Characteristics of insulin therapy of diabetes mellitus type 1 in children and adolescents receiving glucocorticoids

BACKGROUND: In coexistence of diabetes mellitus type 1 (DM1) with severe autoimmune and inflammatory diseases some patients need simultaneous administration of insulin and glucocorticoids (GC). GC therapy in patients with DM1 can worsen glycemic control.

AIM: To determine characteristics of insulin therapy of DM1 in children and adolescents receiving GC.

DESCRIPTION OF CLINICAL CASES: We observed 5 patients with DM1 receiving GC for juvenile idiopathic arthritis (JIA), juvenile systemic sclerosis (JSS), juvenile dermatomyositis (JDM), ulcerative colitis (UC), and reactive arthritis (RA).

Intra-articular administration of GC did not significantly influence glycemic control.

In case of GC pulse therapy hyperglycemia and increased insulin requirements were recognized in 3–6 hours after GC receipt, persisted from few hours up to 3 days after each administration.

While therapy with oral GC in high doses the worst glycemic control was registered in daylight hours. To overcome insulin resistance change of time of injection and 10%-increase of long-acting insulin analogue, additional injections of ultrashort-acting insulin analogues, temporal prescription of short-acting human insulin were used.

While GC therapy insulin daily dose was individual and could reach 2.0 U/kg. After transition to maintaining doses of GC or discontinuation of GC therapy patients returned to standard or relatively low insulin requirements.

Levels of glycosylated hemoglobin differed significantly among patients at different stages of treatment, were maximal while long-term therapy with high doses of oral GC, but mostly depended on patient’s compliance.

CONCLUSION: Bettering of glycemic control while receiving GC can be reached by timely dose correction of insulin therapy, selection of individual schemes, taking into account time of receipt and pharmacokinetic characteristics of GC. Adherence of the patient and his family to treatment of DM1 plays an important role in glycemic control.

diabetes mellitus, children, glucocorticoids

1. Федеральные клинические рекомендации (протоколы) по ведению детей с эндокринными заболеваниями. / Под ред. Дедова И.И., Петерковой В.А. — М.: Практика; 2014. [Dedov II, Peterkova VA, editors. Federal’nye klinicheskie rekomendatsii (protokoly) po vedeniyu detey s endokrinnymi zabolevaniyami. Moscow: Praktika; 2014. (In Russ.)]

2. Дедов И.И., Шестакова М.В., и др. Сахарный диабет в Российской Федерации: распространенность, заболеваемость, смертность, параметры углеводного обмена и структура сахароснижающей терапии по данным Федерального регистра сахарного диабета, статус 2017 г. // Сахарный диабет. — 2018. — Т. 21. — №3. — С. 144-159. [Dedov II, Shestakova MV, Vikulova OK, et al. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017. Diabetes mellitus. 2018;21(3):144-159. (In Russ.)] https://doi.org/10.14341/DM9686

3. Руководство по детской ревматологии. / Под ред. Геппе Н.А., Подчерняевой Н.С., Лыскиной Г.А. — М.: ГЭОТАР-Медиа; 2011. [Geppe NA, Podchernyaeva NS, Lyskina GA, editors. Rukovodstvo po detskoy revmatologii. Moscow: GEOTAR-Media; 2011. (In Russ.)]

4. Jannot-Lamotte MF, Raccah D. Management of diabetes during corticosteroid therapy. Presse Med. 2000;29(5):263-266.

5. Hermann G, Thon A, Monkemoller K, et al. Comorbidity of type 1 diabetes and juvenile idiopathic arthritis. J Pediatr. 2015;166(4):930-935 e931-933. https://doi.org/10.1016/j.jpeds.2014.12.026

6. Emamifar A, Levin K, Jensen Hansen IM. Patients with newly diagnosed rheumatoid arthritis are at increased risk of diabetes mellitus: an observational cohort study. Acta Reumatol Port. 2017;42(4):310-317.

7. Pohjankoski H, Kautiainen H, Korppi M, Savolainen A. Simultaneous juvenile idiopathic arthritis and diabetes mellitus type 1 -- a Finnish nationwide study. J Rheumatol. 2012;39(2):377-381. https://doi.org/10.3899/jrheum.110654

8. Tseng CC, Chang SJ, Tsai WC, et al. Reduced incidence of Type 1 diabetes and Type 2 diabetes in systemic sclerosis: A nationwide cohort study. Joint Bone Spine. 2016;83(3):307-313. https://doi.org/10.1016/j.jbspin.2015.06.017

9. Pavlovic MD, Milenkovic T, Dinic M, et al. The prevalence of cutaneous manifestations in young patients with type 1 diabetes. Diabetes Care. 2007;30(8):1964-1967. https://doi.org/10.2337/dc07-0267

10. Yosipovitch G, Hodak E, Vardi P, et al. The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes Care. 1998;21(4):506-509. https://doi.org/10.2337/diacare.21.4.506

11. Алексеева Е.И., Маслиева Р.И., Лыскина Г.А., Бзарова Т.М. Федеральные клинические рекомендации по оказанию медицинской помощи детям с ювенильным дерматомиозитом. / Под ред. Баранова А.А. — 2015. [Alekseeva ЕI, Maslieva RI, Lyskina GA, Bzarova TM. Baranov AA, editor. Federal’nye klinicheskie rekomendatsii po okazaniyu meditsinskoy pomoshchi detyam s yuvenil’nym dermatomiozitom. 2015. (In Russ.)]

12. Kosik VN. A combination of diabetes mellitus and dermatomyositis. Vrach Delo. 1969;9:143.

13. Sattar MA, Al-Sughyer AA, Siboo R. Coexistence of Rheumatoid Arthritis, Ankylosing Spondylitis and Dermatomyositis in a Patient with Diabetes Mellitus and the Associated Linked Hla Antigens. Rheumatology. 1988;27(2):146-149. https://doi.org/10.1093/rheumatology/27.2.146

14. Singh R, Cuchacovich R, Gomez R, et al. Simultaneous occurrence of diabetes mellitus and juvenile dermatomyositis: report of two cases. Clin Pediatr (Phila). 2003;42(5):459-462. https://doi.org/10.1177/000992280304200514

15. Charalabopoulos K, Charalabopoulos A, Papaioannides D. Diabetes mellitus type I associated with dermatomyositis: an extraordinary rare case with a brief literature review. BMJ Case Rep. 2009;2009. https://doi.org/10.1136/bcr.10.2008.1158

16. McClanahan CM, Smith HL, Garner SA. Co-occurrence of dermatomyositis and Hashimoto’s thyroiditis in a type I diabetic patient. QJM. 2015;108(4):331-333. https://doi.org/10.1093/qjmed/hcs152

17. Benchimol EI, Fortinsky KJ, Gozdyra P, et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011;17(1):423-439. https://doi.org/10.1002/ibd.21349

18. Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr. 2005;146(1):35-40. https://doi.org/10.1016/j.jpeds.2004.08.043

19. Потапов АС, Алиева ЭИ, Габрузская ТВ, и др. Клиническая картина, диагностика и лечение язвенного колита у детей: Российский педиатрический консенсус (репринт) // Вопросы современной педиатрии. — 2013. — Т. 12. — №3. — С. 1-9. [Potapov AS, Alieva EI, Gabruzskaya TV, et al. Clinical manifestation, diagnostics and treatment of ulcerative colitis in children: russian pediatric consensus. Current Pediatrics. 2013;12(3):18-30. (In Russ.)] https://doi.org/10.15690/vsp.v12i3.677

20. Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014;8(10):1179-1207. https://doi.org/10.1016/j.crohns.2014.04.005

21. Jasser-Nitsche H, Bechtold -Dalla Pozza S, Binder E, et al. Inflammatory bowel disease in children and adolescents with type 1 diabetes: a multicenter analysis from the German-Austrian DPV database. Pediatr diabetes. 2016,17(S24):2.

22. Zarkovic M, Beleslin B, Ciric J, et al. Glucocorticoid effect on insulin sensitivity: a time frame. J Endocrinol Invest. 2008;31(3):238-242. https://doi.org/10.1007/BF03345596

23. Bevier WC, Zisser HC, Jovanovic L, et al. Use of continuous glucose monitoring to estimate insulin requirements in patients with type 1 diabetes mellitus during a short course of prednisone. J Diabetes Sci Technol. 2008;2(4):578-583. https://doi.org/10.1177/193229680800200408

24. Spanakis EK, Shah N, Malhotra K, et al. Insulin requirements in non-critically ill hospitalized patients with diabetes and steroid-induced hyperglycemia. Hosp Pract. 2014;42(2):23-30. https://doi.org/10.3810/hp.2014.04.1100