Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents
Historically, type 2 diabetes is well known as an adult-onset disease; however, lately, the incidence of the disease is reported to be increasing in children and adolescents dramatically worldwide with the highest prevalence in those of American-Indian, Hispanic, African-American and Asian descent.(1) An increased prevalence of T2DM has also been reported in Japanese, Canadian, Australian and Libyan children.(2) The SEARCH study currently provides the best prevalence data of paediatric T2DM in the US. According to these data the prevalence amongst children and young adults below 20 years of age in 2001 was about 20.000 or cases per 10,000 US youth. (3)
Despite the increased prevalence of T2DM in the paediatric population, there is limited information about the relative effectiveness of treatment approaches. Furthermore, the treatment options are much more limited in adolescents than adults with T2DM.(4)
The ideal goal of treatment is normalization of blood glucose values and HbA1c. The ultimate goal of treatment is to decrease the risk of the acute and chronic complications associated with diabetes. Pharmacological therapy is recommended for children who are unable to achieve satisfactory glycaemic control through physical activity and diet.(5)
Metformin is the initial pharmacological treatment of choice if metabolically stable. The Global IDF/ISPAD Guideline for Diabetes in Childhood and Adolescence, published in 2011 and the recent Clinical Practice Guideline from the American Academy of Paediatrics, published in 2013 stated that initial care of T2DM will depend on the severity of symptoms at presentation.
Insulin may be required for initial metabolic stabilisation if significant hyperglycaemia (HbA1c > 9 % or plasma BG concentrations > 250mg/dl and ketosis is present, even in the absence of ketoacidosis.(6) Otherwise, there is little evidence that insulin is superior to oral agents for initial treatment of T2D in children.
Currently, there are six types of glucose lowering oral agents for the treatment of T2DM: biguanides; sulfonylureas; meglitinides; alpha glucosidase inhibitors; thiazolidinediones; DPP-4inhibitors. Because the pathophysiology of T2DM in children and adolescents appears to be similar to that of T2DM in adults with only few differences (faster decline in beta cell function, different response to treatment in terms of durability of the efficacy and potential differences in the safety profile related to developmental aspects – pubertal, bone and neurocognitive development, faster progression from Impaired Glucose Tolerance to T2DM) it is reasonable to assume that oral agents will be effective in children. (7) Yet, the efficacy and safety data are not available for children nor are any of the oral drugs FDA approved for use in children. In European Union, the only approved drugs in paediatrics T2DM are metformin and insulin.
Most medications used for T2DM have been tested for safety and efficacy only in people older than 18 years, and there is scant scientific evidence for optimal management of children with T2DM. Similarly, the diabetes education materials designed for paediatric patients are directed primarily to families of children with type 1 diabetes mellitus and emphasize insulin treatment and glucose monitoring, which may or may not be appropriate for children with T2DM.
Once again, paediatric diabetes practitioners are left with just metformin and insulin for adolescents with T2DM. Early treatment is essential for paediatric patients in order to slow or delay progression of the disease and its complications. Further research is needed to determine the natural progression of T2DM and treatment approaches in paediatric patients. (8)
Clinicians should remain alert to new developments with regard to treatment of T2DM.
- Dabelea D, Hanson RL, Bennett PH, et al. Increasing prevalence of type II diabetes in American Indian children. West J Med 1998; 168: 11-16
- Kitagawa T, Owada M, Urakami T, et al. Increased incidence of non-insulin dependent diabetes mellitus among Japanese school children correlates with an increased intake of animal protein and fat. Clinical Pediatrics 1998; 37: 111-16
- SEARCH for Diabetes in Youth Study Group, Liese AD, D’Agostino RB, Hamman RF, Kilgo PD, Lawrence JM, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006 Oct; 118(4):1510-8.
- TODAY Study Group, Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatric Diabetes. 2007 Apr; 8 (2): 74-87
- Eva M. Vivian. Type 2 Diabetes in Children and Adolescents- The Next Epidemic? Current Medical Research and Opinion. 2006; 22(2):297-306
- Global IDF/ISPAD Guideline for Diabetes in childhood and adolescence, 2011, p 22
- DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 131:281-303, 1999
- Kenneth C. Copeland, Janet Silverstein, Kelly R. Moore, Greg E. Prazar, Terry Raymer, Richard N. Shiffman, Shelley C. Springer, Vidhu V. Thaker, Meaghan Anderson, Stephen J. Spann and Susan K. Flinn. Management of Newly Diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescents. Pediatrics 2013;131;364; originally published online January 28, 2013; DOI: 10.1542/peds.2012-3494