Type 1 Diabetes in Children and Adolescents

Abstract

Key Messages•Suspicion of diabetes in a child should lead to immediate confirmation of the diagnosis and initiation of treatment to reduce the likelihood of diabetic ketoacidosis (DKA).•Management of pediatric DKA differs from DKA in adults because of the increased risk for cerebral edema. Pediatric protocols should be used.•Children should be referred for diabetes education, ongoing care and psychosocial support to a diabetes team with pediatric expertise.Note: Unless otherwise specified, the term “child” or “children” is used for individuals 0 to 18 years of age, and the term “adolescent” for those 13 to 18 years of age. •Suspicion of diabetes in a child should lead to immediate confirmation of the diagnosis and initiation of treatment to reduce the likelihood of diabetic ketoacidosis (DKA).•Management of pediatric DKA differs from DKA in adults because of the increased risk for cerebral edema. Pediatric protocols should be used.•Children should be referred for diabetes education, ongoing care and psychosocial support to a diabetes team with pediatric expertise.Note: Unless otherwise specified, the term “child” or “children” is used for individuals 0 to 18 years of age, and the term “adolescent” for those 13 to 18 years of age. Diabetes mellitus is the most common endocrine disease and one of the most common chronic conditions in children. Type 2 diabetes and other types of diabetes, including genetic defects of beta cell function, such as maturity-onset diabetes of the young, are being increasingly recognized in children and should be considered when clinical presentation is atypical for type 1 diabetes. This section addresses those areas of type 1 diabetes management that are specific to children. Children with new-onset type 1 diabetes and their families require intensive diabetes education by an interdisciplinary pediatric diabetes healthcare (DHC) team to provide them with the necessary skills and knowledge to manage this disease. The complex physical, developmental and emotional needs of children and their families necessitate specialized care to ensure the best long-term outcomes (1Glasgow A.M. Weissberg-Benchell J. Tynan W.D. et al.Readmissions of children with diabetes mellitus to a children's hospital.Pediatrics. 1991; 88: 98-104PubMed Google Scholar, 2von S.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: 122-127Crossref PubMed Scopus (30) Google Scholar). Education topics must include insulin action and administration, dosage adjustment, blood glucose (BG) and ketone testing, sick-day management and prevention of diabetic ketoacidosis (DKA), nutrition therapy, exercise, and prevention, detection, and treatment of hypoglycemia. Anticipatory guidance and lifestyle counselling should be part of routine care, especially during critical developmental transitions (e.g. upon school entry, beginning high school). Healthcare providers should regularly initiate discussions with children and their families about school, diabetes camp, psychological issues, substance use, obtaining a driver's license and career choices. Children with new-onset diabetes who present with DKA require a short period of hospitalization to stabilize the associated metabolic derangements and to initiate insulin therapy. Outpatient education for children with new-onset diabetes has been shown to be less expensive than inpatient education and associated with similar or slightly better outcomes when appropriate resources are available (3Clar C. Waugh N. Thomas S. Routine hospital admission versus out-patient or home care in children at diagnosis of type 1 diabetes mellitus.Cochrane Database Syst Rev. 2006; 2: CD004099Google Scholar). As improved metabolic control reduces both the onset and progression of diabetes-related complications in adults and adolescents with type 1 diabetes (4The Diabetes Control and Complications Trial Research Group. Effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med. 1993; 329: 977-986Crossref PubMed Scopus (0) Google Scholar, 5The Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial.J Pediatr. 1994; 125: 177-188Abstract Full Text Full Text PDF PubMed Scopus (955) Google Scholar), aggressive attempts should be made to reach the recommended glycemic targets outlined in Table 1. However, clinical judgement is required to determine which children can reasonably and safely achieve these targets. Treatment goals and strategies must be tailored to each child, with consideration given to individual risk factors. Young age at diabetes onset (<7 years of age) has been associated with poorer cognitive function in many studies (6Gaudieri P.A. Chen R. Greer T.F. Holmes C.S. Cognitive function in children with type 1 diabetes: a meta-analysis.Diabetes Care. 2008; 31: 1892-1897Crossref PubMed Scopus (57) Google Scholar). Episodes of severe hypoglycemia have been associated with poorer cognitive function in some follow-up studies, while other studies have found chronic hyperglycemia in young children to be associated with poorer cognitive performance (7Schoenle E.J. Schoenle D. Molinari L. et al.Impaired intellectual development in children with Type I diabetes: association with HbA(1c), age at diagnosis and sex.Diabetologia. 2002; 45: 108-114Crossref PubMed Scopus (118) Google Scholar, 8Ferguson S.C. Blane A. Wardlaw J. et al.Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function.Diabetes Care. 2005; 28: 1431-1437Crossref PubMed Scopus (87) Google Scholar, 9Strudwick S.K. Carne C. Gardiner J. et al.Cognitive functioning in children with early onset type 1 diabetes and severe hypoglycemia.J Pediatr. 2005; 147: 680-685Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 10Asvold B.O. Sand T. Hestad K. Bjorgaas M.R. Cognitive function in type 1 diabetic adults with early exposure to severe hypoglycemia: a 16-year follow-up study.Diabetes Care. 2010 Sep; 33: 1945-1947Crossref PubMed Scopus (23) Google Scholar). Analysis from a large multicentre observational study found that knowledge of glycemic targets by patients and parents, and consistent target setting by the diabetes team, was associated with improved metabolic control (11Swift P.G. Skinner T.C. de Beaufort C.E. et al.Hvidoere Study Group on Childhood DiabetesTarget setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.Pediatr Diabetes. 2010; 11: 271-278Crossref PubMed Scopus (27) Google Scholar).Table 1Recommended glycemic targets for children and adolescents with type 1 diabetesAge (years)A1C (%)Fasting/preprandial PG (mmol/L)Two-hour postprandial PG∗Postprandial monitoring is rarely done in young children except for those on pump therapy for whom targets are not available. (mmol/L)Considerations<6<8.06.0–10.0—Caution is required to minimize hypoglycemia because of the potential association between severe hypoglycemia and later cognitive impairment. Consider target of <8.5% if excessive hypoglycemia occurs6–12≤7.54.0–10.0—Targets should be graduated to the child's age. Consider target of <8.0% if excessive hypoglycemia occurs.13–18≤7.04.0–7.05.0–10.0Appropriate for most adolescents.†In adolescents in whom it can be safely achieved, consider aiming toward normal PG range (i.e. A1C ≤6.0%, fasting/preprandial PG 4.0–6.0 mmol/L and 2-hour postprandial PG 5.0–8.0 mmol/L).A1C, glycated hemoglobin; PG, plasma glucose.∗ Postprandial monitoring is rarely done in young children except for those on pump therapy for whom targets are not available.† In adolescents in whom it can be safely achieved, consider aiming toward normal PG range (i.e. A1C ≤6.0%, fasting/preprandial PG 4.0–6.0 mmol/L and 2-hour postprandial PG 5.0–8.0 mmol/L). Open table in a new tab A1C, glycated hemoglobin; PG, plasma glucose. 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. 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. Regardless of the insulin regimen used, all children should be treated to meet glycemic targets. The honeymoon period, which can last up to 2 years after diagnosis, is characterized by good glycemic control and low insulin requirements (<0.5 units/kg/day). At the end of this period, more intensive management may be required to continue meeting glycemic targets. Two methods of intensive diabetes management have been used: basal-bolus regimens (long-acting basal insulin analogues and rapid-acting bolus insulin analogues) and continuous subcutaneous insulin infusion (CSII; insulin pump therapy). Basal-bolus therapy has resulted in improved control over traditional twice daily NPH and rapid-acting bolus analogue therapy in some but not all studies (12Robertson K.J. Schoenle E. Gucev Z. et al.Insulin detemir compared with NPH insulin in children and adolescents with Type 1 diabetes.Diabet Med. 2007; 24: 27-34Crossref PubMed Scopus (88) Google Scholar, 13Chase H.P. Arslanian S. White N.H. Tamborlane W.V. 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: 547-553Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar). CSII is safe and effective and can be initiated at any age (14Phillip M. Battelino T. Rodriguez H. et al.Use of insulin pump therapy in the pediatric age-group. Consensus statement from the European Society for Paediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes, endorsed by the American Diabetes Association and the European Association for the Study of Diabetes.Diabetes Care. 2007; 30: 1653-1662Crossref PubMed Scopus (122) Google Scholar). A Cochrane review found that CSII gave slightly improved metabolic control over basal-bolus therapy (15Misso M.L. Egberts K.J. Page M. et al.Subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus.Cochrane Database Syst Rev. 2010; 1: CD005103PubMed Google Scholar). Some clinic-based studies of CSII in school-aged children and adolescents have shown a significant reduction in glycated hemoglobin (A1C) with reduced hypoglycemia 12 to 24 months after initiation of CSII when compared to pre-CSII levels (16Weinzimer S.A. Sikes K.A. Steffen A.T. et al.Insulin pump treatment of childhood type 1 diabetes.Pediatr Clin North Am. 2005; 52: 1677-1688Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). CSII, with use of a continuous glucose sensor, resulted in improved control over basal-bolus therapy alone (17Bergenstal R.M. Tamborlane W.V. Ahmann A. et al.Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes.N Engl J Med. 2010; 363: 311-320Crossref PubMed Scopus (228) Google Scholar). Most, but not all, pediatric studies of the long-acting basal insulin analogues, detemir and glargine, have demonstrated improved fasting BG levels and fewer episodes of nocturnal hypoglycemia with a reduction in A1C (12Robertson K.J. Schoenle E. Gucev Z. et al.Insulin detemir compared with NPH insulin in children and adolescents with Type 1 diabetes.Diabet Med. 2007; 24: 27-34Crossref PubMed Scopus (88) Google Scholar, 18Alemzadeh R. Berhe T. Wyatt D.T. 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: 1320-1324Crossref PubMed Scopus (57) Google Scholar, 19Murphy N.P. Keane S.M. Ong K.K. et al.Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens.Diabetes Care. 2003; 26: 799-804Crossref PubMed Scopus (132) Google Scholar, 20Hassan K. Rodriguez L.M. Johnson S.E. et al.A randomized, controlled trial comparing twice-a-day insulin glargine mixed with rapid-acting insulin analogs versus standard neutral protamine Hagedorn (NPH) therapy in newly diagnosed type 1 diabetes.Pediatrics. 2008; 121: e466-e472Crossref PubMed Scopus (24) Google Scholar, 21de Beaufort C.E. Swift P.G. Skinner C.T. et al.Hvidoere Study Group on Childhood Diabetes 2005Continuing stability of center differences in pediatric diabetes care: do advances in diabetes treatment improve outcome?.Diabetes Care. 2007; 30: 2245-2250Crossref PubMed Scopus (94) Google Scholar). Two large population-based observational studies have not found improved A1C in patients using basal-bolus therapy or CSII when compared to those using NPH and rapid-acting bolus analogues (21de Beaufort C.E. Swift P.G. Skinner C.T. et al.Hvidoere Study Group on Childhood Diabetes 2005Continuing stability of center differences in pediatric diabetes care: do advances in diabetes treatment improve outcome?.Diabetes Care. 2007; 30: 2245-2250Crossref PubMed Scopus (94) Google Scholar, 22Rosenbauer J Dost A Karges B et al.the DPV Initiative and the German BMBF Competence Network Diabetes MellitusImproved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria.Diabetes Care. 2012; 35: 80-86Crossref PubMed Scopus (26) Google Scholar). Individualization of insulin therapy to reach A1C targets, minimize hypoglycemia and optimize quality of life is indicated. Self-monitoring of BG is an essential part of management of type 1 diabetes (23Nordly S. Mortensen H.B. Andreasen A.H. et al.Factors associated with glycaemic outcome of childhood diabetes care in Denmark.Diabet Med. 2005; 22: 1566-1573Crossref PubMed Scopus (15) Google Scholar). Subcutaneous continuous glucose sensors allow detection of asymptomatic hypoglycemia and hyperglycemia. Use has resulted in improved diabetes control with less hypoglycemia in some studies. A randomized controlled trial did not show improved control in children and adolescents but did in adults (24Tamborlane W.V. Beck R.W. Bode B.W. et al.Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study GroupContinuous glucose monitoring and intensive treatment of type 1 diabetes.N Engl J Med. 2008; 359: 1464-1476Crossref PubMed Scopus (464) Google Scholar). Benefit correlated with duration of sensor use, which was much lower in children and adolescents. All children with type 1 diabetes should receive counselling from a registered dietitian experienced in pediatric diabetes. Children with diabetes should follow a healthy diet as recommended for children without diabetes in Eating Well with Canada's Food Guide (25Health CanadaEating Well with Canada's Food Guide. Health Canada, Health Products and Food Branch, Office of Nutrition Policy and Promotion, Ottawa, ON2007Google Scholar). This involves consuming a variety of foods from the 4 food groups (grain products, vegetables and fruits, milk and alternatives, and meat and alternatives). There is no evidence that 1 form of nutrition therapy is superior to another in attaining age-appropriate glycemic targets. Appropriate matching of insulin to carbohydrate content may allow increased flexibility and improved glycemic control (26Patton S.R. Dolan L.M. Powers S.W. Dietary adherence and associated glycemic control in families of young children with type 1 diabetes.J Am Diet Assoc. 2007; 107: 46-52Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 27Mehta S.N. Quinn N. Volkening L.K. Laffel L.M.B. Impact of carbohydrate counting on glycemic control in children with type 1 diabetes.Diabetes Care. 2009; 32: 1014-1016Crossref PubMed Scopus (30) Google Scholar), but the use of insulin to carbohydrate ratios is not required. The effect of protein and fat on glucose absorption must also be considered. Nutrition therapy should be individualized (based on the child's nutritional needs, eating habits, lifestyle, ability and interest) and must ensure normal growth and development without compromising glycemic control. This plan should be evaluated regularly and at least annually. Features suggestive of eating disorders and of celiac disease should be systematically sought out (28Markowitz J.T. Butler D.A. Volkening L.K. et al.Brief screening tool for disordered eating in diabetes internal consistency and external validity in a contemporary sample of pediatric patients with type 1 diabetes.Diabetes Care. 2010; 33: 495-500Crossref PubMed Scopus (22) Google Scholar). Hypoglycemia is a major obstacle for children with type 1 diabetes and can affect their ability to achieve glycemic targets. Children with early-onset diabetes are at greatest risk for disruption of cognitive function and neuropsychological skills, but the respective roles of hypoglycemia and hyperglycemia in their development are still questioned (6Gaudieri P.A. Chen R. Greer T.F. Holmes C.S. Cognitive function in children with type 1 diabetes: a meta-analysis.Diabetes Care. 2008; 31: 1892-1897Crossref PubMed Scopus (57) Google Scholar, 29Naguib J.M. Kulinskaya E. Lomax C.L. Garralda M.E. Neuro-cognitive performance in children with type 1 diabetes: a meta-analysis.J Pediatr Psychol. 2009; 34: 271-282Crossref PubMed Scopus (35) Google Scholar). Significant risk of hypoglycemia often necessitates less stringent glycemic goals, particularly for younger children. There is no evidence in children that 1 insulin regimen or mode of administration is superior to another for resolving nonsevere hypoglycemia. As such, treatment must be individualized (30Garg S. Moser E. Dain M.P. Rodionova A. Clinical experience with insulin glargine in type 1 diabetes.Diabetes Technol Ther. 2010; 12: 835-846Crossref PubMed Scopus (12) Google Scholar). Frequent use of continuous glucose monitoring in a clinical care setting may reduce episodes of hypoglycemia (31Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study GroupEffectiveness of continuous glucose monitoring in a clinical care environment. Evidence from the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring (JDRF-CGM) trial.Diabetes Care. 2010; 33: 17-22Crossref PubMed Scopus (50) Google Scholar). Severe hypoglycemia should be treated with pediatric doses of intravenous (IV) dextrose in the hospital setting or glucagon in the home setting. In children, the use of mini-doses of glucagon has been shown to be useful in the home management of mild or impending hypoglycemia associated with inability or refusal to take oral carbohydrate. A dose of 10 μg per year of age (minimum dose 20 μg, maximum dose 150 μg) is effective at treating and preventing hypoglycemia, with an additional doubled dose given if the BG has not increased in 20 minutes (32Hartley M. Thomsett M.J. Cotterill A.M. Mini-dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: the Brisbane experience.J Paediatr Child Health. 2006; 42: 108-111Crossref PubMed Scopus (12) Google Scholar, 33Haymond M.W. Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes.Diabetes Care. 2001; 24: 643-645Crossref PubMed Google Scholar). See Table 2 for treatment of mild-to-moderate hypoglycemia.Table 2Examples of carbohydrate for treatment of mild-to-moderate hypoglycemiaPatient weight<15 kg15–30 kg>30 kgAmount of carbohydrate5 g10 g15 gCarbohydrate source Glucose tablet (4 g)12 or 34 Dextrose tablet (3 g)235 Apple or orange juice, regular soft drink, sweet beverage (cocktails)40 mL85 mL125 mL Open table in a new tab Diabetes control may worsen during adolescence. Factors responsible for this deterioration include adolescent adjustment issues, psychosocial distress, intentional insulin omission and physiological insulin resistance. A careful multidisciplinary assessment should be undertaken for every child with chronic poor metabolic control (e.g. A1C >10.0%) to identify potential causative factors, such as depression and eating disorders, and to identify and address barriers to improved control. Multipronged interventions that target emotional, family and coping issues show a modest reduction in A1C with reduced rates of hospital admission (34Winkley K. Ismail K. Landau S. et al.Psychological interventions to improve glycaemic control in patients with type 1 diabetes: systematic review and meta-analysis of randomised controlled trials.BMJ. 2006; 333: 65Crossref PubMed Scopus (114) Google Scholar, 35Hood K.K. Rohan J.M. Peterson C.M. Drotar D. Interventions with adherence-promoting components in pediatric type 1 diabetes: meta-analysis of their impact on glycemic control.Diabetes Care. 2010; 33: 1658-1664Crossref PubMed Scopus (21) Google Scholar). DKA occurs in 15% to 67% of children with new-onset diabetes and at a frequency of 1 to 10 episodes per 100 patient years in those with established diabetes (36Levy-Marchal C. Patterson C.C. Green A. Geographic variation of presentation at diagnosis of type 1 diabetes in children: the EURODIAB study.Diabetologia. 2001; 44: B75-B80Crossref PubMed Google Scholar). As DKA is the leading cause of morbidity and mortality in children with diabetes, strategies are required to prevent the development of DKA (37Patterson C.C. Dahlquist G. Harjutsalo V. et al.Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989.Diabetologia. 2007; 50: 2439-2442Crossref PubMed Scopus (43) Google Scholar). In new-onset diabetes, DKA can be prevented through earlier recognition and initiation of insulin therapy. Public awareness campaigns about the early signs of diabetes have significantly reduced the frequency of DKA in new-onset diabetes (38Vanelli M. Chiari G. Ghizzoni L. et al.Effectiveness of a prevention program for diabetic ketoacidosis in children: an 8-year study in schools and private practices.Diabetes Care. 1999; 22: 7-9Crossref PubMed Scopus (132) Google Scholar). In children with established diabetes, DKA results from failing to take insulin or poor sick-day management. Risk is increased in children with poor metabolic control or previous episodes of DKA, peripubertal and adolescent girls, children on insulin pumps or long-acting basal insulin analogues, children with psychiatric disorders and those with difficult family circumstances (39Keenan H.T. Foster C.M. Bratton S.L. Social factors associated with prolonged hospitalization among diabetic children.Pediatrics. 2002; 109: 40-44Crossref PubMed Scopus (33) Google Scholar, 40Hanas R. Lindgren F. Lindblad B. A 2-yr national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use.Pediatr Diabetes. 2009; 10: 33-37Crossref PubMed Scopus (22) Google Scholar, 41Karges B. Kapellen T. Neu A. et al.Diabetes Prospective Documentation DPV InitiativeGerman Federal Ministry for Education and Research BMBF Competence Network of Diabetes MellitusLong-acting insulin analogs and the risk of diabetic ketoacidosis in children and adolescents with type 1 diabetes: a prospective study of 10,682 patients from 271 institutions.Diabetes Care. 2010; 33: 1031-1033Crossref PubMed Scopus (10) Google Scholar). The frequency of DKA in established diabetes can be decreased with education, behavioural intervention and family support (42Drozda D.J. Dawson V.A. Long D.J. et al.Assessment of the effect of a comprehensive diabetes management program on hospital admission rates of children with diabetes mellitus.Diabetes Educ. 1990; 16: 389-393Crossref PubMed Google Scholar, 43Ellis D. Naar-King S. Templin T. et al.Multisystemic therapy for adolescents with poorly controlled type 1 diabetes: reduced diabetic ketoacidosis admissions and related costs over 24 months.Diabetes Care. 2008; 31: 1746-1767Crossref PubMed Scopus (26) Google Scholar), as well as access to 24-hour telephone services for parents of children with diabetes (44Hoffman W.H. O'Neill P. Khoury C. et al.Service and education for the insulin-dependent child.Diabetes Care. 1978; 1: 285-288Crossref PubMed Google Scholar, 45Chiari G. Ghidini B. Vanelli M. Effectiveness of a toll-free telephone hotline for children and adolescents with type 1 diabetes. A 5-year study.Acta Biomed. 2003; 74: 45-48PubMed Google Scholar). While most cases of DKA are corrected without event, 0.7% to 3.0% of pediatric cases are complicated by cerebral edema (CE) (46Edge J.A. Hawkins M.M. Winter D.L. et al.The risk and outcome of cerebral oedema developing during diabetic ketoacidosis.Arch Dis Child. 2001; 85: 16-22Crossref PubMed Google Scholar), which is associated with significant morbidity (21% to 35%) and mortality (21% to 24%) (47Rosenbloom A.L. Intracerebral crises during treatment of diabetic ketoacidosis.Diabetes Care. 1990; 13: 22-33Crossref PubMed Google Scholar). In contrast, CE has rarely been reported in adults (39Keenan H.T. Foster C.M. Bratton S.L. Social factors associated with prolonged hospitalization among diabetic children.Pediatrics. 2002; 109: 40-44Crossref PubMed Scopus (33) Google Scholar, 47Rosenbloom A.L. Intracerebral crises during treatment of diabetic ketoacidosis.Diabetes Care. 1990; 13: 22-33Crossref PubMed Google Scholar). Although the cause of CE is still unknown, several factors are associated with increased risk (Table 3) (48Glaser N. Barnett P. McCaslin I. et al.Risk factors for cerebral edema in children with diabetic ketoacidosis.N Engl J Med. 2001; 344: 264-269Crossref PubMed Scopus (324) Google Scholar, 49Harris G.D. Fiordalisi I. Harris W.L. et al.Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study.J Pediatr. 1990; 117: 22-31Abstract Full Text PDF PubMed Scopus (104) Google Scholar, 50Harris G.D. Fiordalisi I. Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in 231 episodes.Arch Pediatr Adolesc Med. 1994; 148: 1046-1052Crossref PubMed Google Scholar, 51Hale P.M. Rezvani I. Braunstein A.W. et al.Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes.Acta Paediatr. 1997; 86: 626-631Crossref PubMed Google Scholar, 52Edge J.A. Jakes R.W. Roy Y. et al.The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children.Diabetologia. 2006; 49: 2002-2009Crossref PubMed Scopus (72) Google Scholar). A bolus of insulin prior to infusion is not recommended since it does not offer faster resolution of acidosis (53Fort P. Waters S.M. Lifshitz F. Low-dose insulin infusion in the treatment of diabetic ketoacidosis: bolus versus no bolus.J Pediatr. 1980; 96: 36-40Abstract Full Text PDF PubMed Google Scholar, 54Lindsay R. Bolte R.G. The use of an insulin bolus in low-dose insulin infusion for pediatric diabetic ketoacidosis.Pediatr Emerg Care. 1989; 5: 77-79Crossref PubMed Google Scholar) and may contribute to CE (55Hoorn E.J. Carlotti A.P. Costa L.A. et al.Preventing a drop in effective plasma osmolality to minimize the likelihood of cerebral edema during treatment of children with diabetic ketoacidosis.J Pediatr. 2007; 150: 467-473Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar). Recent evidence suggests early insulin administration (within the first hour of fluid replacement) may increase the risk for CE (52Edge J.A. Jakes R.W. Roy Y. et al.The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children.Diabetologia. 2006; 49: 2002-2009Crossref PubMed Scopus (72) Google Scholar). Special caution should be exercised in young children with DKA and new-onset diabetes or a greater degree of acidosis and extracellular fluid volume depletion because of the increased risk of CE. Use of bedside criteria may allow earlier identification of patients who require treatment for CE (56Muir A.B. Quisling R.G. Yang M.C. et al.Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification.Diabetes Care. 2004; 27: 1541-1546Crossref PubMed Scopus (62) Google Scholar). DKA should be managed according to published protocols for management of pediatric DKA (Figure 1) (57Wolfsdorf J. Craig M.E. Daneman D. et al.International Society for Pediatric and Adolescent DiabetesDiabetic ketoacidosis.Pediatr Diabetes. 2007; 8: 28-43Crossref PubMed Scopus (76) Google Scholar).Table 3Risk factors for cerebral edema•Younger age (<5 years)•New-onset diabetes•High initial serum urea•Low initial partial pressure of arterial carbon dioxide (pCO2)•Rapid administration of hypotonic fluids•IV bolus of insulin•Early IV insulin infusion (within first hour of administration of fluids)•Failure of serum sodium to rise during treatment•Use of bicarbonateIV, intravenous. Open table in a new tab IV, intravenous. Historically, national guidelines have recommended influenza and pneumococcal immunization for children with type 1 diabetes (58National Advisory Committee on Immunization Canadian Immunization Guide.7th ed. Public Health Agency of Canada, Ottawa, ON2006Google Scholar, 59Infectious Diseases and Immunization Committee Canadian Paediatric SocietyPneumococcal vaccine for children.Paediatr Child Health. 2002; 6: 214-2