Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

Kevin C J Yuen, Jan Frystyk, Deborah K. White, Th B. Twickler, Hans P F Koppeschaar, Philip E. Harris, Linda Fryklund, Peter R. Murgatroyd, David B. Dunger

Research output: Contribution to journalArticle

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Abstract

Objective: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin] in adults with severe GH deficiency. Patients and methods: In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 048 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. Results: The LGH decreased fasting glucose levels (P <0.01) and enhanced insulin sensitivity (P <0.02), but body composition, non-esterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P <0.05), CRP (P <0.05) and IL-6 (P <0.05) levels, and increased NEFA levels (P <0.05). No changes were observed with the untreated controls. Conclusion: Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalClinical Endocrinology
Volume63
Issue number4
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Body Composition
Growth Hormone
Insulin Resistance
C-Reactive Protein
Interleukin-6
Fasting
Fatty Acids
Glucose Clamp Technique
Lipolysis
Adiponectin
Photon Absorptiometry
Insulin-Like Growth Factor I
Type 2 Diabetes Mellitus
Young Adult
Body Mass Index
Tumor Necrosis Factor-alpha
Fats
Prospective Studies
Lipids
Glucose

ASJC Scopus subject areas

  • Endocrinology

Cite this

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. / Yuen, Kevin C J; Frystyk, Jan; White, Deborah K.; Twickler, Th B.; Koppeschaar, Hans P F; Harris, Philip E.; Fryklund, Linda; Murgatroyd, Peter R.; Dunger, David B.

In: Clinical Endocrinology, Vol. 63, No. 4, 10.2005, p. 428-436.

Research output: Contribution to journalArticle

Yuen, Kevin C J ; Frystyk, Jan ; White, Deborah K. ; Twickler, Th B. ; Koppeschaar, Hans P F ; Harris, Philip E. ; Fryklund, Linda ; Murgatroyd, Peter R. ; Dunger, David B. / Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. In: Clinical Endocrinology. 2005 ; Vol. 63, No. 4. pp. 428-436.
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T1 - Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

AU - Yuen, Kevin C J

AU - Frystyk, Jan

AU - White, Deborah K.

AU - Twickler, Th B.

AU - Koppeschaar, Hans P F

AU - Harris, Philip E.

AU - Fryklund, Linda

AU - Murgatroyd, Peter R.

AU - Dunger, David B.

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N2 - Objective: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin] in adults with severe GH deficiency. Patients and methods: In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 048 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. Results: The LGH decreased fasting glucose levels (P <0.01) and enhanced insulin sensitivity (P <0.02), but body composition, non-esterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P <0.05), CRP (P <0.05) and IL-6 (P <0.05) levels, and increased NEFA levels (P <0.05). No changes were observed with the untreated controls. Conclusion: Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.

AB - Objective: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin] in adults with severe GH deficiency. Patients and methods: In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 048 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. Results: The LGH decreased fasting glucose levels (P <0.01) and enhanced insulin sensitivity (P <0.02), but body composition, non-esterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P <0.05), CRP (P <0.05) and IL-6 (P <0.05) levels, and increased NEFA levels (P <0.05). No changes were observed with the untreated controls. Conclusion: Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.

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