Glucose metabolism during androgen deprivation therapy with GNRH agonists


DOI: https://dx.doi.org/10.18565/therapy.2020.8.36-46

Demidova T.Yu., Gritskevich E.Yu., Maturov M.R., Bystrov A.A.

1) N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia, Moscow; 2) D.D. Pletnev Municipal Clinical Hospital of Moscow Healthcare Department; 3) Moscow Municipal Oncology Hospital No. 62 of Moscow Healthcare Department
Purpose: to study the impact of gonadotropin-releasing hormone agonists (aGnRH) in patients with locally advanced prostate cancer (PCa) on the parameters of carbohydrate metabolism.
Materials and methods. The study included 102 patients with PCa, receiving androgen-deprivation therapy (ADT) with aGnRH, 99 people completed it. Their average age was 69,11±8,64 years. To assess glucose metabolism, the level of glycohemoglobin (HbA1c), fasting plasma glucose (FPG) was studied before the start of ADT, after 3, 6 and 12 months from the start of therapy. For a more detailed determination of the patterns of daily changes in glycemia, 10 patients were installed with Flash glucose monitoring systems, which allow obtaining data of the «ambulatory glycemic profile», the following indices of variability were calculated to calculate the variability indices: AUC, MAGE, CONGA, J-index and HGBI.
Results. The following changes in the studied parameters were recorded: Metabolic parameters at baseline, after 3, 6 and 12 months, respectively: HbA1c 5,36%, 5,66 (+5,5%), 5,77 (+7,5%), 5,89 (+9,9%); fasting plasma glucose 5,18 ммоль/л, 5,67 (+9,5%), 5,77 (+11,4%), 5,90 (+13,9%) (for all differences p <0,05). According to Flash-monitoring data, early disorders of glucose metabolism were revealed: basal glycemic values ​​exceed 5,6 mmol/l, prandial peaks are higher than 7,8 mmol/l, and variability indices are higher than those of healthy persons of similar age, and CONGA exceeds the recommended value for patients with diabetes mellitus.
Conclusion. It was found that continuous ADT by GnRH agonists is accompanied by a permanent progressive deterioration of glucose metabolism indicators: fasting plasma glucose, HbA1c, glycemic variability. These disorders are early – their maximum change falls on the first 3 months of therapy. However, further, during the year, the increase in indicators remains, in connection with which there is a transition of early forms of carbohydrate metabolism disorders into the category of diabetes mellitus. It is necessary to further study the metabolic consequences of ADT and expand knowledge about the timing, conditions and risk factors of their development to determine the timing of potential intervention in order to prevent the negative consequences of ADT.
Keywords: glucose metabolism, glycemic variability, gonadotropin-releasing hormone agonists, prostate cancer
Read entire article

Literature


  1. Stellato R.K., Feldman H.A., Hamdy O. et al. Testosterone, sex hormonebinding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000; 23(4): 490–94. doi: 10.2337/diacare.23.4.490.

  2. Oh J.Y., Barrett-Connor E., Wedick N.M. et al. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care. 2002; 25(1): 55–60. doi: 10.2337/diacare.25.1.55.

  3. Алексеев Б.Я., Нюшко К.М., Каприн А.Д. Аналоги лютеинизирующего гормона рилизинг-гормона в терапии больных раком предстательной железы. Медицинский совет. 2018; 19: 96–100. [Alekseev B.Ya., Nyushko K.M., Kaprin A.D. Analogs of luteinizing hormone releasing hormone in the treatment of patients with prostate cancer. Meditsinskiy sovet. 2018; 19: 96–100 (In Russ.)]. doi: 10.21518/2079-701X-2018-19-96-100.

  4. Ferlay J., Colombet M., Soerjomataram I. еt al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019; 144(8): 1941–53. doi: 10.1002/ijc.31937.

  5. Состояние онкологической помощи населению России в 2018 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М. 2019. [The state of cancer care for the population of Russia in 2018. Ed. by Kaprin, V.V. Starinsky, G.V. Petrova. M. 2019 (In Russ.)].

  6. Keating N.L., O’Malley A.J., Freedland S.J. et al. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2010; 102(1): 39–46. doi: 10.1093/jnci/djp404.

  7. Alibhai S.M., Duong-Hua M., Sutradhar R. et al. Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clin Oncol. 2009; 27(21): 3452–58. doi: 10.1200/JCO.2008.20.0923.

  8. Jespersen C.G., Norgaard M., Borre M. Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur Urol. 2014; 65(4): 704–09. doi: 10.1016/j.eururo.2013.02.002.

  9. Smith J.C., Bennett S., Evans L.M. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab. 2001; 86(9): 4261–67. doi: 10.1210/jcem.86.9.7851.

  10. Smith M.R., Finkelstein J.S., McGovern F.J. et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin EndocrinolMetab. 2002; 87(2): 599–603. doi: 10.1210/jcem.87.2.8299.

  11. Smith M.R., Lee H., Nathan D.M. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006; 91(4): 1305–08. doi: 10.1210/jc.2005-2507.

  12. Basaria S., Muller D.C., Carducci M.A. et al. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen deprivation therapy. Cancer. 2006; 106(3): 581–88. doi: 10.1002/cncr.21642.

  13. Keating N.L., O’Malley A.J., Smith M.R. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006; 24(27): 4448–56. doi: 10.1200/JCO.2006.06.2497.

  14. Nguyen P.L., Alibhai S.M., Basaria S. et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015; 67(5): 825–36. doi: 10.1016/j.eururo.2014.07.010.

  15. Inaba M., Otani Y., Nishimura K. et al. Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. Metabolism. 2005; 54(1): 55–59. doi: 10.1016/j.metabol.2004.07.010.

  16. Mauvais-Jarvis F. Role of sex steroids in β cell function, growth, and survival. Trends Endocrinol Metab. 2016; 27(12): 844–55. doi: 10.1016/j.tem.2016.08.008.

  17. Mauvais-Jarvis F. Androgen-deprivation therapy and pancreatic β-cell dysfunction in men. J Diabetes Complications. 2016; 30(3): 389–90. doi: 10.1016/j.jdiacomp.2016.01.007.

  18. Heianza Y., Arase Y., Fujihara K. et al. Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA(1c) and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4). Diabet Med. 2012; 29(9): 279–85. doi: 10.1111/j.1464-5491.2012.03686.x.

  19. Mitsuzuka K., Kyan A., Sato T. et al. Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer. Prostate Cancer Prostatic Dis. 2016; 19(1): 57–62. doi: 10.1038/pcan.2015.50.

  20. Angelantonio E., Ingelsson E., Lawlor D.A. et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010; 375(9733): 2215–22. doi: 10.1016/S0140-6736(10)60484-9.

  21. Vistisen D., Witte D.R., Brunner E.J. et al. Risk of cardiovascular disease and death in individuals with prediabetes defined by different criteria: the Whitehall II study. Diabetes Care. 2018; 41(4): 899–906. doi: 10.2337/dc17-2530.


About the Autors

Tatyana Yu. Demidova, MD, professor, head of the Department of endocrinology, faculty of general medicine of N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 109263, Moscow, 4/1 Shkuleva Str. E-mail: t.y.demidova@gmail.com. ORCID: 0000-0001-6385-540X. Scopus Author ID: 7003771623. eLIBRARY.RU SPIN: 9600-9796
Elena Yu. Gritskevich, assistant of the Department of endocrinology, faculty of general medicine of N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 109263, Moscow, 4/1 Shkuleva Str. E-mail: genyan.7@mail.ru. ORCID: 0000-0002-0086-869X. eLIBRARY.RU SPIN: 4125-2055
Mikhail R. Maturov, oncologist of D.D. Pletnev Municipal Clinical Hospital of Moscow Healthcare Department. Address: 105264, Moscow, 29 Verkhnyaya Pervomayskaya. E-mail: mihail.maturov@yandex.ru
Alexander A. Bystrov, PhD, oncologist of Moscow Municipal Oncology Hospital No. 62 of Moscow Healthcare Department (outpatient unit). Address: 125130, Moscow, 6/2 Staropetrovsky passage. E-mail: bystrov@list.ru


Similar Articles

Back to Content

Бионика Медиа