Effectively Managing Type 1 Diabetes in Children – Education and Optimising New Technology

Thomas Danne, Olga Kordonouri
European Endocrinology, 2008;4(1):14-8
pdf icon download pdf Printer icon matthew [dot] goodwin [at] toucmedicalinformation [dot] com (subject: Reprint%20Request, amp, body: %20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Dear%20Matthew%2C%0A%0AI%20would%20like%20to%20request%20a%20quote%20for%20.........%20reprints%20of%20the%20following%20article%3A%0A%0Ahttp%3A%2F%2Fwww.touchendocrinology.com%2F%2Farticles%2Feffectively-managing-type-1-diabetes-children-education-and-optimising-new-technology%0A%0APlease%20contact%20me%20on%20the%20following%20details.%0A%0A.........%0A%0AKind%20regards%2C%0A%0A.........%0A) (Order reprints)

Paradigm Shift in Paediatric Diabetes Treatment

There has been a recent paradigm shift in the treatment of paediatric diabetes. Previously, it was thought that the best way to overcome barriers to treating children would be to spare them from an insulin regimen consisting of many daily injections. Consequently, treatment consisted of two daily injections of pre-mixed insulins. This was accompanied by the need to follow a strict diet and daily schedule in order to match the insulin intake. Indeed, some centres are reporting good results with this approach.16 However, the majority of paediatric diabetologists now believe that the gold standard treatment for children with diabetes is intensified insulin therapy. Intensified insulin therapy aims to mimic as closely as possible the physiological insulin profile observed in non-diabetic individuals. This kind of regimen is also believed to allow the flexibility required with the lifestyle needs of children with diabetes. To match these challenges, the choice of rapid-, short-, intermediate- and long-acting insulins and insulin analogues (see Figure 2), as well as devices such as insulin pumps and glucose sensors, have led to many recent new developments in the treatment options for children with diabetes.

Insulin Pump Therapy for Children

Over the last decade, continuous subcutaneous insulin infusion (CSII) has increased in popularity among paediatric patients with diabetes. Theoretically, CSII offers the most physiological method of insulin delivery due to its ability to more closely simulate the normal pattern of insulin secretion, namely continuous 24-hour adjustable ‘basal’ delivery of insulin superimposed with prandial-related ‘boluses’. In addition, CSII offers more flexibility and more precise insulin delivery than multiple daily injections (MDIs). Although randomised, controlled trials in young children have not yielded the same beneficial effects as the nonrandomised paired comparison studies, it is incorrect to conclude that paediatric pump therapy offers no real advantages to MDIs.17,18 The results of the large European Pedpump data collection indicate the safety of pumps for all age groups and document the flexibility of CSII, with many children taking seven or more daily prandial or correction boluses.19,20 The low rate of hypoglycaemia makes pumps an attractive choice, particularly for pre-school children.21 Poor motivation and support leading to a low number of boluses or not following the rules for preventing diabetic ketoacidosis (DKA) in CSII may lead to adverse outcomes. This may be a caveat to prescribing CSII,17 and it highlights the importance of individualising the decision as to the modality of therapy according to developmental stage and tasks.

Insulin Analogues

Insulin analogues are safe for use in paediatric patients. As pre-prandial insulin treatment is often problematic in young children with unpredictable and irregular eating habits, the post-prandial injection of rapid-acting insulin analogues offers the ease of adjusting the administration time and dosage according to mealtime and the size of the meal in injection therapy and CSII. In accordance with the pharmacokinetic results obtained in adults, insulin aspart and insulin glulisine were rapidly absorbed and eliminated in paediatric patients also.22,23 Post-prandial administration of insulin aspart was shown to be a safe and effective alternative to pre-prandial administration in a study of 76 children and adolescents,24 as well as in a trial of pre-school children two to six years of age.25 Insulin suspensions with protamine (NPH) or zinc have been used for several years for delaying insulin action for basal insulin substitution. In most countries, the two basal analogues – insulin glargine and detemir – have not been formally approved for children below six years of age. However, there are reports of successful use of glargine in children from under one to five years of age.26 Randomised and observational studies with insulin glargine as the basal insulin have also shown reductions in nocturnal hypoglycaemia.27,28 In a six-month multicentre trial, 347 children (aged six to 17 years) with type 1 diabetes received comparable doses of insulin detemir or NPH insulin plus pre-meal insulin aspart.29 At followup, mean HbA1c decreased by approximately 0.8% to 8% in both treatment groups, but children in the insulin detemir group had a significant 26% reduction in nocturnal hypoglycaemia compared with NPH insulin. In another cross-over study of 68 adolescents comparing the bedtime injection of semilente zinc–insulin with insulin detemir, both insulins were equally effective in terms of the fasting plasma glucose levels. Despite an average 1.7-fold higher insulin dose to achieve the fasting blood glucose target, the incidence of mild and severe night-time hypoglycaemia was lower with detemir.30 Compared with NPH, insulin detemir is also associated with less weight gain or weight reduction in paediatric patients29 and less variability.31

References:
  1. The DCCT Research Group, The effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial, J Pediatr, 1994;125(2):177–88.
  2. DCCT/EDIC Research Group, Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial, J Pediatr, 2001;139(6):804–12.
  3. Danne T, Weber B, Hartmann R, et al., Long-term glycemic control has a nonlinear association to the frequency of background retinopathy in adolescents with diabetes. Followup of the Berlin Retinopathy Study, Diabetes Care, 1994;17: 1390–96.
  4. Hanas R, Donaghue K, Klingensmith G, Swift PG, International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines 2006–2007, Pediatr Diabetes, 2006;7(6):341–2.
  5. National Institute for Clinical Excellence, Type 1 diabetes: diagnosis and management of type 1 diabetes in children, young people and adults, 2004. Available at: www.nice.org.uk/pdf/CG015NICEguideline.pdf
  6. The DCCT Research Group, The effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial, J Pediatr, 1994;125:177–88.
  7. DCCT/EDIC Research Group, Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial, J Pediatr, 2001;139:804–12.
  8. The Diabetes Research in Children Network (DirecNet) Study Group, The relationship of A1c to glucose concentrations in children with type 1 diabetes: Assessments by high frequency glucose determinations by sensors, Diabetes Care, 2007; Epub ahead of print.
  9. Heller S, Kim H, Draeger E, Within-person variation in fasting blood glucose is correlated to incidence of hypoglycemia in people with type 1 diabetes treated with insulin detemir and NPH insulin, Diabetologia, 2004;47(Suppl. 1):A303.
  10. Service FJ, Molnar GD, Rosevear JW, et al., Mean Amplitude of Glycemic Excursions, a Measure of Diabetic Instability, Diabetes, 1970;19:644–55.
  11. Saudek CD, Derr RL, Kalyani RR, Assessing glycemia in diabetes using self-monitoring blood glucose and haemoglobin A1c, JAMA, 2006;295:1688–97.
  12. Danne T, Lange K, Kordonouri O, New developments in the treatment of type 1 diabetes in children, Arch Dis Child, 2007;92:1015–19.
  13. Brownlee M, Hirsch IB, Glycemic variability: a hemoglobin A1cindependent risk factor for diabetic complications, JAMA, 2006; 295:1707–8.
  14. Alemzadeh R, Loppnow C, Parton E, Kirby M, Glucose sensor evaluation of glycemic instability in pediatric type 1 diabetes mellitus, Diabetes Technol Ther, 2003;5:167–73.
  15. Ryan EA, Shandro T, Green K, et al., Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation, Diabetes, 2004;53:955–62.
  16. Dorchy H, Dietary management for children and adolescents with diabetes mellitus: personal experience and recommendations, J Pediatr Endocrinol Metab, 2003;16: 131–48.
  17. Phillip M, Battelino T, Rodriguez H, et al., Consensus Statement on the Use of Insulin Pump Therapy in the Pediatric Age-Group, Diabetes Care, 2007;30(6):1653–62.
  18. Nimri R, Weintrob N, Benzaquen H, et al., Insulin pump therapy in youth with type 1 diabetes: a retrospective paired study, Pediatrics, 2006;117(6):2126–31.
  19. Danne T, Battelino T, Kordonouri O, et al., A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries, Pediatr Diabetes, 2005;6(4):193–8.
  20. Danne T, Battelino T, Jarosz-Chobot P, et al., for the PedPumpStudy Group, Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescent with type 1 diabetes: experience from the PedPump Study in 17 countries, Diabetologia, 2008; in press.
  21. Weinzimer SA, Ahern JH, Doyle EA, et al., Persistence of benefits of continuous subcutaneous insulin infusion in very young children with type 1 diabetes: a follow-up report, Pediatrics, 2004;114(6):1601–5.
  22. Mortensen H, Lindholm A, Olsen B, Hylleberg B, Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes, Eur J Pediatric, 2000;159:483–8.
  23. Danne T, Becker RH, Heise T, et al., Pharmacokinetics, prandial glucose control, and safety of insulin glulisine in children and adolescents with type 1 diabetes, Diabetes Care, 2005;(9): 2100–2105.
  24. Danne T, Aman J, Schober E, et al., A comparison of postprandial and pre-prandial administration of insulin aspart in children and adolescents with type 1 diabetes, Diabetes Care, 2003;26:2359–84.
  25. Danne T, Råstam J, Odendahl R, et al., Parental preference of Prandial Insulin Aspart compared to Preprandial Human Insulin in a Basal-bolus Scheme with NPH insulin in a Twelve Week Crossover-Study of Preschool Children with Type 1 Diabetes, Pediatr Diabetes, 2007;8:278–85.
  26. Alemzadeh R, Berhe T, Wyatt DT, Flexible insulin therapy with glargine insulin improved glycemic control and reduced severe hypoglycemia among preschool-aged children with type 1 diabetes mellitus, Pediatrics, 2005;115(5):1320–24.
  27. Chase HP, Dixon B, Pearson J, et al., Reduced hypoglycemic episodes and improved glycemic control in children with type 1 diabetes using insulin glargine and neutral protamine Hagedorn insulin, J Pediatr, 2003;143(6):737–40.
  28. Schrober E, Schoenle E, Can Dyk J, et al., Comparative trial between insulin glargine and NPH insulin in children and adolescents with type 1 diabetes mellitus, J Pediatr Endocrinol Metab, 2002;15(4):369–76.
  29. Robertson K, Schönle E, Gucev Z, et al., Benefits of insulin detemir over NPH insulin in children and adolescents with type 1 diabetes: lower and more predictable fasting plasma glucose and lower risk of nocturnal hypoglycaemia, Diabet Med, 2005; 22(Suppl. 2):45 (abstract P66).
  30. Kordonouri O, Datz N, Hoeffe J, et al., Efficacy and Safety of Bedtime Insulin Detemir vs. Insulin Semilente in Children, Adolescents, and Young Adults with Type 1 Diabetes. A Randomised, Open-Label, Cross-Over Study, Pediatr Diabetes, 2006 ;7(Suppl. 5):68–9 (abstract).
  31. Danne T, Lupke K, Walte K, et al., Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes, Diabetes Care, 2003;26:3087–92.
  32. von Sengbusch S, Muller-Godeffroy E, Hager S, et al., Mobile diabetes education and care: intervention for children and young people with Type 1 diabetes in rural areas of northern Germany, Diabet Med, 2006;23:122–7.
  33. Skinner TC, John M, Hampson SE, Social support and personal models of diabetes as predictors of self-care and well-being: a longitudinal study of adolescents with diabetes, J Pediatric Psychology, 2000;25:257–67.
  34. Anderson B, Ho J, Brackett J, et al., Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus, J Pediatr, 1997;130:257–65.
  35. American Diabetes Association. Diabetes care in the school and day care setting (Position Statement), Diabetes Care, 2004;27 (Suppl. 1):S122–S128.
  36. Lange K, Danne T, Kordonouri O, et al., Diabetes in childhood: everyday burden and professional consequences for parents, Dtsch Med Wochenschr, 2004;129(20):1130–34.
  37. Svoren BM, Butler D, Levine BS, et al., Reducing acute adverse outcomes in youths with type 1 diabetes: a randomized, controlled trial, Pediatrics, 2003;112:914–22.
  38. Howells L, Wilson AC, Skinner TC, et al., A randomized control trial of the effect of negotiated telephone support on glycaemic control in young people with type 1 diabetes, Diabet Med, 2002;19:643–8.
  39. Gross TM, Bode BW, Einhorn D, et al., Performance evaluation of the MiniMed continuous glucose monitoring system during patient home use, Diabetes Technol Ther, 2000;2:49–56.
  40. Bode B, Gross K, Rikalo N, et al., Alarms based on real-time sensor glucose values alert patients to hypo- and hyperglycemia: the guardian continuous monitoring system, Diabetes Technol Ther, 2004;6:105–13.
  41. Feldman B, Brazg R, Schwartz S, Weinstein R, A continuous glucose sensor based on wired enzyme technology: results from a 3-day trial in patients with type 1 diabetes, Diabetes Technol Ther, 2003;5:769–79.
  42. Bailey TS, Zisser HC, Garg SK, Reduction in hemoglobin A1C with real-time continuous glucose monitoring: results from a 12-week observational study, Diabetes Technol Ther, 2007; 9:203–10.
  43. Weintrob N, Schechter A, Benzaquen H, et al., Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs. continuous subcutaneous insulin infusion, Arch Pediatr Adolesc Med, 2004;158:677–84.
  44. Gandrud LM, Xing D, Kollman C, et al., The Medtronic Minimed Gold continuous glucose monitoring system: an effective means to discover hypo- and hyperglycemia in children under 7 years of age, Diabetes Technol Ther, 2007;9:307–16.
  45. Golicki DT, Golicka D, Groele L, Pankowska E, Continuous Glucose Monitoring System in children with type 1 diabetes mellitus: asystematic review and meta-analysis, Diabetologia, 2008;51:233–40.
  46. Yates K, Hasnat Milton A, Dear K, Ambler G, Continuous glucose monitoring-guided insulin adjustment in children and adolescents on near-physiological insulin regimens: a randomized controlled trial, Diabetes Care, 2006;29:1512–17.
  47. Lagarde WH, Barrows FP, Davenport ML, et al., Continuous subcutaneous glucose monitoring in children with type 1 diabetes mellitus: a single-blind, randomized, controlled trial, Pediatr Diabetes, 2006;7:159–64.
  48. Deiss D, Hartmann R, Schmidt J, Kordonouri O, Results of an randomized controlled cross-over-trial on the effect of continuous glucose monitoring (CGMS) on glycemic control in childen and adolescents with type 1 diabetes, Exp Clin Endocrinol Diabetes, 2006;114:63–7.
  49. Ludvigsson J, Hanas R, Continuous subcutaneous glucose monoitoring improved metabolic control in pediatric patients with type 1 diabetes: a controlled cross-over study, Pediatrics, 2003;111:933–8.
  50. Chase HP, Kim LM, Owen SL, et al., Continuous glucose monitoring in children with type 1 diabetes, Pediatrics, 2001; 107:222–6
  51. Wiltshire EJ, Newton K, McTavish L, Unrecognised hypoglycaemia in children and adolescents with type 1 diabetes using the continuous glucose monitoring system: prevalence and contributors, J Paediatr Child Health, 2006;42:758–63.
  52. Deiss D, Kordonouri O, Hartmann R, et al., Treatment with insulin glargine reduces asymptomatic hypoglycemia detected by continuous subcutaneous glucose monitoring in children and adolescents with type 1 diabetes, Pediatr Diabetes, 2007;8: 157–62.
  53. McDonnell CM, Northam EA, Donath SM, Werther GA, Cameron FJ, Hyperglycemia and externalizing behavior in children with type 1 diabetes, Diabetes Care, 2007;30(9): 2211–15.
  54. Deiss D, Bolinder J, Riveline JP, et al., Improved glycemic control in poorly controlled patients with type 1 diabetes using real-time continuous glucose monitoring, Diabetes Care, 2006;29: 2730–32.
  55. Tubiana-Rufi N, Riveline JP, Dardari D, Real-time continuous glucose monitoring using Guardian®RT: from research to clinical practice, Diabetes Metab, 2007;33:415–20.
  56. Halvorson M, Carpenter S, Kaiserman K, Kaufman F, A pilot trial in pediatrics with the sensor-augmented pump: combining real-time continuous glucose monitoring with the insulin pump, J Pediatric, 2007;150:103–5.
  57. Wilson DM, Beck RW, Tamborlane WV, et al., The accuracy of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes, Diabetes Care, 2007;30:59–64.
  58. Buckingham B, Caswell K, Wilson DM, Real-time continuous glucose monitoring, Curr Opin Endocrinol Diabetes Obes, 2007; 14:288–95.
  59. Diabetes Research in Children Network (DirecNet) Study Group, Buckingham B, Beck RW, et al., Continuous glucose monitoring in children with type 1 diabetes, J Pediatr, 2007;151:388–93, 393.e1–2.
  60. Weinzimer S, Xing D, Tansey M, et al., Diabetes Research in Children Network (DirecNet) Study Group, FreeStyle NavigatorTM Continuous Glucose Monitoring System Use in Children with Type 1 Diabetes using glargine-based multiple daily dose regimens: Results of a Pilot Trial, Diabetes Care, 2008;31(3):525–7.
  61. Diabetes Research In Children Network (Direcnet) Study Group, Buckingham BA, Kollman C, et al., Evaluation of factors affecting CGMS calibration, Diabetes Technol Ther, 2006;8(3): 318–25.
  62. Diabetes Research in Children Network (DirecNet) Study Group, Psychological aspects of continuous glucose monitoring in pediatric type 1diabetes, Pediatr Diabetes, 2006;7(1):32–8.
  63. Buckingham B, Halvorson M, Kunselman E, Kaufmann FR, Sensor augmented pump therapy in adolescents: results of the first treat-to-target study, Diabetes, 2007;56(Suppl. 1):A479.
  64. Updike SJ, Shults MC, Gilligan BJ, Rhodes RK, A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration, Diabetes Care, 2000;23:208–14.
  65. Renard E, Implantable closed-loop glucose-sensing and insulin delivery: the future for insulin pump therapy, Curr Opin Pharmacol, 2002;2(6):708–16.
  66. Hovorka R, Chassin LJ, Wilinska ME, Closing the loop: The ADICOL experience, Diabetes Thechnol Ther, 2004;6(3):307–18.
  67. Dassau E, Bequette BW, Buckingham BA, Doyle FJ, Detection of a Meal Using Continuous Glucose Monitoring (CGM): Implications for an Artificial {beta}-cell, Diabetes Care, 2008; 31(2):295–300.
  68. Chase HP, Lockspeiser T, Peery B, et al., The impact of the diabetes control and complications trial and humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes, Diabetes Care, 2001;24:430–44.
  69. Danne T, Mortensen HB, Hougaard P, et al., For the Hvidore Study Group on Childhood Diabetes.Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group, Diabetes Care, 2001;24:1342–47.
  70. Danne T, von Schutz W, Lange K, et al., Current practice of insulin pump therapy in children and adolescents – the Hannover recipe, Pediatr Diabetes, 2006;7(Suppl. 4):25–31.
  71. Swift PGF, de Beaufort CE, Skinner TC, on behalf of the Hvidore Study Group Services provided by the diabetes team: do they effect the glycemic outcome?, Ped Diabetes, 2006;7 (Suppl. 5):19 (abstract).
  72. Klonoff DC, Continuous glucose monitoring: roadmap for 21st century diabetes therapy, Diabetes Care, 2005;28:1231–9.