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Diabetes in Patients With Acromegaly

  • Other Forms of Diabetes and Its Complications (JJ Nolan, Section Editor)
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Abstract

Purpose of Review

Acromegaly is a clinical syndrome which results from growth hormone excess. Uncontrolled acromegaly is associated with cardiovascular mortality, due to an excess of risk factors including diabetes mellitus, hypertension and cardiomegaly. Diabetes mellitus is a frequent complication of acromegaly with a prevalence of 12–37%. This review will provide an overview of a number of aspects of diabetes mellitus and glucose intolerance in acromegaly including the following:

  1. 1.

    Epidemiology and pathophysiology of abnormalities of glucose homeostasis

  2. 2.

    The impact of different management options for acromegaly on glucose homeostasis

  3. 3.

    The management options for diabetes mellitus in patients with acromegaly

Recent Findings

Growth hormone and IGF-1 have complex effects on glucose metabolism. Insulin resistance, hyperinsulinaemia and increased gluconeogenesis combine to produce a metabolic milieu which leads to the development of diabetes in acromegaly. Treatment of acromegaly should ameliorate abnormalities of glucose metabolism, due to reversal of insulin resistance and a reduction in gluconeogenesis. Recent advances in medical therapy of acromegaly have varying impacts on glucose homeostasis. These adverse effects influence management choices in patients with acromegaly who also have diabetes mellitus or glucose intolerance.

Summary

The underlying mechanisms of disorders of glucose metabolism in patients with acromegaly are complex. The aim of treatment of acromegaly is normalisation of GH/IGF-1 with reduction of co-morbidities. The choice of therapy for acromegaly should consider the impact of therapy on several factors including glucose metabolism.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301–42.

    Article  PubMed  Google Scholar 

  2. Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary. 2014;17(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  3. Moller N, Schmitz O, Joorgensen JO, Astrup J, Bak JF, Christensen SE, et al. Basal- and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy. J Clin Endocrinol Metab. 1992;74(5):1012–9.

    CAS  PubMed  Google Scholar 

  4. Ronchi C, Epaminonda P, Cappiello V, Beck-Peccoz P, Arosio M. Effects of two different somatostatin analogs on glucose tolerance in acromegaly. J Endocrinol Investig. 2002;25(6):502–7.

    Article  CAS  Google Scholar 

  5. Thankamony A, Tossavainen PH, Sleigh A, Acerini C, Elleri D, Dalton RN, et al. Short-term administration of pegvisomant improves hepatic insulin sensitivity and reduces soleus muscle intramyocellular lipid content in young adults with type 1 diabetes. J Clin Endocrinol Metab. 2014;99(2):639–47.

    Article  CAS  PubMed  Google Scholar 

  6. Dal J, Feldt-Rasmussen U, Andersen M, Kristensen LO, Laurberg P, Pedersen L, et al. Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. Eur J Endocrinol. 2016;175(3):181–90.

    Article  PubMed  Google Scholar 

  7. Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L, et al. Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol. 2012;167(2):189–98.

    CAS  PubMed  Google Scholar 

  8. Fieffe S, Morange I, Petrossians P, Chanson P, Rohmer V, Cortet C, et al. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol. 2011;164(6):877–84.

    Article  CAS  PubMed  Google Scholar 

  9. Dreval AV, Trigolosova IV, Misnikova IV, Kovalyova YA, Tishenina RS, Barsukov IA, et al. Prevalence of diabetes mellitus in patients with acromegaly. Endocr Connections. 2014;3(2):93–8.

    Article  CAS  Google Scholar 

  10. Siegel S, Streetz-van der Werf C, Schott JS, Nolte K, Karges W, Kreitschmann-Andermahr I. Diagnostic delay is associated with psychosocial impairment in acromegaly. Pituitary. 2013;16(4):507–14.

    Article  PubMed  Google Scholar 

  11. Suda K, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, et al. The prevalence of acromegaly in hospitalized patients with type 2 diabetes. Endocr J. 2015;62(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  12. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19(6):717–97.

    CAS  PubMed  Google Scholar 

  13. Vottero A, Guzzetti C, Loche S. New aspects of the physiology of the GH-IGF-1 axis. Endocr Dev. 2013;24:96–105.

    CAS  PubMed  Google Scholar 

  14. Boni-Schnetzler M, Schmid C, Meier PJ, Froesch ER. Insulin regulates insulin-like growth factor I mRNA in rat hepatocytes. Am J Phys. 1991;260(6 Pt 1):E846–51.

    CAS  Google Scholar 

  15. Moller N, Jorgensen JO, Schmitz O, Moller J, Christiansen J, Alberti KG, et al. Effects of a growth hormone pulse on total and forearm substrate fluxes in humans. Am J Phys. 1990;258(1 Pt 1):E86–91.

    CAS  Google Scholar 

  16. •• Moller N, Jorgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009;30(2):152–77. Excellent overview of metabolic effects of GH.

    Article  PubMed  Google Scholar 

  17. Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, et al. Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol. 2000;52(5):549–55.

    Article  CAS  Google Scholar 

  18. Karlander S, Vranic M, Efendic S. Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance. Diabetologia. 1986;29(11):778–83.

    Article  CAS  PubMed  Google Scholar 

  19. Elkeles RS, Wright AD, Lowy C, Fraser TR. Serum-insulin in acromegaly. Lancet. 1969;2(7621):615–8.

    Article  CAS  PubMed  Google Scholar 

  20. del Rincon JP, Iida K, Gaylinn BD, McCurdy CE, Leitner JW, Barbour LA, et al. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes. 2007;56(6):1638–46.

    Article  PubMed  Google Scholar 

  21. Pratipanawatr T, Pratipanawatr W, Rosen C, Berria R, Bajaj M, Cusi K, et al. Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects. Am J Physiol Endocrinol Metab. 2002;282(6):E1360–8.

    Article  CAS  PubMed  Google Scholar 

  22. Niculescu D, Purice M, Coculescu M. Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly. Pituitary. 2013;16(2):168–74.

    Article  CAS  PubMed  Google Scholar 

  23. Reid TJ, Jin Z, Shen W, Reyes-Vidal CM, Fernandez JC, Bruce JN, et al. IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition. Pituitary. 2015;18(6):808–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. • Alexopoulou O, Bex M, Abs R, T’Sjoen G, Velkeniers B, Maiter D. Divergence between growth hormone and insulin-like growth factor-1 concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab. 2008;93(4):1324–30. A significant proportion of patients have divergent results at follow up—clinical significance of this remains unclear.

    Article  CAS  PubMed  Google Scholar 

  25. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89(2):667–74.

    Article  CAS  PubMed  Google Scholar 

  26. Hopkins KD, Holdaway IM. Insulin secretion and insulin-like growth factor-I levels in active and controlled acromegaly. Clin Endocrinol. 1992;36(1):53–7.

    Article  CAS  Google Scholar 

  27. Baris D, Gridley G, Ron E, Weiderpass E, Mellemkjaer L, Ekbom A, et al. Acromegaly and cancer risk: a cohort study in Sweden and Denmark. Cancer Causes Control. 2002;13(5):395–400.

    Article  CAS  PubMed  Google Scholar 

  28. Cheng S, Gomez K, Serri O, Chik C, Ezzat S. The role of diabetes in acromegaly associated neoplasia. PLoS One. 2015;10(5):e0127276.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wen-Ko C, Szu-Tah C, Feng-Hsuan L, Chen-Nen C, Ming-Hsu W, Jen-Der L. The impact of diabetes mellitus on the survival of patients with acromegaly. Endokrynol Pol. 2016;67(5):501-6.

  30. Katznelson L, Laws Jr ER, Melmed S, Molitch ME, Murad MH, Utz A, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–51.

    Article  CAS  PubMed  Google Scholar 

  31. Kinoshita Y, Fujii H, Takeshita A, Taguchi M, Miyakawa M, Oyama K, et al. Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic {beta}-cell function is preserved. Eur J Endocrinol. 2011;164(4):467–73.

    Article  CAS  PubMed  Google Scholar 

  32. Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prevost G, et al. Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab. 2014;99(4):1282–90.

    Article  CAS  PubMed  Google Scholar 

  33. • Mazziotti G, Floriani I, Bonadonna S, Torri V, Chanson P, Giustina A. Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J Clin Endocrinol Metab. 2009;94(5):1500–8. Overview of the studies that assessed glucose meatbolism in SSAs.

    Article  CAS  PubMed  Google Scholar 

  34. Schmid HA, Schoeffter P. Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors. Neuroendocrinology. 2004;80 Suppl 1:47–50.

    Article  CAS  PubMed  Google Scholar 

  35. Gadelha MR, Bronstein MD, Brue T, Coculescu M, Fleseriu M, Guitelman M, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875–84.

    Article  CAS  PubMed  Google Scholar 

  36. Schmid HA, Brue T, Colao A, Gadelha MR, Shimon I, Kapur K, et al. Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine. 2016;53(1):210–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zambre Y, Ling Z, Chen MC, Hou X, Woon CW, Culler M, et al. Inhibition of human pancreatic islet insulin release by receptor-selective somatostatin analogs directed to somatostatin receptor subtype 5. Biochem Pharmacol. 1999;57(10):1159–64.

    Article  CAS  PubMed  Google Scholar 

  38. Singh V, Brendel MD, Zacharias S, Mergler S, Jahr H, Wiedenmann B, et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab. 2007;92(2):673–80.

    Article  CAS  PubMed  Google Scholar 

  39. Breitschaft A, Hu K, Hermosillo Resendiz K, Darstein C, Golor G. Management of hyperglycemia associated with pasireotide (SOM230): healthy volunteer study. Diabetes Res Clin Pract. 2014;103(3):458–65.

    Article  CAS  PubMed  Google Scholar 

  40. American Diabetes Association. Standards of medical care in diabetes 2016 [updated 2016; cited 2016 october 22nd]. Available from: http://care.diabetesjournals.org/content/39/Supplement_1.

  41. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000;342(16):1171–7.

    Article  CAS  PubMed  Google Scholar 

  42. Urbani C, Sardella C, Calevro A, Rossi G, Scattina I, Lombardi M, et al. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol. 2013;169(1):99–108.

    Article  CAS  PubMed  Google Scholar 

  43. Higham CE, Rowles S, Russell-Jones D, Umpleby AM, Trainer PJ. Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab. 2009;94(7):2459–63.

    Article  CAS  PubMed  Google Scholar 

  44. Droste M, Domberg J, Buchfelder M, Mann K, Schwanke A, Stalla G, et al. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol. 2014;171(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  45. Sherlock M, Fernandez-Rodriguez E, Alonso AA, Reulen RC, Ayuk J, Clayton RN, et al. Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab. 2009;94(4):1255–63.

    Article  CAS  PubMed  Google Scholar 

  46. Rau H, Althoff PH, Schmidt K, Badenhoop K, Usadel KH. Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion. Clin Investig. 1993;71(5):372–8.

    Article  CAS  PubMed  Google Scholar 

  47. Pijl H, Ohashi S, Matsuda M, Miyazaki Y, Mahankali A, Kumar V, et al. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000;23(8):1154–61.

    Article  CAS  PubMed  Google Scholar 

  48. Krzyzanowska K, Schnack C, Mittermayer F, Kopp HP, Hofer M, Kann T, et al. High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism. Exp Clin Endocrinol Diabetes. 2005;113(8):430–4.

    Article  CAS  PubMed  Google Scholar 

  49. Al-Shoumer KA, Beshyah SA, Niththyananthan R, Johnston DG. Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults. Clin Endocrinol. 1995;42(1):85–90.

    Article  CAS  Google Scholar 

  50. Gazzaruso C, Gola M, Karamouzis I, Giubbini R, Giustina A. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH—an update. J Clin Endocrinol Metab. 2014;99(1):18–29.

    Article  CAS  PubMed  Google Scholar 

  51. Lin E, Wexler TL, Nachtigall L, Tritos N, Swearingen B, Hemphill L, et al. Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly. Clin Endocrinol. 2012;77(3):430–8.

    Article  CAS  Google Scholar 

  52. Giavoli C, Profka E, Verrua E, Ronchi CL, Ferrante E, Bergamaschi S, et al. GH replacement improves quality of life and metabolic parameters in cured acromegalic patients with growth hormone deficiency. J Clin Endocrinol Metab. 2012;97(11):3983–8.

    Article  CAS  PubMed  Google Scholar 

  53. Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013;16(3):294–302.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to M. Sherlock.

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Conflict of Interest

A.M. Hannon reports grants from Pfizer and Royal College of Surgeons Ireland.

C.J. Thompson reports grants from Pfizer.

M. Sherlock has received research funding from Pfizer and Novartis.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications

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Hannon, A.M., Thompson, C.J. & Sherlock, M. Diabetes in Patients With Acromegaly. Curr Diab Rep 17, 8 (2017). https://doi.org/10.1007/s11892-017-0838-7

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