Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency

Kevin C J Yuen, Charles Roberts, Jan Frystyk, William Rooney, James R. Pollaro, Bethany Klopfenstein, Jonathan Purnell

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopicfat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.

Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study.

Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.

Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.

Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood sampleswere collected at baseline, and months 1 and 3, where as hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.

Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11 β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.

Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P

Original languageEnglish (US)
Pages (from-to)E1862-E1869
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

Insulin-Like Growth Factor I
Metabolism
Glucose Clamp Technique
Insulin Resistance
Hydrocortisone
Fats
Insulin
Clamping devices
Insulin-Like Growth Factor Binding Protein 3
Adipocytes
Fasting
Glucose
Placebos
11-beta-Hydroxysteroid Dehydrogenases
Insulin-Like Growth Factor Binding Protein 2
Abdominal Fat
IGF Type 1 Receptor
Insulin-Like Growth Factor II
C-Peptide
Lipolysis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

@article{537efd0b8272489d88c73fc6f32e0c29,
title = "Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency",
abstract = "Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopicfat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study.Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood sampleswere collected at baseline, and months 1 and 3, where as hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11 β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P",
author = "Yuen, {Kevin C J} and Charles Roberts and Jan Frystyk and William Rooney and Pollaro, {James R.} and Bethany Klopfenstein and Jonathan Purnell",
year = "2014",
month = "10",
day = "1",
doi = "10.1210/jc.2014-1532",
language = "English (US)",
volume = "99",
pages = "E1862--E1869",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "10",

}

TY - JOUR

T1 - Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency

AU - Yuen, Kevin C J

AU - Roberts, Charles

AU - Frystyk, Jan

AU - Rooney, William

AU - Pollaro, James R.

AU - Klopfenstein, Bethany

AU - Purnell, Jonathan

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopicfat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study.Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood sampleswere collected at baseline, and months 1 and 3, where as hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11 β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P

AB - Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopicfat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study.Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood sampleswere collected at baseline, and months 1 and 3, where as hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11 β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P

UR - http://www.scopus.com/inward/record.url?scp=84907660082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907660082&partnerID=8YFLogxK

U2 - 10.1210/jc.2014-1532

DO - 10.1210/jc.2014-1532

M3 - Article

VL - 99

SP - E1862-E1869

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -