This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuen, K. Articles by Dunger, D. Search for Related Content PubMed PubMed Citation Articles by Yuen, K. Articles by Dunger, D.

The Effects of Short-Term Administration of Two Low Doses Versus the Standard GH Replacement Dose on Insulin Sensitivity and Fasting Glucose Levels in Young Healthy Adults

University Department of Pediatrics (K.Y., K.O., D.D.), Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom; Department of Endocrinology (S.H., J.W.), Radcliffe Infirmary, Oxford OX2 6HE, United Kingdom; Pharmacia \|[amp ]\| Upjohn, Inc. Ltd. (P.C., L.F.), Stockholm SE-112 87, Sweden; University of Auckland (P.G.), Auckland, New Zealand; University Children’s Hospitals (M.R.), Tubingen, Germany D-72076; and Oregon Health Science University (D.C., R.R.), Portland, Oregon 97201

Address all correspondence and requests for reprints to: Prof. David B. Dunger, University Department of Pediatrics, Level 8, Box 116, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom. E-Mail: . dbd25{at}cam.ac.uk

Abstract

GH has both diabetogenic and insulin-like actions. Supraphysiological GH doses are known to reduce insulin sensitivity (S_I), but lower doses are less well studied. We therefore compared the effects of two physiological GH doses (intermediate, 0.0033 mg/kg·d; low, 0.0017 mg/kg·d) with the standard adult GH deficiency replacement dose (standard, 0.008 mg/kg·d) on S_I, ß-cell function, IGF-I, and IGF binding proteins (IGFBPs)-1 and -3 in healthy adults.

Eleven healthy nonobese volunteers (4 males and 7 females, aged 21–38 yr) received 7 daily injections of the standard and intermediate GH doses, and 10 (5 males and 5 females, aged 21–38 yr) received the low dose. Fasting blood samples were collected daily (days 1–8). S_I and ß-cell function were calculated using the Homeostasis model assessment.

All GH doses increased IGF-I and IGFBP-3 levels, with the standard dose inducing the greatest rise (P < 0.001). At day 2 vs. baseline, all three doses increased the IGF-I/IGFBP-3 ratio, but only the standard dose lowered IGFBP-1 levels (P = 0.03). The standard dose reduced S_I (P = 0.01), whereas the intermediate dose increased S_I (P < 0.005) and lowered fasting insulin levels (P < 0.01). The low dose did not modify S_I, but reduced fasting glucose levels (P < 0.0001) and increased ß-cell function (P = 0.001). Males demonstrated higher IGF-I and IGFBP-3 responsiveness to the standard dose than females. Males also showed greater increase in S_I and decrease in fasting glucose levels on both intermediate and low doses.

In conclusion, the metabolic effects of GH are dose- and gender-dependent. The standard adult GH deficiency replacement dose induced insulin resistance, whereas lower doses improved S_I, especially in males. The low GH dose lowered fasting glucose levels and could represent the optimal dose to stimulate ß-cell function without compromising S_I in insulin-resistant GH-deficient adults.

This article has been cited by other articles:

				M. Pasarica, J. J. Zachwieja, L. DeJonge, S. Redman, and S. R. Smith Effect of Growth Hormone on Body Composition and Visceral Adiposity in Middle-Aged Men with Visceral Obesity J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4265 - 4270. [Abstract] [Full Text] [PDF]

				H. Volzke, N. Friedrich, S. Schipf, R. Haring, J. Ludemann, M. Nauck, M. Dorr, G. Brabant, and H. Wallaschofski Association between Serum Insulin-Like Growth Factor-I Levels and Thyroid Disorders in a Population-Based Study J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 4039 - 4045. [Abstract] [Full Text] [PDF]

				M.-H. Gannage-Yared, S. Khalife, M. Semaan, F. Fares, S. Jambart, and G. Halaby Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men. Eur. J. Endocrinol., July 1, 2006; 155(1): 167 - 176. [Abstract] [Full Text] [PDF]

				K. Yuen, J. Frystyk, M. Umpleby, L. Fryklund, and D. Dunger Changes in Free Rather Than Total Insulin-Like Growth Factor-I Enhance Insulin Sensitivity and Suppress Endogenous Peak Growth Hormone (GH) Release following Short-Term Low-Dose GH Administration in Young Healthy Adults J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3956 - 3964. [Abstract] [Full Text] [PDF]

				S. M. Harman and M. R. Blackman Hormones and Supplements: Do They Work?: Use of Growth Hormone for Prevention or Treatment of Effects of Aging J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2004; 59(7): B652 - B658. [Abstract] [Full Text] [PDF]