insulin withdrawal of up to 8 h followed by a further 2-h period of insulin replacement. For the first phase the basal insulin infusion was stopped (at 0300 h), and for the second a single dose of either regular human or insulin lispro was given subcutaneously (0.2 U/kg). Plasma insulin, glucose, growth hormone, glucagon, IGF-1, free IGF-1, IGFBP-1, -2, -3 and leptin were measured. Results: After interruption of the basal insulin infusion, plasma free insulin levels fell from 60 ± 12.0 pmol/L to 10.8 ± 4.2 pmol/L, and plasma glucose rose from 5.6 ± 0.4 mmol/L to 14.8 ± 1.2 mmol/L (P < 0.01). During insulin withdrawal, IGFBP-1 increased by more than 6-fold (from 32 ± 8 to 205 ± 17 ng/mL, P < 0.001), IGFBP-3 increased significantly (from 2631 ± 118 to 3053 ± 101 ng/mL, P < 0.001), and total IGF-1 levels declined modestly (from 226 ± 33 to 182 ± 26 ng/mL, P < 0.001). In contrast, free IGF-1 concentrations (0.72 ± 0.22 ng/mL at baseline) were markedly suppressed during insulin withdrawal to values below the detection limit of the assay (0.08 ng/mL) in 15 of the 17 patients (P < 0.001). Circulating plasma leptin declined markedly in females from 20 ± 3 ng/mL to 11 ± 2 ng/mL (P < 0.0001) and in males from 10 ± 2 ng/mL to 7 ± 2 ng/mL (P < 0.02). Within 2 h of insulin replacement, the changes in circulating concentrations of IGFBP-1 and IGFBP-3 were partially reversed, and free IGF-1 levels rebounded to 0.54 ± 0.22 ng/mL (P < 0.1 vs. insulin withdrawal). Growth hormone, glucagon, and IGFBP-2 levels did not change significantly throughout the study. Despite the rapid restoration of plasma insulin and substrate levels, circulating leptin levels continued to fall in the 2-h period after insulin replacement in both females and males. The marked reduction in circulating free IGF-1 after insulin withdrawal and its increase after insulin administration suggest that acute changes in IGFBP concentrations induced by insulin are important regulators of IGF-1 bioavailability in patients with type 1 diabetes. In both males and females, the rapid induction of severe insulin deficiency is associated with a consistent fall in plasma leptin levels.

AB - To determine the effect of acute insulin withdrawal and its subsequent replacement on components of the insulin-like growth factor (IGF)-1 binding protein system and on circulating leptin levels in patients with type 1 diabetes. Seventeen patients (age 31 yr ± 10) with type i diabetes treated with continuous subcutaneous insulin infusion (HbA(1c) 7.6% ± 1.0) were studied. The protocol consisted of two phases: acute insulin withdrawal of up to 8 h followed by a further 2-h period of insulin replacement. For the first phase the basal insulin infusion was stopped (at 0300 h), and for the second a single dose of either regular human or insulin lispro was given subcutaneously (0.2 U/kg). Plasma insulin, glucose, growth hormone, glucagon, IGF-1, free IGF-1, IGFBP-1, -2, -3 and leptin were measured. Results: After interruption of the basal insulin infusion, plasma free insulin levels fell from 60 ± 12.0 pmol/L to 10.8 ± 4.2 pmol/L, and plasma glucose rose from 5.6 ± 0.4 mmol/L to 14.8 ± 1.2 mmol/L (P < 0.01). During insulin withdrawal, IGFBP-1 increased by more than 6-fold (from 32 ± 8 to 205 ± 17 ng/mL, P < 0.001), IGFBP-3 increased significantly (from 2631 ± 118 to 3053 ± 101 ng/mL, P < 0.001), and total IGF-1 levels declined modestly (from 226 ± 33 to 182 ± 26 ng/mL, P < 0.001). In contrast, free IGF-1 concentrations (0.72 ± 0.22 ng/mL at baseline) were markedly suppressed during insulin withdrawal to values below the detection limit of the assay (0.08 ng/mL) in 15 of the 17 patients (P < 0.001). Circulating plasma leptin declined markedly in females from 20 ± 3 ng/mL to 11 ± 2 ng/mL (P < 0.0001) and in males from 10 ± 2 ng/mL to 7 ± 2 ng/mL (P < 0.02). Within 2 h of insulin replacement, the changes in circulating concentrations of IGFBP-1 and IGFBP-3 were partially reversed, and free IGF-1 levels rebounded to 0.54 ± 0.22 ng/mL (P < 0.1 vs. insulin withdrawal). Growth hormone, glucagon, and IGFBP-2 levels did not change significantly throughout the study. Despite the rapid restoration of plasma insulin and substrate levels, circulating leptin levels continued to fall in the 2-h period after insulin replacement in both females and males. The marked reduction in circulating free IGF-1 after insulin withdrawal and its increase after insulin administration suggest that acute changes in IGFBP concentrations induced by insulin are important regulators of IGF-1 bioavailability in patients with type 1 diabetes. In both males and females, the rapid induction of severe insulin deficiency is associated with a consistent fall in plasma leptin levels.

UR - http://www.scopus.com/inward/record.url?scp=0033306082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033306082&partnerID=8YFLogxK

M3 - Article

C2 - 10404797

AN - SCOPUS:0033306082

VL - 84

SP - 2324

EP - 2328

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -