Vivekenanda Pateda Department of Pediatric Endocrinology, University of Sam Ratulangi, Manado, Indonesia *E-mail: firstname.lastname@example.org
Diabetes mellitus is a disorder of the metabolic homeostasis controlled by insulin, resulting in abnormalities of carbohydrate and lipid metabolism. Type 1 diabetes (also called juvenile-onset diabetes mellitus and insulin-dependent diabetes mellitus) is caused by an absolute insulin deficiency, the result of a loss of the insulin-producing beta cells of the pancreas.1 Regular and life-long insulin administration is therefore necessary to prevent hyperglycemia, metabolic decompensation and life-threatening diabetic ketoacidosis (DKA).2 Insulin treatment that mimics normal physiological patterns as closely as possible remains the cardinal principle of treatment for type 1 diabetes (T1DM).3 Since the breakthrough discovery of insulin in 1921, insulin preparation methods and treatment strategies have advanced signifcantly.4 Although initial preparations of insulin from animal sources were successful in treating patients with diabetes, these early insulins have certain clinical limitations prompting researchers to the development of synthetic and recombinant ?human? insulins but hypoglycemia still persisted and still did not mimic natural insulin. This prompted the development of insulin analogs, rapid and long-acting.3-4 These insulins resulted in some improvement in the care of diabetes, but their beneficial extent in a long-term clinical setting is not fully established.3 Insulin therapy is the mainstay of medical management of type 1 diabetes. A variety of insulin regimens can be used, but few have been studied specifically in children with new-onset diabetes.5 Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM.6 The choice of insulin regimen depends on many factors, including the child?s age, duration of diabetes, family lifestyle, socioeconomic factors, and family, patient, and physician preferences.3,5 The majority of diabetic children require 0.5-1.0 units of insulin/kg/day.3 The obese or pubertal child typically requires more insulin, as both conditions exacerbate insulin resistance.7 Younger children, on the other hand, require reduced amounts of insulin because of lower body weight, higher insulin sensitivity, and the risk of hypoglycemia.6 The insulin dosage should be adapted on the basis of the daily pattern of blood glucose, through regular review and reassessment, and patient factors such as exercise, age,weight, inercurrent illness and pubertal status.3,6 Regardless of the insulin regimen used, all children should be treated to meet glycemic targets.5 Intensive regimens based on multiple daily injections (MDI) with differential substitution of basal and prandial insulin (basal bolus) have become the gold standard in pediatric diabetology.3 Basal-bolus therapy has resulted in improved control over traditional twice-daily neutral protamine Hagedorn (NPH) and rapid-acting bolus analogue therapy in some but not all studies.8-10 In this regimen, a long acting insulin is used to cover the glucose levels resulting from gluconeogenesis, which is administered primarily in a fixed dose. Separately, the prandial insulin is calculated according to carbohydrate counting being dosed flexibly according to the current glucose measurement and planned activity level.11 Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycemia.2 However, there is wide variation in insulin regimens. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental e?ects of hypoglycemia and hyperglycemia offer new opportunities and perspectives in T1DM management.2 In a meta-analysis of 12 randomised controlled trials (RCTs) comparing CSII versus MDI regimens, CSII was shown to reduce mean HbA1c by approximately 0.51% as well as BG variability and this was achieved by an average reduction of total insulin dose of 14%.12 The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy with MDI or CSII delivered by a multidisciplinary team improved glucose control and resulted in better long-term outcomes.13 Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation.6 The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose (SMBG) and/or a continuous glucose monitoring (CGM) system to avoid critical hypoglycemia and glucose variability.5 A recent Cochrane review demonstrated that CGM combined with MDI lowered HbA1c levels by 0.2 %, while those patients on insulin pump therapy augmented by CGM had, on average, a 0.7 % improvement in HbA1c levels across all age groups, compared with patients using MDI and SMBG.14 Insulin therapy should be individualized to reach HbA1C targets, minimize hypoglycemia and optimize quality of life with prevention of micro- and macrovascular complications.2-3,5
1. Cooke DW, Plotnick L. Type 1 Diabetes Mellitus in Pediatrics. Pediatric in Review Nov 2008, 29 (11) 374-385. 2. Iqbal A, Novodvorsky P, Heller SR. Recent updates on type 1 diabetes mellitus management for clinicians. Diabetes Metab J 2018;42:3-18. 3. Danne T, Phillip M, Buckingham BA, Jarosz-Chobot P, Saboo B, Urakami T, et Al. ISPAD Clinical Practice Consensus Guidelines 2018 : Insulin treatment in Children and adolescent with diabetes. Pediatr Diabetes. 2018 Oct;19 Suppl 27:115-135. 4. Tibaldi JM. Evolution of insulin development: focus on key parameters. Adv Ther (2012) 29(7):590?619. 5. Wherrett D, Huot C, Mitchell B, Pacaud D. Type 1 Diabetes in Children and Adolescents. Can J Diabetes 37 (2013) S153-S162. 6. Malik FS, Tap CE. Insulin Therapy in Children and Adolescents with Type 1 Diabetes. Paediatr Drugs. 2014 Apr;16(2):141-50. 7. Liu LL, Lawrence JM, Davis C, et al. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth Study. Pediatr Diabetes. 2010;11(1):4?11 8. Robertson KJ, Schoenle E, Gucev Z, et al. Insulin detemir compared with NPH insulin in children and adolescents with Type 1 diabetes. Diabet Med 2007;24:27?34. 9. Chase HP, Arslanian S, White NH, et al. Insulin glargine versus intermediate acting insulin as the basal component of multiple daily injection regimens for adolescents with type 1 diabetes mellitus. J Pediatr 2008;153:547?53. 10. Pihoker C, Badaru A, Anderson A, et al. Insulin regimens and clinical outcomes in a type 1 diabetes cohort: The SEARCH for Diabetes in Youth study. Diabetes Care 2013;36:27?33 11. Bister T, Kordonouri O, Danne T. Pharmacotherapy of type1 diabetes in children and adolescents: more than insulin?. Ther Adv Endocrinol Metab. 2018, Vol. 9(5) 157?166. 12. Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ 2002;324:705. 13. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Mortality in type 1 diabetes in the DCCT/EDIC versus the general population. Diabetes Care. 2016;39:1378-83. 14. Langendam M, Luijf YM, Hooft L, DeVries JH, Mudde AH, Scholten RJPM. Continuous glucose monitoring systems for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2012;(1): CD008101.