pp 1-14 | Cite as

Pharmacotherapy of Children and Adolescents with Type 1 Diabetes Mellitus

  • Thomas M. KapellenEmail author
Part of the Handbook of Experimental Pharmacology book series


Insulin treatment in children and adolescents with autoimmune type 1 diabetes has changed tremendously in the last 20 years with the knowledge of DCCT trial regarding near-normal glucose levels on the micro- and macrovascular outcome. Intensified insulin therapy is now standard of care. Carb counting however was introduced systematically only recently in several countries. In industrialized countries most patients in this age group are treated with continuous subcutaneous insulin injections. Nowadays this is combined with continuous subcutaneous glucose measurement commencing sensor-augmented pump therapy. Predictive low glucose suspend reduces the frequency of hypoglycemic events. Still not available for children is a commercially available closed loop system. However, treatment goals are still frequently not reached especially in the group of adolescents. Therefore several additive drugs are tested to improve treatment results. There are new insulins with faster and longer action profile in the pipeline to better mimic physiologic insulin profiles. Smart insulins may be able to mimic reaction on blood sugar levels. The broad facet of treatment modalities helps pediatric diabetes teams to individualize therapy and so improve patients’ health-related quality of life.


Adolescents Children CSII Insulin treatment Long-acting insulin Rapid-acting insulin Sensor-augmented pump therapy 


  1. Abali S, Turan S, Atay Z, Güran T, Haliloglu B, Bereket A (2015) Higher insulin detemir doses are required for the similar glycemic control: comparison of insulin detemir and glargine in children with type 1 diabetes mellitus. Pediatr Diabetes 16:361–366Google Scholar
  2. Anderson G, Meiffren G, Lamers D, DeVries JH, Ranson A, Seroussi C, Alluis B, Gaudier M, Soula O, Heise T (2018) Ultra-rapid BioChaperone Lispro improves postprandial blood glucose excursions vs lispro in a 14-day crossover treatment study in people with type 1 diabetes. Diabetes Obes Metab 20:2627–2632Google Scholar
  3. Bachran R, Beyer P, Klinkert C, Heidtmann B, Rosenbauer J, Holl RW (2012) Basal rates and circadian profiles in continuous subcutaneous insulin infusion (CSII) differ for preschool children, prepubertal children, adolescents and young adults. Pediatr Diabetes 13:1–5Google Scholar
  4. Beato-Vibora PI, Quiros-Lopez C, Lazaro-Martin L, Martin-Frias M, Barrio-Castellanos R, Gil-Poch E, Arroyo-Diez FJ, Gimenez-Alvarez M (2018) Impact of sensor-augmented pump therapy with predictive low glucose suspend function on glycemic control and patient satisfaction in adults and children with type 1 diabetes. Diabetes Technol Ther 20:738–743Google Scholar
  5. Bendas A, Rothe U, Kiess W, Kapellen TM, Stange T, Manuwald U et al (2015) Trends in incidence rates during 1999-2008 and prevalence in 2008 of childhood type 1 diabetes mellitus in Germany-model based national estimates. PLoS One 16:10Google Scholar
  6. Bergenstal RM, Tamborlane W, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Peoples T, Perkins BA, Welsh JB, Willi SM, Wood MA, STAR 3 Study Group (2010) Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med 363:311–320Google Scholar
  7. Bergenstal RM, Bailey TS, Rodbard D, Ziemen M, Guo H, Muehlen-Bartmer I, Ahmann AJ (2017) Comparison of insulin glargine 300 units/mL and 100 units/m Lind adults with type 1 diabetes: continuous glucose monitoring profiles and variability using morning and evening injections. Diabetes Care 40:554–560Google Scholar
  8. Burdik P, Cooper S, Horner B, Cobry E, McFann K, Chase HP (2009) Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes. Pediatr Diabetes 10:116–119Google Scholar
  9. Danne T, Aman J, Schober E, Deiss D, Jacobsen JL, Friberg HH, Jensen LH, ANA 1200 Study Group (2003) A comparison of postprandial and preprandial administration of insulin aspart in children and adolescents with type 1 diabetes mellitus. Diabetes Care 26:2359–2364Google Scholar
  10. Danne T, Philotheou A, Goldman D, Guo X, Cali A, Johnston P (2013) A randomized trial comparing the rate of hypoglycemia – assessed using continuous glucose monitoring – in 125 preschool children with type 1 diabetes treated with insulin glargine or NPH insulin (the PRESCHOOL study). Pediatr Diabetes 14:593–601Google Scholar
  11. Danne T, Phillip M, Buckingham BA, Jarosz-Chobot P, Saboo B, Urakami T, Battelino T, Hanas R, Codner E (2018) ISPAD clinical practice guidelines 2018: insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 19(Suppl 27):115–135Google Scholar
  12. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. N Engl J Med 329:977–986Google Scholar
  13. Engwerda EE, Tack CJ, de Galan BE (2017) Pharmacokinetic and pharmacodynamic variability of insulin when administered by jet injection. J Diabetes Sci Technol 11:947–952Google Scholar
  14. Fath M, Danne T, Biester T, Erichsen L, Kordonouri O, Haahr H (2017) Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes 18:903–910Google Scholar
  15. Forlenza GP, Pinhas-Hamile O, Liljenquist DR, Shulman DI, Bailey TS, Bode BW, Wood MA, Buckingham BA, Kaiserman KB, Shin J, Huang S, Lee SW, Kaufman FR (2019) Safety evaluation of the MiniMed 670G system in children 7-13 years of age with type 1 diabetes. Diabetes Technol Ther 21:11–19Google Scholar
  16. Fullerton B, Siebenhofer A, Jeitler K, Horvath K, Semlitsch T, Berghold A, Plank J, Pieber TR, Gerlach FM (2016) Short acting insulin analogues versus regular human insulin for adults with type 1 diabetes. Cochrane Database Syst Rev:CD012161Google Scholar
  17. Heise T, Pieber TR, Danne T, Erichsen L, Haahr H (2017) Pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes. Clin Pharmacokinet 56:551–559Google Scholar
  18. Holl RW, Prinz N (2019) Versorgung von Kindern und Jugendlichen mit Diabetes – aktuelle Situation und Veränderungen der letzten 23 Jahre. In: Deutscher Gesundheitsbericht Diabetes 2019. Herausgeber Deutsche Diabetesgesellschaft. Kirchheim Verlag, Mainz. ISSN 1614-824XGoogle Scholar
  19. Home PD (2012) The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. Diabetes Obes Metab 14:780–788Google Scholar
  20. Kapellen TM, Dost A, Leludas C, Kiess W (1998) Patient acceptance and use of an emergency telephone hotline service in pediatric diabetes care. Diabetes Care 21:1365Google Scholar
  21. Kapellen TM, Gausche R, Dost A, Wiegand S, Flechtner-Mors M, Keller E, Kiess W, Holl RW, for the DPV-Science-Initiative of the German Competence Network Diabetes and the German Competence Network Obesity (Consortium LARGE) (2013) Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database. J Pediatr Endocrinol Metab 7:1–6Google Scholar
  22. Kapellen TM, Heidtmann B, Lilienthal E, Rami-Merhar B, Engler-Schmidt C, Holl RW (2015) Continuous subcutaneous insulin infusion in neonates and infants below 1 year: analysis of initial bolus and basal rate based on the experiences from the German working group for pediatric pump treatment. Diabetes Technol Ther 17:872–879Google Scholar
  23. Karges B, Schwandt A, Heidtmann B, Kordonouri O, Binder E, Schierloh U, Boettcher C, Kapellen T, Rosenbauer J, Holl RW (2017) Association of insulin pump therapy versus insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes. JAMA 318:1358–1366Google Scholar
  24. Khalifah RA, Alnhdi A, Alghar H, Alanazi M, Florez ID (2017) The effect of adding metformin to insulin therapy for type 1 diabetes mellitus children: a systematic review and metaanalysis. Pediatr Diabetes 18:664–673Google Scholar
  25. Laranjeira FO, de Anrade KR, Figueiredo AC, Silva EN, Pereira MG (2018) Long acting insulin analogues for type 1 diabetes: an overview of systematic reviews and meta-analysis of randomized controlled trials. PLoS One 13:e0194801Google Scholar
  26. Libman IM, Miller KM, DiMeglio LA, Bethin KE, Katz ML, Shah A, Simmons JH, Haller MJ, Raman S, Tamborlane WV, Coffey JK, Saenz AM, Beck RW, Nadeau KJ, for the T1D Exchange Clinic Network Metformin RCT Study Group (2015) Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes. JAMA 314(21):2241–2250Google Scholar
  27. Lucidi P, Porcellati F, MarinelliAndreoli A, Carriero I, Cioli P, Bolli GB, Fanelli CG (2015) Pharmacokinetics and pharmacodynamics of NPH in Type 1 diabetes: the importance of appropriate resuspension before subcutaneous injection. Diabetes Care 38:2204–2210Google Scholar
  28. Meyer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME (2018) ISPAD clinical practice guidelines 2018: definition, epidemiology and classification of diabetes in children and adolescents. Pediatr Diabetes 19(Suppl 27):7–19Google Scholar
  29. Mueller-Godeffroy E, Vonthein R, Ludwig-Seibold C, Heidtmann B, Boettcher C, Kramer M, Hessler N, Hilgard D, Lilienthal E, Ziegler A, Wagner VM, on behalf of the German working group for Pediatric Pump Therapy (agip) (2018) Psychosocial benefits of insulin pump therapy in children with type 1 diabetes and their families: the pumpkin multicenter randomized controlled trial. Pediatr Diabetes 19:1471–1480Google Scholar
  30. Neal B, Perkovic V, Mahaffey KW, CANVAS Program Collaborative Group et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377:644–657Google Scholar
  31. Päivärinta M, Tapainen P, Veijola R (2008) Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes. Pediatr Diabetes 9:83–90Google Scholar
  32. Petrie JR, Chaturvedi N, Ford I, Brouwers MC, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein EK, Klein R, Ooi TC, Rossing P, Stehouwer CD, Sattar N, Colhoun HM, on behalf of REMOVAL Study Group (2017) Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 5:597–609Google Scholar
  33. Philotheou A, Arslanian S, Blatniczky L, Peterkova V, Souhami E, Danne T (2011) Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of basal bolus regimen in a 26-week trial in pediatric patients with type 1 diabetes. Diabetes Technol Ther 13:327–334Google Scholar
  34. Quianzon CC, Cheikh I (2012) History of insulin. J Community Hosp Intern Med Perspect 2(2). Scholar
  35. Riddle MC, Cefalu WT (2018) SGLT inhibitors for type 1 diabetes: an obvious choice or too good to be true? Diabetes Care 41:2444–2447Google Scholar
  36. Sherr JL, Hermann JM, Campbell F, Foster NC, Hofer SE, Allgrove J, Maahs DM, Kapellen TM, Holman N, Tamborlane WV, Holl RW, Beck RW, Warner JT (2016) Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large transatlantic paediatric registries. Diabetologia 59:87–91Google Scholar
  37. Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shan VN, Leelaranthna L, Hovorka R, APCam11 Consortium (2018) Closed loop delivery in suboptimal controlled type 1 diabetes: a multicentre, 12 week randomized trial. Lancet 392:1321–1329Google Scholar
  38. Thalange N, Bereket A, Larsen J, Hiort LC, Peterkova V (2013) Insulin analogues in children with type 1 diabetes: a 52-week randomized clinical trial. Diabet Med 30:216–225Google Scholar
  39. Thelange N, Deeb L, Iotova V, Kawamura T, Klingensmith G, Philotheou A, Silverstein J, Tumini S, Ocampo Francisco A-M, Kinduryte O, Danne T (2015) Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes. Pediatr Diabetes. 16:164–176Google Scholar
  40. Tosur M, Redondo MJ, Lyons SK (2018) Adjuvant pharmacotherapies to insulin for the treatment of type 1 diabetes. Curr Diab Rep 18:79Google Scholar
  41. Unger J (2013) Rational use of GLP1 receptor agonists in patients with type 1 diabetes. Curr Diab Rep 13:663–668Google Scholar
  42. Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Hospital for Children and Adolescents, University of LeipzigLeipzigGermany

Personalised recommendations