Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates

Rachel M. Williams, Kevin Yuen, Debbie White, Beth Mallard, R. Neil Dalton, Carlo L. Acerini, David B. Dunger

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: Young adults with type 1 diabetes mellitus (T1DM) have increased glomerular filtration rate (GFR), which may mediate progressive renal disease and microalbuminuria. This may be secondary to low concentrations of insulin-like growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that restoration of circulating IGF-I concentrations in young adults with T1DM might suppress GH secretion, GFR and urinary albumin excretion. Design: In a randomized double blind crossover study six young adults with T1DM (three men, 19-24 years) received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein (IGFBP)-3 complex (SomatoKine®) 0·4 mg/kg/day and placebo. Subjects underwent overnight insulin infusion for euglycaemia, followed by determination of GFR and albumin excretion rate. Results: Following IGF-I/IGFBP-3 complex, overnight insulin requirements (0·15 vs placebo 0·21 mU/kg/min, P <0·04), plasma insulin (77 vs placebo 152 pmol/l, P <0·01) and mean overnight GH (2·6 vs placebo 4·8 mU/l, P <0·04) fell. IGF-I (492 vs placebo 218 ng/ml, P <0·01) and IGFBP-3 (4·5 vs placebo 3·9 μg/ml, P <0·05) increased. GFR did not change (145·5 (23·9) ml/min/1·73 m2 post-IGF-I/IGFBP-3 complex vs 152·2 (19·8) post placebo). Albumin excretion rate did not change 9·5 (5·5-16·6)mg/24 h pre- vs 11·5 (9·9-20·2) post-IGF-I/IGFBP-3 complex and 10·7 (8·1-21·2) pre- vs 11·5 (8·7-29·9) post placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex (mean ± SD, 56·2 ± 16·8 μmol/l) vs placebo (61·5, 45·0, P <0·02). Conclusions: Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.

Original languageEnglish (US)
Pages (from-to)439-445
Number of pages7
JournalClinical Endocrinology
Volume65
Issue number4
DOIs
StatePublished - Oct 2006
Externally publishedYes

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Somatomedins
Type 1 Diabetes Mellitus
Insulin-Like Growth Factor Binding Protein 3
Growth Hormone
Insulin-Like Growth Factor I
Young Adult
Albumins
Placebos
Glomerular Filtration Rate
Insulin
Double-Blind Method
Cross-Over Studies
Insulin Resistance
Creatinine
Kidney
Therapeutics

ASJC Scopus subject areas

  • Endocrinology

Cite this

Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates. / Williams, Rachel M.; Yuen, Kevin; White, Debbie; Mallard, Beth; Dalton, R. Neil; Acerini, Carlo L.; Dunger, David B.

In: Clinical Endocrinology, Vol. 65, No. 4, 10.2006, p. 439-445.

Research output: Contribution to journalArticle

Williams, Rachel M. ; Yuen, Kevin ; White, Debbie ; Mallard, Beth ; Dalton, R. Neil ; Acerini, Carlo L. ; Dunger, David B. / Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates. In: Clinical Endocrinology. 2006 ; Vol. 65, No. 4. pp. 439-445.
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T1 - Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates

AU - Williams, Rachel M.

AU - Yuen, Kevin

AU - White, Debbie

AU - Mallard, Beth

AU - Dalton, R. Neil

AU - Acerini, Carlo L.

AU - Dunger, David B.

PY - 2006/10

Y1 - 2006/10

N2 - Objective: Young adults with type 1 diabetes mellitus (T1DM) have increased glomerular filtration rate (GFR), which may mediate progressive renal disease and microalbuminuria. This may be secondary to low concentrations of insulin-like growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that restoration of circulating IGF-I concentrations in young adults with T1DM might suppress GH secretion, GFR and urinary albumin excretion. Design: In a randomized double blind crossover study six young adults with T1DM (three men, 19-24 years) received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein (IGFBP)-3 complex (SomatoKine®) 0·4 mg/kg/day and placebo. Subjects underwent overnight insulin infusion for euglycaemia, followed by determination of GFR and albumin excretion rate. Results: Following IGF-I/IGFBP-3 complex, overnight insulin requirements (0·15 vs placebo 0·21 mU/kg/min, P <0·04), plasma insulin (77 vs placebo 152 pmol/l, P <0·01) and mean overnight GH (2·6 vs placebo 4·8 mU/l, P <0·04) fell. IGF-I (492 vs placebo 218 ng/ml, P <0·01) and IGFBP-3 (4·5 vs placebo 3·9 μg/ml, P <0·05) increased. GFR did not change (145·5 (23·9) ml/min/1·73 m2 post-IGF-I/IGFBP-3 complex vs 152·2 (19·8) post placebo). Albumin excretion rate did not change 9·5 (5·5-16·6)mg/24 h pre- vs 11·5 (9·9-20·2) post-IGF-I/IGFBP-3 complex and 10·7 (8·1-21·2) pre- vs 11·5 (8·7-29·9) post placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex (mean ± SD, 56·2 ± 16·8 μmol/l) vs placebo (61·5, 45·0, P <0·02). Conclusions: Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.

AB - Objective: Young adults with type 1 diabetes mellitus (T1DM) have increased glomerular filtration rate (GFR), which may mediate progressive renal disease and microalbuminuria. This may be secondary to low concentrations of insulin-like growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that restoration of circulating IGF-I concentrations in young adults with T1DM might suppress GH secretion, GFR and urinary albumin excretion. Design: In a randomized double blind crossover study six young adults with T1DM (three men, 19-24 years) received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein (IGFBP)-3 complex (SomatoKine®) 0·4 mg/kg/day and placebo. Subjects underwent overnight insulin infusion for euglycaemia, followed by determination of GFR and albumin excretion rate. Results: Following IGF-I/IGFBP-3 complex, overnight insulin requirements (0·15 vs placebo 0·21 mU/kg/min, P <0·04), plasma insulin (77 vs placebo 152 pmol/l, P <0·01) and mean overnight GH (2·6 vs placebo 4·8 mU/l, P <0·04) fell. IGF-I (492 vs placebo 218 ng/ml, P <0·01) and IGFBP-3 (4·5 vs placebo 3·9 μg/ml, P <0·05) increased. GFR did not change (145·5 (23·9) ml/min/1·73 m2 post-IGF-I/IGFBP-3 complex vs 152·2 (19·8) post placebo). Albumin excretion rate did not change 9·5 (5·5-16·6)mg/24 h pre- vs 11·5 (9·9-20·2) post-IGF-I/IGFBP-3 complex and 10·7 (8·1-21·2) pre- vs 11·5 (8·7-29·9) post placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex (mean ± SD, 56·2 ± 16·8 μmol/l) vs placebo (61·5, 45·0, P <0·02). Conclusions: Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.

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