Type 2 Diabetes in Children and Adolescents

Abstract

Key Messages•Anticipatory guidance regarding healthy eating and active lifestyle is recommended to prevent obesity.•Regular targeted screening for type 2 diabetes is recommended in children at risk.•Children with type 2 diabetes should receive care in consultation with an interdisciplinary pediatric diabetes healthcare team.•Early screening, intervention and optimization of glycemic control are essential, as the onset of type 2 diabetes during childhood is associated with severe and early onset of microvascular complications.Note: Unless otherwise specified, the term “child” is used for individuals 0 to 18 years of age, and the term “adolescent” for those 13 to 18 years of age. •Anticipatory guidance regarding healthy eating and active lifestyle is recommended to prevent obesity.•Regular targeted screening for type 2 diabetes is recommended in children at risk.•Children with type 2 diabetes should receive care in consultation with an interdisciplinary pediatric diabetes healthcare team.•Early screening, intervention and optimization of glycemic control are essential, as the onset of type 2 diabetes during childhood is associated with severe and early onset of microvascular complications.Note: Unless otherwise specified, the term “child” is used for individuals 0 to 18 years of age, and the term “adolescent” for those 13 to 18 years of age. Type 2 diabetes in children has increased in frequency around the world over the past 2 decades (1Nadeau K. Dabelea D. Epidemiology of type 2 diabetes in children and adolescents.Endocr Res. 2008; 33: 35-58Crossref PubMed Scopus (40) Google Scholar). Children from ethnic groups at high risk for type 2 diabetes in their adult populations, namely, those of Aboriginal, African, Arabic, Hispanic or Asian descent, are disproportionally affected. A recent Canadian national surveillance study demonstrated a minimum incidence of type 2 diabetes in children and adolescents <18 years of age of 1.54 per 100 000 children per year (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). Significant regional variation was observed with the highest minimum incidence seen in Manitoba of 12.45 per 100 000 children per year. In this study, 44% of children with new onset type 2 diabetes were of Aboriginal heritage, 25% Caucasian, 10.1% Asian, 10.1% African/Caribbean and the remaining of other or mixed ethnic origin (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). Recent data from the United States (US) demonstrated an incidence of 8.1 per 100 000 person years in the 10- to 14-year age group and 11.8 per 100 000 person years in the 15- to 19-year group. In this study, the highest rates were found in American Indian, African American, Asian/Pacific Islander and Hispanic youth (in descending order), and the lowest incidence occurred in non-Hispanic white youth (3Dabelea D. Bell R.A. D'Agostino Jr., R.B. et al.Writing Group for the SEARCH for Diabetes in Youth Study GroupIncidence of diabetes in youth in the United States.JAMA. 2007; 297: 2716-2724Crossref PubMed Scopus (760) Google Scholar). Breastfeeding has been shown to reduce the risk of youth-onset type 2 diabetes in some populations (4Taylor J.S. Kacmar J.E. Nothnagle M. Lawrence R.A. A systematic review of the literature associating breastfeeding with type 2 diabetes and gestational diabetes.J Am Coll Nutr. 2005; 24: 320-326Crossref PubMed Scopus (93) Google Scholar). Obesity is a major modifiable risk factor for the development of type 2 diabetes (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). In 2004, 18% of Canadian children and adolescents were overweight and 8% were obese (5Shields M. Measured Obesity: Overweight Canadian children and adolescents. Nutrition: Findings from the Canadian Community Health Survey. Statistics Canada, Ottawa, ON2005Google Scholar). Studies on the prevention of obesity in children are limited and have generally not been demonstrated to be successful (6Oude Luttikhuis H. Baur L. Jansen H. et al.Interventions for treating obesity in children.Cochrane Database Syst Rev. 2009; : CD001872PubMed Google Scholar). In obese children, standard lifestyle interventions in the form of dietary recommendations and regular clinic visits have been shown to have little benefit for weight reduction (6Oude Luttikhuis H. Baur L. Jansen H. et al.Interventions for treating obesity in children.Cochrane Database Syst Rev. 2009; : CD001872PubMed Google Scholar). While data are limited, family-based lifestyle interventions with a behavioural component aimed at changes in diet and physical activity patterns have been shown to result in significant weight reduction in both children and adolescents (6Oude Luttikhuis H. Baur L. Jansen H. et al.Interventions for treating obesity in children.Cochrane Database Syst Rev. 2009; : CD001872PubMed Google Scholar). Health Canada–endorsed recommendations for physical activity and nutrition in children can be accessed on the Canadian Society for Exercise Physiology (http://www.csep.ca/english/view.asp?x=804) and Health Canada (http://www.hc-sc.gc.ca/fn-an/food-guide-aliment/choose-choix/advice-conseil/child-enfant-eng.php) websites (7Canadian Society for Exercise Physiology. Canadian Physical Activity Guidelines and Canadian Sedentary Behaviour Guidelines. Available at: http://www.csep.ca/english/view.asp?x=804. Accessed February 25, 2013.Google Scholar, 8Health Canada. Children—Canada's food guide. Available at: http://www.hc-sc.gc.ca/fn-an/food-guide-aliment/choose-choix/advice-conseil/child-enfant-eng.php. Accessed February 25, 2013.Google Scholar). The role of pharmacotherapy in the treatment of childhood obesity is controversial, as there are few controlled trials and no long-term safety or efficacy data (9Rogovik A.L. Chanoine J.P. Goldman R.D. Pharmacotherapy and weight-loss supplements for treatment of paediatric obesity.Drugs. 2010; 70: 335-346Crossref PubMed Scopus (28) Google Scholar). Several studies suggest that lifestyle changes plus pharmacotherapy may act synergistically when lifestyle intervention is aggressively pursued (10Freemark M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach.Diabetes Care. 2007; 30: 395-402Crossref PubMed Scopus (72) Google Scholar). Orlistat may be considered to aid in weight reduction and weight maintenance when added to a regimen of lifestyle intervention in adolescents (11McDuffie J.R. Calis K.A. Uwaifo G.I. et al.Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions.J Pediatr Endocrinol Metab. 2004; 17: 307-319Crossref PubMed Scopus (77) Google Scholar, 12Ozkan B. Bereket A. Turan S. Keskin S. Addition of orlistat to conventional treatment in adolescents with severe obesity.Eur J Pediatr. 2004; 163: 738-741Crossref PubMed Scopus (83) Google Scholar, 13Chanoine J.P. Hampl S. Jensen C. et al.Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial.JAMA. 2005; 293: 2873-2883Crossref PubMed Scopus (424) Google Scholar). Metformin has been observed to promote modest weight loss in small, short-term trials in children and adolescents (9Rogovik A.L. Chanoine J.P. Goldman R.D. Pharmacotherapy and weight-loss supplements for treatment of paediatric obesity.Drugs. 2010; 70: 335-346Crossref PubMed Scopus (28) Google Scholar). However, while both metformin and orlistat have potential for short-term positive effects on weight, glycemic control, insulin sensitivity and/or lipids, no pediatric studies have been performed to assess the prevention of diabetes or long-term complications. In obese adolescents with evidence of severe insulin resistance, pharmacological therapy with metformin or orlistat should only be considered after a comprehensive evaluation of the child's metabolic status, family history and review of lifestyle interventions. Due to a lack of data in prepubertal children, the use of antiobesity drugs should only be considered in this population within the context of a supervised clinical trial. Bariatric surgery in adolescents should be limited to exceptional cases and be performed only by experienced teams (14Sellers E.A. Pharmacotherapy and bariatric surgery for the treatment of obesity in children and adolescents, 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children.CMAJ. 2007; 176: S89-S91Google Scholar). The microvascular complications of type 2 diabetes have been identified at diagnosis, implying long-term, unrecognized hyperglycemia (15Pinhas-Hamiel O. Zeitler P. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents.Lancet. 2007; 369: 1823-1831Abstract Full Text Full Text PDF PubMed Scopus (313) Google Scholar). Children may also present with acute decompensation in diabetic ketoacidosis (DKA) and/or hyperosmolar coma. This argues for a systematic screening program aimed to identify children with type 2 diabetes in order to prevent acute, life-threatening presentation and to decrease the development of chronic complications. Although not proven in children, it is generally assumed that earlier diagnosis of diabetes will lead to interventions that will improve glycemic control and reduce the related short- and long-term complications (15Pinhas-Hamiel O. Zeitler P. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents.Lancet. 2007; 369: 1823-1831Abstract Full Text Full Text PDF PubMed Scopus (313) Google Scholar). Risk factors for the development of type 2 diabetes in children include a history of type 2 diabetes in a first- or second-degree relative (16Pinhas-Hamiel O. Dolan L.M. Daniels S.R. et al.Increased incidence of non-insulin-dependent diabetes mellitus among adolescents.J Pediatr. 1996; 128: 608-615Abstract Full Text PDF PubMed Scopus (944) Google Scholar), being a member of a high-risk population (e.g. people of Aboriginal, Hispanic, South Asian, Asian or African descent) (1Nadeau K. Dabelea D. Epidemiology of type 2 diabetes in children and adolescents.Endocr Res. 2008; 33: 35-58Crossref PubMed Scopus (40) Google Scholar), obesity (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar), impaired glucose tolerance (17Weiss R. Taksali S.E. Tamborlane W.V. et al.Predictors of changes in glucose tolerance status in obese youth.Diabetes Care. 2005; 28: 902-909Crossref PubMed Scopus (297) Google Scholar), polycystic ovary syndrome (PCOS) (18Palmert M.R. Gordon C.M. Kartashov A.I. et al.Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome.J Clin Endocrinol Metab. 2002; 87: 1017-1023Crossref PubMed Scopus (268) Google Scholar), exposure to diabetes in utero (19Dabelea D. Hanson R.L. Lindsay R.S. et al.Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.Diabetes. 2000; 49: 2208-2211Crossref PubMed Scopus (948) Google Scholar, 20Young T.K. Martens P.J. Taback S.P. et al.Type 2 diabetes mellitus in children: prenatal and early infancy risk factors among native Canadians.Arch Pediatr Adolesc Med. 2002; 156: 651-655Crossref PubMed Scopus (172) Google Scholar, 21Mendelson M. Cloutier J. Spence L. et al.Obesity and type 2 diabetes mellitus in a birth cohort of first nation children born to mothers with pediatric-onset type 2 diabetes.Pediatr Diabetes. 2011; 12: 219-228Crossref PubMed Scopus (33) Google Scholar), acanthosis nigricans (22Stoddart M.L. Blevins K.S. Lee E.T. et al.Cherokee Diabetes Study. Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in Cherokee Indians: the Cherokee Diabetes Study.Diabetes Care. 2002; 25: 1009-1014Crossref PubMed Scopus (86) Google Scholar), hypertension and dyslipidemia (23Weiss R. Dziura J. Burgert T.S. et al.Obesity and the metabolic syndrome in children and adolescents.N Engl J Med. 2004; 350: 2362-2374Crossref PubMed Scopus (2664) Google Scholar), and nonalcoholic fatty liver disease (NAFLD) (24Perseghin G. Bonfanti R. Magni S. et al.Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease.Am J Physiol Endocrinol Metab. 2006; 291: E697-E703Crossref PubMed Scopus (89) Google Scholar). Atypical antipsychotic medications are associated with significant weight gain, insulin resistance and impaired fasting glucose/type 2 diabetes in children (25Panagiotopoulos C. Ronsley R. Davidson J. Increased prevalence of obesity and glucose intolerance in youth treated with second-generation antipsychotic medications.Can J Psychiatry. 2009; 54: 743-749PubMed Google Scholar). Neuropsychiatric disorders and the use of neuropsychiatric medications are more common in obese children at diagnosis of type 2 diabetes compared to the general pediatric population (26Levitt Katz L.E. Swami S. Abraham M. et al.Neuropsychiatric disorders at the presentation of type 2 diabetes mellitus in children.Pediatr Diabetes. 2005; 6: 84-89Crossref PubMed Scopus (60) Google Scholar). In the recent national Canadian incidence study, the mean age of diagnosis of type 2 diabetes in youth was 13.7 years (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). However, 8% of all newly diagnosed children with type 2 diabetes were <10 years of age. In children of Aboriginal, Caucasian and Asian origin, 11%, 8.8% and 8.7%, respectively, presented at <10 years of age. Thus, consideration should be given for screening at a younger age in high-risk individuals (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). A fasting plasma glucose (FPG) is the recommended routine screening test for children, although ensuring a fasting state may be a challenge. The reproducibility of the FPG is high (27Libman I.M. Barinas-Mitchell E. Bartucci A. et al.Reproducibility of the oral glucose tolerance test in overweight children.J Clin Endocrinol Metab. 2008; 93: 4231-4237Crossref PubMed Scopus (130) Google Scholar). The oral glucose tolerance test may have a higher detection rate (28Sinha R. Fisch G. Teague B. et al.Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.N Engl J Med. 2002; 346: 802-810Crossref PubMed Scopus (1407) Google Scholar, 29Reinehr T. Andler W. Kapellen T. et al.Clinical characteristics of type 2 diabetes mellitus in overweight European Caucasian adolescents.Exp Clin Endocrinol Diabetes. 2005; 113: 167-170Crossref PubMed Scopus (28) Google Scholar) in children who are very obese (body mass index [BMI] ≥99th percentile for age and gender) and who have multiple risk factors for type 2 diabetes, but it has poor reproducibility (27Libman I.M. Barinas-Mitchell E. Bartucci A. et al.Reproducibility of the oral glucose tolerance test in overweight children.J Clin Endocrinol Metab. 2008; 93: 4231-4237Crossref PubMed Scopus (130) Google Scholar). Glycated hemoglobin (A1C) is not recommended as a method to diagnose type 2 diabetes in children. Otherwise, the diagnostic criteria for diabetes in children are the same as for adults. In most children, the presence of clinical risk factors, mode of presentation and early course of the disease indicate whether the child has type 1 or type 2 diabetes. However, differentiation may be difficult in some. Children with type 2 diabetes can present with DKA (30Pinhas-Hamiel O. Dolan L.M. Zeitler P.S. Diabetic ketoacidosis among obese African-American adolescents with NIDDM.Diabetes Care. 1997; 20: 484-486Crossref PubMed Scopus (136) Google Scholar, 31Sellers E.A. Dean H.J. Diabetic ketoacidosis: a complication of type 2 diabetes in Canadian aboriginal youth.Diabetes Care. 2000; 23: 1202-1204Crossref PubMed Scopus (38) Google Scholar). Testing for the absence of islet autoantibodies may be useful (32Dabelea D. Palmer J.P. Bennett P.H. et al.Absence of glutamic acid decarboxylase antibodies in Pima Indian children with diabetes mellitus.Diabetologia. 1999; 42: 1265-1266Crossref PubMed Scopus (33) Google Scholar, 33Sellers E. Eisenbarth G. Young T.K. Dean H.J. Diabetes-associated autoantibodies in aboriginal children.Lancet. 2000; 355: 1156Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 34Hathout E.H. Thomas W. El-Shahawy M. et al.Diabetic autoimmune markers in children and adolescents with type 2 diabetes.Pediatrics. 2001; 107: E102Crossref PubMed Scopus (134) Google Scholar). Fasting insulin levels are not helpful at diagnosis, as levels may be low due to glucose toxicity (35Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects.Endocr Rev. 1998; 19: 477-490Crossref PubMed Scopus (0) Google Scholar). DNA diagnostic testing for genetic defects in beta cell function should be considered in children who have a strong family history suggestive of autosomal dominant inheritance and who are lacking features of insulin resistance. This may be helpful when diabetes classification is unclear and may lead to more appropriate management (36Sellers E.A. Triggs-Raine B. Rockman-Greenberg C. Dean H.J. The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes.Diabetes Care. 2002; 25: 2202-2206Crossref PubMed Scopus (54) Google Scholar, 37Hattersley A.T. Molecular genetics goes to the diabetes clinic.Clin Med. 2005; 5: 476-481Crossref PubMed Scopus (45) Google Scholar). Children with type 2 diabetes should receive care in conjunction or consultation with an interdisciplinary pediatric diabetes healthcare team. The target glycated hemoglobin (A1C) for most children with type 2 diabetes should be ≤7.0%. To be effective, treatment programs for adolescents with type 2 diabetes need to address the lifestyle and health habits of the entire family, emphasizing healthy eating and physical activity (38Pinhas-Hamiel O. Standiford D. Hamiel D. et al.The type 2 family: a setting for development and treatment of adolescent type 2 diabetes mellitus.Arch Pediatr Adolesc Med. 1999; 153: 1063-1067Crossref PubMed Scopus (116) Google Scholar). While a recent systematic review found no good-quality studies directly assessing the effects of physical activity in youth with type 2 diabetes, it is reasonable to recommend (in the absence of direct evidence for this population) that children with type 2 diabetes strive to achieve the same activity level recommended for children in general: 60 minutes daily of moderate-to-vigorous physical activity and limiting sedentary screen time to no more than 2 hours per day (39Johnson S.T. Newton A.S. Chopra M. et al.In search of quality evidence for lifestyle management and glycemic control in children and adolescents with type 2 diabetes: a systematic review.BMC Pediatr. 2010; 10: 97Crossref PubMed Scopus (17) Google Scholar). Canadian physical activity guidelines for children and youth are available from the Canadian Society for Exercise Physiology (www.csep.ca). In a retrospective review of a predominantly First Nations population of youth with type 2 diabetes, target A1C (≤7%) was achieved and maintained on lifestyle monotherapy for 12 months after diagnosis in 54% of individuals who had presented with an A1C <9% at diagnosis (40Wittmeier K.D.M. Wicklow B.A. Sellers E.A.C. et al.Success with lifestyle monotherapy in youth with new-onset type 2 diabetes.Paediatr Child Health. 2012; 17: 129-132PubMed Google Scholar). In addition, psychological issues, such as depression, binge eating (41Wilfley D. Berkowitz R. Goebbel-Fabbri A. et al.TODAY Study GroupBinge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the TODAY study.Diabetes Care. 2011; 34: 858-860Crossref PubMed Scopus (84) Google Scholar) and smoking cessation, need to be addressed and interventions offered as required. In 1 retrospective cohort of pediatric patients, the prevalence of neuropsychiatric disorders at presentation of type 2 diabetes was 19.4% (26Levitt Katz L.E. Swami S. Abraham M. et al.Neuropsychiatric disorders at the presentation of type 2 diabetes mellitus in children.Pediatr Diabetes. 2005; 6: 84-89Crossref PubMed Scopus (60) Google Scholar). Insulin is required in those with severe metabolic decompensation at diagnosis (e.g. DKA, glycated hemoglobin [A1C] ≥9.0%, symptoms of severe hyperglycemia) but may be successfully weaned once glycemic targets are achieved, particularly if lifestyle changes are effectively adopted (42Sellers E.A. Dean H.J. Short-term insulin therapy in adolescents with type 2 diabetes mellitus.J Pediatr Endocrinol Metab. 2004; 17: 1561-1564Crossref PubMed Scopus (34) Google Scholar). There are limited data about the safety or efficacy of oral antihyperglycemic agents in the pediatric population, and none of the oral antidiabetic agents have been approved by Health Canada for use in children. Metformin has been shown to be safe in adolescents for up to 16 weeks, reducing A1C by 1.0% to 2.0% and lowering FPG with similar side effects as seen in adults (43Jones K.L. Arslanian S. Peterokova V.A. et al.Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.Diabetes Care. 2002; 25: 89-94Crossref PubMed Scopus (331) Google Scholar). Glimepiride has also been shown to be safe and effective in adolescents for up to 24 weeks, reducing A1C (−0.54%) to a similar extent as metformin (−0.71%) but resulting in a significant weight increase of 1.3 kg (44Gottschalk M. Danne T. Vlajnic A. Cara J.F. Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study.Diabetes Care. 2007; 30: 790-794Crossref PubMed Scopus (116) Google Scholar). The Treatment Options for Type 2 Diabetes in Youth (TODAY) study was a multicentre trial that randomized youth with type 2 diabetes to metformin alone, metformin plus a lifestyle intervention, or metformin plus rosiglitazone (45Zeitler P. Hirst K. et al.TODAY Study GroupA clinical trial to maintain glycemic control in youth with type 2 diabetes.N Engl J Med. 2012; 366: 2247-2256Crossref PubMed Scopus (627) Google Scholar). The study population included youth 10 to 17 years of age with a mean diabetes duration of 7.8 months and A1C <8%. In the entire study population, treatment failure (defined as A1C ≥8% over 6 months or sustained metabolic decompensation requiring insulin therapy) occurred in 51.7% of the metformin group, 46.6% of the metformin plus lifestyle group, and 38.6% of the metformin plus rosiglitazone group (metformin-rosiglitazone vs. metformin alone; p=0.006). However, there were important differences in response between genders and ethnic groups. This study demonstrated that a significant proportion of youth with type 2 diabetes requires aggressive intervention early in the course of the disease, and treatment failure is common. Serious adverse events thought to be related to study medication were uncommon over mean follow-up of 3.9 years. Given the concerns raised around the long-term safety of rosiglitazone since the start of this trial, it is premature to recommend its routine use in children on the basis of this study. A pharmacokinetic and safety study of a single injection of exenatide in 13 adolescents being treated with metformin demonstrated good tolerability and improved postprandial glucose levels (46Malloy J. Capparelli E. Gottschalk M. et al.Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study.Clin Ther. 2009; 31: 806-815Abstract Full Text PDF PubMed Scopus (30) Google Scholar). The experience of bariatric surgery in adolescents with type 2 diabetes is very limited with specific eligibility criteria (BMI >35 kg/m2, Tanner stage IV or V, and skeletal maturity). A single retrospective case series of 11 postpubertal adolescents with type 2 diabetes who underwent roux-en-Y gastric bypass demonstrated significant improvements in BMI, glycemic control, serum lipid levels and blood pressure (BP) compared to 67 adolescents who were medically managed over 1 year (47Inge T.H. Miyano G. Bean J. et al.Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk factors after surgical weight loss in adolescents.Pediatrics. 2009; 123: 214-222Crossref PubMed Scopus (146) Google Scholar). Notably, 10 of the 11 surgically treated youth experienced remission of their diabetes without the need for medication. The recommendations for influenza and pneumococcal immunization in Canada do not address the issue of type 2 diabetes in children, and there are no studies evaluating the usefulness of the influenza or pneumococcal vaccine in this population. There is no reason not to manage these children in a similar fashion to those with type 1 diabetes in whom influenza immunization is recommended to be offered as a way to avoid an intercurrent illness that could complicate diabetes management. Some children with type 2 diabetes may also have other factors (e.g. Aboriginal heritage) that may place them at higher risk of increased influenza- and pneumococcal-related morbidity (48Advisory Committee on Immunization Practices Preventing pneumococcal disease among infants and young children. Recommendations of the advisory committee on immunization practices (ACIP).MMWR Recomm Rep. 2000; 49: 1-35Google Scholar, 49Crighton E.J. Elliott S.J. Moineddin R. Kanaroglou P. Upshur R. A spatial analysis of the determinants of pneumonia and influenza hospitalizations in Ontario (1992-2001).Soc Sci Med. 2007; 64: 1636-1650Crossref PubMed Scopus (48) Google Scholar, 50Fanella S.T. Pinto M.A. Bridger N.A. et al.Pandemic (H1N1) 2009 influenza in hospitalized children in Manitoba: nosocomial transmission and lessons learned from the first wave.Infect Control Hosp Epidemiol. 2011; 32: 435-443Crossref PubMed Scopus (19) Google Scholar). Short-term complications of type 2 diabetes in children include DKA and hyperglycemic hyperosmolar state (HHS); 10% of Canadian youth present with DKA at the time of diagnosis (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study.Diabetes Care. 2010; 33: 786-791Crossref PubMed Scopus (156) Google Scholar). High mortality rates (up to 37% in 1 series) have been reported in youth presenting with combined DKA and HHS at onset of type 2 diabetes (51Rosenbloom A.L. Hyperglycemic hyperosmolar state: an emerging pediatric problem.J Pediatr. 2010; 156: 180-184Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar, 52Fourtner S.H. Weinzimer S.A. Levitt Katz L.E. Hyperglycemic hyperosmolar non-ketotic syndrome in children with type 2 diabetes.Pediatr Diabetes. 2005; 6: 129-135Crossref PubMed Scopus (71) Google Scholar, 53Carchman R.M. Dechert-Zeger M. Calikoglu A.S. Harris B.D. A new challenge in pediatric obesity: pediatric hyperglycemic hyperosmolar syndrome.Pediatr Crit Care Med. 2005; 6: 20-24Crossref PubMed Scopus (45) Google Scholar). Evidence suggests that early-onset type 2 diabetes in adolescence is associated with severe and early-onset microvascular complications, including retinopathy, neuropathy and nephropathy (54Krakoff J. Lindsay R.S. Looker H.C. et al.Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset type 2 diabetes.Diabetes Care. 2003; 26: 76-81Crossref PubMed Scopus (114) Google Scholar, 55Yokoyama H. Okudaira M. Otani T. et al.Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications.Diabetes Care. 1997; 20: 844-847Crossref PubMed Scopus (92) Google Scholar, 56Eppens M.C. Craig M.E. Cusumano J. et al.Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes.Diabetes Care. 2006; 29: 1300-1306Crossref PubMed Scopus (345) Google Scholar). Although neither retinopathy nor neuropathy has been described in adolescents with type 2 diabetes at diagnosis, 1 study found that 1 in 5 youth with type 2 diabetes had peripheral nerve abnormalities, and more than half had autonomic neuropathy after a median duration of diabetes of 1.3 years (56Eppens M.C. Craig M.E. Cusumano J. et al.Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes.Diabetes Care. 2006; 29: 1300-1306Crossref PubMed Scopus (345) Google Scholar). Micro- or macroalbuminuria has been noted in 14.2% of Canadian youth at diagnosis (2Amed S. Dean H.J. Panagiotopoulos C. et al.Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance st