DIABETES MELLITUS IN NEUROENDOCRINE DISEASES

Cover Page


Cite item

Full Text

Abstract

There are many endocrine diseases accompanied by development of secondary diabetes mellitus (sDM). The features of the development and course of sDM in acromegaly, Cushing’s syndrome, and growth hormone (GH) deficiency are of particular interest as the prevalence of sDM associated with these pathologies is higher than that in the population. The main risk factors for sDM in acromegaly are age, female gender, arterial hypertension, family history of type 2 DM (T2DM), acromegaly activity, and duration and certain treatment methods of acromegaly. The differences of the sDM pathogenesis from pathogenesis of T2DM in the population are due to the opposite effect of GH and insulin-like growth factor 1 on glucose metabolism as well as to effect of acromegaly treatment on the mechanisms of diabetes development. The prevalence of diabetes in patients with GH deficiency, especially against the background of GH replacement therapy, is slightly higher than that in population. However, some studies have shown that GH replacement therapy may lead to normalization of the impaired glucose metabolism. High prevalence of metabolic syndrome (43%) and visceral obesity in the GH deficiency are the causes of the development of lipotoxicity (free fatty acids excess) and insulin resistance.In Cushing’s syndrome, the prevalence of early carbohydrate metabolism disturbances may reach 70%. In Cushing’s disease, chronic glucocorticoid excess determines insulin resistance and reduces insulin secretion, which results in hyperglycaemia. Currently, the recommendations for the treatment of sDM in acromegaly, hypercortisolism, and GH deficiency are the same as for the treatment of T2DM. However, as the pathogenesis is different in sDM and T2DM, the new algorithms for the diagnosis, prevention and treatment need to be developed. Prevention and timely treatment based on pathological principals will slow down the development of micro- and macrovascular complications leading to early disability and death of patients with neuroendocrine diseases.

About the authors

I. V. Trigolosova

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Author for correspondence.
Email: trigolosova_ira@mail.ru
PhD, senior scientific worker, Department of Therapeutic Endocrinology, MONIKI Россия

A. V. Vinogradova

Moscow Regional Research and Clinical Institute (MONIKI); 61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Email: fake@neicon.ru
MD, physician-endocrinologist, Department of Therapeutic Endocrinology, MONIKI Россия

M. V. Kruglyakova

Municipal Hospital No.3 of the Moscow Department of the Ministry of Public Health; 2/1 Kashtanovaya alleya, Zelenograd, 124489, Russian Federation

Email: fake@neicon.ru

MD, physician-endocrinologist, Consulting-and-Diagnostic Department, Municipal Hospital No.3, Zelenograd

Россия

References

  1. International Diabetes Federation. IDF Diabetes Atlas. 6th ed. International Diabetes Federation; 2013.
  2. Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999;2(1):29-41.
  3. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102-52.
  4. Древаль АВ, Триголосова ИВ, Виноградова АВ, Тишенина РС, Мисникова ИВ, Губкина ВА, Ковалева ЮА, Барсуков ИА. Распространенность ранних нарушений углеводного обмена среди больных акромегалией. Проблемы эндокринологии. 2012;(6):3-7. (Dreval’ AV, Trigolosova IV, Vinogradova AV, Tishenina RS, Misnikova IV, Gubkina VA, Kovaleva JuA, Barsukov IA. [The prevalence of early disturbances of carbohydrate metabolism among acromegaly patients]. Problemy endokrinologii. 2012;(6):3-7. Russian).
  5. Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res. 2001; 34(11):1429-33.
  6. Stelmachowska-Banaś M, Zdunowski P, Zgliczyński W. Abnormalities in glucose homeostasis in acromegaly. Does the prevalence of glucose intolerance depend on the level of activity of the disease and the duration of the symptoms? Endokrynol Pol. 2009;60(1):20-4.
  7. Biering H, Knappe G, Gerl H, Lochs H. Prevalence of diabetes in acromegaly and Cushing syndrome. Acta Med Austriaca. 2000;27(1):27-31.
  8. Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N. Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf). 2000;52(5):549-55.
  9. Gierach M, Gierach J, Pujanek M, Skowrońska A, Rutkowska E, Junik R. Aberrations in carbohydrate metabolism in patients with diagnosed acromegaly, hospitalized in the Endocrinology and Diabetology Department of Collegium Medicum University of Nicolaus Copernicus in Bydgoszcz in the years 2001-2009. Endokrynol Pol. 2010;61(3):260-3.
  10. Dreval’ AV, Trigolosova IV, Wolffenbuttel BHR, Misnikova IV, Kovalyova YuA, Tishenina RS, Barsukov IA, Vinogradova AV. Prevalence of carbohydrate metabolism disorders in patients with acromegaly. 49th European Association for the study of Diabetes 2013 23-27 September 2013, Barselona, Spain, Diabetologia. 2013;56 Suppl 1:S1-S566
  11. Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf). 1994;41(1):95-102.
  12. Dreval’ AV, Trigolosova IV, Misnikova IV, Kovalyova YA, Tishenina RS, Barsukov IA, Vinogradova AV, Wolffenbuttel BH. Prevalence of diabetes mellitus in patients with acromegaly. Endocr Connect. 2014;3(2):93-8.
  13. Fieffe S, Morange I, Petrossians P, Chanson P, Rohmer V, Cortet C, Borson-Chazot F, Brue T, Delemer B; French Acromegaly Registry. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol. 2011;164(6):877-84.
  14. Nabarro JD. Acromegaly. Clin Endocrinol (Oxf). 1987;26(4):481- 512.
  15. Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009;30(2):152-77.
  16. Foss MC, Saad MJ, Paccola GM, Paula FJ, Piccinato CE, Moreira AC. Peripheral glucose metabolism in acromegaly. J Clin Endocrinol Metab. 1991;72(5):1048-53.
  17. Muggeo M, Saviolakis GA, Businaro V, Valerio A, Moghetti P, Crepaldi G. Insulin receptor on monocytes from patients with acromegaly and fasting hyperglycemia. J Clin Endocrinol Metab. 1983;56(4):733-8.
  18. Pratipanawatr T, Pratipanawatr W, Rosen C, Berria R, Bajaj M, Cusi K, Mandarino L, Kashyap S, Belfort R, DeFronzo RA. 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.
  19. Luft R, Cerasi E, Hamberger CA. Studies on the pathogenesis of diabetes in acromegaly. Acta Endocrinol (Copenh). 1967;56(4): 593-607.
  20. Древаль АВ, Триголосова ИВ, Виноградова АВ, Иловайская ИА, Тишенина РС. Особенности нарушений углеводного обмена при акромегалии в зависимости от проводимого лечения. Ожирение и метаболизм. 2013;(4):21-25. (Dreval’ AV, Trigolosova IV, Vinogradova AV, Ilovayskaya IA, Tishenina RS. [The features of the carbohydrate metabolism disturbances in acromegaly patients depending on the treatment used]. Ozhirenie i metabolism. 2013;(4):21-25. Russian).
  21. Pereira AM, Biermasz NR, Roelfsema F, Romijn JA. Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance. Treat Endocrinol. 2005;4(1): 43-53.
  22. Colao A, Pivonello R, Galderisi M, Cappabianca P, Auriemma RS, Galdiero M, Cavallo LM, Esposito F, Lombardi G. Impact of treating acromegaly first with surgery or somatostatin analogs on cardiomyopathy. J Clin Endocrinol Metab. 2008; 93(7):2639-46.
  23. Ronchi CL, Varca V, Beck-Peccoz P, Orsi E, Donadio F, Baccarelli A, Giavoli C, Ferrante E, Lania A, Spada A, Arosio M. Comparison between six-year therapy with long-acting somatostatin analogs and successful surgery in acromegaly: effects on cardiovascular risk factors. J Clin Endocrinol Metab. 2006;91(1):121-8.
  24. Zambre Y, Ling Z, Chen MC, Hou X, Woon CW, Culler M, Taylor JE, Coy DH, Van Schravendijk C, Schuit F, Pipeleers DG, Eizirik DL. 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.
  25. Singh V, Brendel MD, Zacharias S, Mergler S, Jahr H, Wiedenmann B, Bretzel RG, Plöckinger U, Strowski MZ. 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.
  26. Steffin B, Gutt B, Bidlingmaier M, Dieterle C, Oltmann F, Schopohl J. Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly. Eur J Endocrinol. 2006;155(1):73-8.
  27. 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.
  28. Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M, Fleseriu M, van der Lely AJ, Farrall AJ, Hermosillo Reséndiz K, Ruffin M, Chen Y, Sheppard M; Pasireotide C2305 Study Group. Pasireotide Versus Octreotide in Acromegaly: A Head-to-Head Superiority Study. J Clin Endocrinol Metab. 2014;99(3):791-9.
  29. Schmid HA, Brueggen J. Effects of somatostatin analogs on glucose homeostasis in rats. J Endocrinol. 2012;212(1):49-60.
  30. Jørgensen JO, Feldt-Rasmussen U, Frystyk J, Chen JW, Kristensen LØ, Hagen C, Ørskov H. Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist. J Clin Endocrinol Metab. 2005;90(10):5627-31.
  31. Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005;90(10):5684-91. 3
  32. Cambuli VM, Galdiero M, Mastinu M, Pigliaru F, Auriemma RS, Ciresi A, Pivonello R, Amato M, Giordano C, Mariotti S, Colao A, Baroni MG. Glycometabolic control in acromegalic patients with diabetes: a study of the effects of different treatments for growth hormone excess and for hyperglycemia. J Endocrinol Invest. 2012;35(2):154-9.
  33. Ali O, Banerjee S, Kelly DF, Lee PD. Management of type 2 diabetes mellitus associated with pituitary gigantism. Pituitary. 2007;10(4):359-64.
  34. Colao A, Auriemma RS, Savastano S, Galdiero M, Grasso LF, Lombardi G, Pivonello R. Glucose tolerance and somatostatin analog treatment in acromegaly: a 12-month study. J Clin Endocrinol Metab. 2009;94(8):2907-14.
  35. Larijani B, Nakhjavani M, Baradar-Jalili R, Akrami SM, Bandarian F. Diabetes mellitus following pituitary adenomectomy in euglycemic patients with acromegaly. J Coll Physicians Surg Pak. 2005;15(7):430-2.
  36. Tolis G, Angelopoulos NG, Katounda E, Rombopoulos G, Kaltzidou V, Kaltsas D, Protonotariou A, Lytras A. Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs. Neuroendocrinology. 2006;83(3-4): 249-57.
  37. Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JA, Giustina A. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013;16(3):294-302.
  38. Erfurth EM, Hagmar L. Cerebrovascular disease in patients with pituitary tumors. Trends Endocrinol Metab. 2005;16(7):334- 42.
  39. Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997;46(1):75-81.
  40. Verhelst J, Abs R. Long-term growth hormone replacement therapy in hypopituitary adults. Drugs. 2002;62(16):2399-412.
  41. Abs R, Mattsson AF, Thunander M, Verhelst J, Góth MI, Wilton P, Kołtowska-Häggström M, Luger A. Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis. Eur J Endocrinol. 2013;168(3):297-305.
  42. Attanasio AF, Jung H, Mo D, Chanson P, Bouillon R, Ho KK, Lamberts SW, Clemmons DR; HypoCCS International Advisory Board. Prevalence and incidence of diabetes mellitus in adult patients on growth hormone replacement for growth hormone deficiency: a surveillance database analysis. J Clin Endocrinol Metab. 2011;96(7):2255-61.
  43. Jørgensen JO, Møller J, Alberti KG, Schmitz O, Christiansen JS, Orskov H, Moller N. Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects. J Clin Endocrinol Metab. 1993;77(6):1589-96.
  44. Fowelin J, Attvall S, Lager I, Bengtsson BA. Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency. Metabolism. 1993;42(11):1443-7.
  45. O’Neal DN, Kalfas A, Dunning PL, Christopher MJ, Sawyer SD, Ward GM, Alford FP. The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucosemediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis. J Clin Endocrinol Metab. 1994;79(4):975-83.
  46. Rosenfalck AM, Fisker S, Hilsted J, Dinesen B, Vølund A, Jørgensen JO, Christiansen JS, Madsbad S. The effect of the deterioration of insulin sensitivity on beta-cell function in growth-hormone-deficient adults following 4-month growth hormone replacement therapy. Growth Horm IGF Res. 1999;9(2):96-105.
  47. Hoybye C, Jönsson P, Monson JP, Koltowska-Häggström M, Hána V, Geffner M, Abs R. Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency. Eur J Endocrinol. 2007;157(5):589-96.
  48. Elbornsson M, Götherström G, Bosæus I, Bengtsson BÅ, Johannsson G, Svensson J. Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol. 2013;168(5):745-53.
  49. Mancini T, Kola B, Mantero F, Boscaro M, Arnaldi G. High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol (Oxf). 2004;61(6):768-77.
  50. Feelders RA, Pulgar SJ, Kempel A, Pereira AM. The burden of Cushing’s disease: clinical and health-related quality of life aspects. Eur J Endocrinol. 2012;167(3):311-26.
  51. Giordano C, Guarnotta V, Pivonello R, Amato MC, Simeoli C, Ciresi A, Cozzolino A, Colao A. Is diabetes in Cushing’s syndrome only a consequence of hypercortisolism? Eur J Endocrinol. 2013;170(2):311-9.
  52. Pecori Giraldi F, Moro M, Cavagnini F; Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of Endocrinology. Gender-related differences in the presentation and course of Cushing’s disease. J Clin Endocrinol Metab. 2003;88(4):1554-8.
  53. Белая ЖЕ, Рожинская ЛЯ, Драгунова НВ, Дзеранова ЛК, Марова ЕИ. Метаболические осложнения эндогенного гиперкортицизма. Выбор пациентов для скрининга. Ожирение и метаболизм. 2013;(1):26-30. (Belaya ZhE, Rozhinskaya LYa, Dragunova NV, Dzeranova LK, Marova EI. [Metabolic complications of endogenous Cushing: patient selection for screening]. Ozhirenie i metabolism. 2013;(1):26-30. Russian).
  54. Дзеранова ЛК, Панкратова ЮВ, Белая ЖЕ, Пигарова ЕА, Манченко ОВ, Рожинская ЛЯ, Григорьев АЮ, Колесникова ГС. Гиперкортицизм и метаболический синдром: сложности дифференциальной диагностики и лечения. Ожирение и метаболизм. 2012;(31):57-61. (Dzeranova LK, Pankratova YuV, Belaya ZhE, Pigarova EA, Manchenko OV, Rozhinskaya LYa, Grigor’ev AYu, Kolesnikova GS. [Hypercortisolism and metabolic syndrome: the complexities of the differential diagnosis and treatment]. Ozhirenie i metabolism. 2012;(12):57-61. Russian).
  55. Vander Kooi BT, Onuma H, Oeser JK, Svitek CA, Allen SR, Vander Kooi CW, Chazin WJ, O’Brien RM. The glucose-6-phosphatase catalytic subunit gene promoter contains both positive and negative glucocorticoid response elements. Mol Endocrinol. 2005;19(12):3001-22.
  56. Ruzzin J, Wagman AS, Jensen J. Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor. Diabetologia. 2005;48(10):2119-30.
  57. Resmini E, Minuto F, Colao A, Ferone D. Secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. Acta Diabetol. 2009;46(2):85-95.
  58. Hansen KB, Vilsbøll T, Bagger JI, Holst JJ, Knop FK. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects. J Clin Endocrinol Metab. 2010;95(7):3309-17.
  59. Терехин СА, Перетокина ЕВ, Бондаренко ИЗ. Особенности клинического течения сахарного диабета у пациента после лечения болезни Иценко-Кушинга. Сахарный диабет. 2012;(1):81-86. (Terekhin SA, Peretokina EV, Bondarenko IZ. [Peculiarities of diabetes mellitus clinical course in a patient after Cushing’s disease treatment]. Sakharnyy diabet. 2012;(1):81-86. Russian).

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2014 Trigolosova I.V., Vinogradova A.V., Kruglyakova M.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies