Advertisement

Endocrine

, Volume 59, Issue 3, pp 643–650 | Cite as

Glucose homeostasis in GHD children during long-term replacement therapy: a case−control study

  • Donatella Capalbo
  • Andrea Esposito
  • Nicola Improda
  • Malgorzata Gabriela Wasniewska
  • Raffaella Di Mase
  • Filippo De Luca
  • Dario Bruzzese
  • Mariacarolina SalernoEmail author
Original Article

Abstract

Purpose

To evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy.

Methods

We evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years.

Results

No difference was detected at baseline between GHD patients and controls in glucose (79.58 ± 9.96 vs. 77.18 ± 8.20 mg/dl), insulin (4.50 ± 3.24 vs. 4.30 ± 2.60 µU/ml), HbA1c (5.20 ± 0.31 vs. 5.25 ± 0.33%) levels, and HOMA-IR (0.93 ± 0.72 vs. 0.86 ± 0.61). One year of GH was associated with a significant increase in insulin (7.21 ± 4.84, p < 0.001) and HOMA-IR (1.32 ± 0.98, p < 0.001) in GHD children, which became different from controls (p < 0.001 and p = 0.004). These parameters did not change further during the following years of treatment in GHD subjects. In contrast, controls did not show significant changes in insulin (4.40 ± 2.60) and HOMA-IR (0.82 ± 0.60) during the first year; however, at the fifth year of the study a significant increase in insulin (6.50 ± 3.50, p = 0.004) and HOMA-IR (1.29 ± 0.54, p < 0.001) was documented, making these parameters comparable between patients and controls.

Conclusions

Our results suggest that growth hormone (GH) treatment is not associated with significant impairment of insulin sensitivity in GHD children. The slight impairment observed in GHD adolescents after long-term GH is comparable to that physiologically occurring in healthy pubertal subjects.

Keywords

Growth hormone deficiency GH replacement therapy Glucose homeostasis Insulin sensitivity 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration.

Informed consent

Informed parental consent for participation in the study was obtained for patients and controls and the study was authorized by the Hospital Ethical Research Committee.

References

  1. 1.
    N. Møller, J.O. Jørgensen, Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr. Rev. 30, 152–177 (2009)CrossRefGoogle Scholar
  2. 2.
    M. Salerno, V. Esposito, V. Farina, G. Radetti, A. Umbaldo, D. Capalbo, L. Spinelli, S. Muzzica, G. Lombardi, A. Colao, Improvement of cardiac performance and cardiovascular risk factors in children with GH deficiency after two years of GH replacement therapy: an observational, open, prospective, case-control study. J. Clin. Endocrinol. Metab. 91, 1288–1295 (2006)CrossRefGoogle Scholar
  3. 3.
    D. Capalbo, A. Lo Vecchio, V. Farina, L. Spinelli, A. Palladino, C. Tiano, T. Lettiero, G. Lombardi, A. Colao, M. Salerno, Subtle alterations of cardiac performance in children with growth hormone deficiency: results of a two-year prospective, case-control study. J. Clin. Endocrinol. Metab. 94, 3347–3355 (2009)CrossRefGoogle Scholar
  4. 4.
    D. Capalbo, G. Mattace Raso, A. Esposito, R. Di Mase, F. Barbieri, R. Meli, D. Bruzzese, M. Salerno, Cluster of cardiometabolic risk factors in children with GH deficiency: a prospective, case-control study. Clin. Endocrinol. 80, 856–862 (2014)CrossRefGoogle Scholar
  5. 5.
    J. Rothermel, T. Reinehr, Metabolic alterations in paediatric GH deficiency. Best Pract. Res. Clin. Endocrinol. Metab. 30, 757–770 (2016)CrossRefGoogle Scholar
  6. 6.
    A. Luger, A.F. Mattsson, M. Koltowska-Häggström, M. Thunander, M. Góth, J. Verhelst, R. Abs, Incidence of diabetes mellitus and evolution of glucose parameters in growth hormone-deficient subjects during growth hormone replacement therapy: a long-term observational study. Diabetes Care 35, 57–62 (2012)CrossRefGoogle Scholar
  7. 7.
    M. Segerlantz, M. Bramnert, P. Manhem, E. Laurila, L.C. Groop, Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults. Eur. J. Endocrinol. 149, 511–519 (2003)CrossRefGoogle Scholar
  8. 8.
    F.P. Dominici, D. Turyn, Growth hormone-induced alterations in the insulin-signaling system. Exp. Biol. Med. 227, 149–157 (2002)CrossRefGoogle Scholar
  9. 9.
    K.C. Yuen, D.B. Dunger, Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adults. Diabetes Obes. Metab. 9, 11–22 (2007)CrossRefGoogle Scholar
  10. 10.
    A. Ciresi, M.C. Amato, A. Criscimanna, A. Mattina, C. Vetro, A. Galluzzo, G. D’Acquisto, C. Giordano, Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency. Eur. J. Endocrinol. 156, 353–360 (2007)CrossRefGoogle Scholar
  11. 11.
    J.P. López-Siguero, L.F. López-Canti, R. Espino, E. Caro, J.M. Fernández-García, A. Gutiérrez-Macías, J.M. Rial, J.L. Lechuga, F. Macías, M.J. Martínez-Aedo, S. Rico, I. Rodríguez, J. Guillén, F.J. Arroyo, S. Bernal, R. Espigares, M. Núñez, A. Escribano, J.L. Barrionuevo, J. Gentil, V. Barrios, A. Fernández-Nistal, G.A. Martos-Moreno, V. Martínez, J. Argente, Effect of recombinant growth hormone on leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α and ghrelin levels in growth hormone-deficient children. J. Endocrinol. Invest. 34, 300–306 (2011)CrossRefGoogle Scholar
  12. 12.
    A. Ciresi, M.C. Amato, C. Giordano, Reduction in insulin sensitivity and inadequate β-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment. J. Endocrinol. Invest. 38, 351–359 (2015)CrossRefGoogle Scholar
  13. 13.
    A. Ciresi, F. Cicciò, S. Radellini, C. Giordano, Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency. Growth Horm. IGF Res. 29, 71–77 (2016)CrossRefGoogle Scholar
  14. 14.
    F. Baronio, L. Mazzanti, Y. Girtler, F. Tamburrino, A. Fazzi, F. Lupi, S. Longhi, G. Radetti, The influence of growth hormone treatment on glucose homeostasis in growth hormone-deficient children: a six-year follow-up study. Horm. Res. Paediatr. 86, 196–200 (2016)CrossRefGoogle Scholar
  15. 15.
    G. Radetti, B. Pasquino, E. Gottardi, I.B. Contadin, F. Rigon, G. Aimaretti, Insulin sensitivity in growth hormone-deficient children: influence of replacement treatment. Clin. Endocrinol. 61, 473–477 (2004)CrossRefGoogle Scholar
  16. 16.
    W.S. Cutfield, P. Wilton, H. Bennmarker, K. Albertsson-Wikland, P. Chatelain, M.B. Ranke, D.A. Price, Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 355, 610–613 (2000)CrossRefGoogle Scholar
  17. 17.
    C.J. Child, A.G. Zimmermann, R.S. Scott, G.B. Cutler Jr, T. Battelino, W.F. Blum, GeNeSIS international advisory board: prevalence and incidence of diabetes mellitus in GH-treated children and adolescents: analysis from the GeNeSIS observational research program. J. Clin. Endocrinol. Metab. 96, E1025–E1034 (2011)CrossRefGoogle Scholar
  18. 18.
    A. Poidvin, A. Weill, E. Ecosse, J. Coste, J.C. Carel, Risk of diabetes treated in early adulthood following growth hormone treatment for short stature in childhood. J. Clin. Endocrinol. Metab. 102, 1291–1298 (2017)CrossRefGoogle Scholar
  19. 19.
    Growth Hormone Research Society, Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J. Clin. Endocrinol. Metab. 85, 3990–3993 (2000)Google Scholar
  20. 20.
    D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985)CrossRefGoogle Scholar
  21. 21.
    E. Cacciari, S. Milani, A. Balsamo, E. Spada, G. Bona, L. Cavallo, F. Cerutti, L. Gargantini, N. Greggio, G. Tonini, A. Cicognani, Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J. Endocrinol. Invest. 29, 581–593 (2006)CrossRefGoogle Scholar
  22. 22.
    W.T. Friedewald, R.I. Levy, D.S. Fredrickson, Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502 (1972)PubMedGoogle Scholar
  23. 23.
    W.P. Castelli, Lipids, risk factors and ischaemic heart disease. Atherosclerosis 124, S1–S9 (1996)CrossRefGoogle Scholar
  24. 24.
    M.I. Goran, B.A. Gower, Longitudinal study on pubertal insulin resistance. Diabetes 50, 2444–2450 (2001)CrossRefGoogle Scholar
  25. 25.
    T.S. Hannon, J. Janosky, S.A. Arslanian, Longitudinal study of physiologic insulin resistance and metabolic changes of puberty. Pediatr. Res. 60, 759–763 (2006)CrossRefGoogle Scholar
  26. 26.
    B. Singh, A. Saxena, Surrogate markers of insulin resistance: A review. World J. Diabetes 1, 36–47 (2010)CrossRefGoogle Scholar
  27. 27.
    M. Matsuda, R.A. DeFronzo, Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462–1470 (1999)CrossRefGoogle Scholar
  28. 28.
    E. Bonora, G. Targher, M. Alberiche, R.C. Bonadonna, F. Saggiani, M.B. Zenere, T. Monauni, M. Muggeo, Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23, 57–63 (2000)CrossRefGoogle Scholar
  29. 29.
    R. Muniyappa, S. Lee, H. Chen, M.J. Quon, Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am. J. Physiol. Endocrinol. Metab. 294, E15–E26 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Donatella Capalbo
    • 1
  • Andrea Esposito
    • 2
  • Nicola Improda
    • 1
  • Malgorzata Gabriela Wasniewska
    • 3
  • Raffaella Di Mase
    • 1
  • Filippo De Luca
    • 3
  • Dario Bruzzese
    • 4
  • Mariacarolina Salerno
    • 2
    Email author
  1. 1.Department of PediatricsUniversity “Federico II” of NaplesNaplesItaly
  2. 2.Department of Translational Medical Sciences Pediatric Endocrinology SectionUniversity “Federico II” of NaplesNaplesItaly
  3. 3.Department of Pediatric Gynecological, Microbiological and Biomedical SciencesUniversity of MessinaMessinaItaly
  4. 4.Department of Public HealthUniversity “Federico II” of NaplesNaplesItaly

Personalised recommendations