Journal of Clinical Endocrinology & Metabolism, Vol 69, 239-245, Copyright © 1989 by Endocrine Society

ARTICLES

Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus

CM Asplin, AC Faria, EC Carlsen, VA Vaccaro, RE Barr, A Iranmanesh, MM Lee, JD Veldhuis and WS Evans
Department of Internal Medicine, Health Sciences Center, Charlottesville, Virginia.

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin- dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				J. D. Veldhuis, L. Farhy, A. L. Weltman, J. Kuipers, J. Weltman, and L. Wideman Gender Modulates Sequential Suppression and Recovery of Pulsatile Growth Hormone Secretion by Physiological Feedback Signals in Young Adults J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2874 - 2881. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. T. Patrie, K. T. Brill, J. Y. Weltman, E. E. Mueller, C. Y. Bowers, and A. Weltman Contributions of Gender and Systemic Estradiol and Testosterone Concentrations to Maximal Secretagogue Drive of Burst-Like Growth Hormone Secretion in Healthy Middle-Aged and Older Adults J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6291 - 6296. [Abstract] [Full Text] [PDF]

				K. M. Tullis, C. J. Krebs, J. Y. M. Leung, and D. M. Robins The Regulator of Sex-Limitation Gene, Rsl, Enforces Male-Specific Liver Gene Expression by Negative Regulation Endocrinology, May 1, 2003; 144(5): 1854 - 1860. [Abstract] [Full Text] [PDF]

				P. F. Catalina, M. A. Andrade, R. V. Garcia-Mayor, and F. Mallo Altered GH Elimination Kinetics in Type 1 Diabetes Mellitus Can Explain the Elevation in Circulating Levels: Bicompartmental Approach J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1785 - 1790. [Abstract] [Full Text] [PDF]

				J. A. Gusenoff, S. M. Harman, J. D. Veldhuis, J. J. Jayme, C. St. Clair, T. Munzer, C. Christmas, K. G. O'Connor, T. E. Stevens, M. F. Bellantoni, et al. Cortisol and GH secretory dynamics, and their interrelationships, in healthy aged women and men Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E616 - E625. [Abstract] [Full Text] [PDF]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]

				S. Jain, D. W. Golde, R. Bailey, and M. E. Geffner Insulin-Like Growth Factor-I Resistance Endocr. Rev., October 1, 1998; 19(5): 625 - 646. [Abstract] [Full Text]

				P. F. Catalina, F. Mallo, M. A. Andrade, R. V. García-Mayor, and C. Diéguez Growth Hormone (GH) Response to GH-Releasing Peptide-6 in Type 1 Diabetic Patients with Exaggerated GH-Releasing Hormone-Stimulated GH Secretion J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3663 - 3667. [Abstract] [Full Text]

				M. Scacchi, A. I. Pincelli, A. Caumo, P. Tomasi, G. Delitala, G. Baldi, and F. Cavagnini Spontaneous Nocturnal Growth Hormone Secretion in Anorexia Nervosa J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3225 - 3229. [Abstract] [Full Text] [PDF]

				K. Thrailkill, T. Quattrin, L. Baker, J. Litton, K. Dwigun, M. Rearson, M. Poppenheimer, D. Kotlovker, D. Giltinan, N. Gesundheit, et al. Dual Hormonal Replacement Therapy with Insulin and Recombinant Human Insulin-Like Growth Factor (IGF)-I in Insulin-Dependent Diabetes Mellitus: Effects on the Growth Hormone/IGF/IGF-Binding Protein System J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1181 - 1187. [Abstract] [Full Text] [PDF]

				D. J. Waxman, P. A. Ram, S.-H. Park, and H. K. Choi Intermittent Plasma Growth Hormone Triggers Tyrosine Phosphorylation and Nuclear Translocation of a Liver-Expressed, Stat 5-related DNA Binding Protein J. Biol. Chem., June 2, 1995; 270(22): 13262 - 13270. [Abstract] [Full Text] [PDF]