INTRODUCTION
Incidence of diabetes is on steep rise throughout the world and so as diabetes in children. Approximately, 90% of the children with diabetes have type 1 diabetes. Early diagnosis and differentiating the type of diabetes can have therapeutic implications. In this chapter, we will see the etiological and clinical classification of diabetes in children.
DEFINITION
The term diabetes mellitus describes a complex metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Inadequate insulin secretion and/or diminished tissue responses to insulin in the complex pathways of hormone action result in deficient insulin action on target tissues, which leads to abnormalities of carbohydrate, fat, and protein metabolism. Impaired insulin secretion and/or action may coexist in the same patient.1,2
CLASSIFICATION
The type of diabetes assigned to a young person at diagnosis is typically based on their characteristics at presentation, however, increasingly the ability to make a clinical diagnosis has been hampered by factors including the increasing prevalence of overweight in young people with type 1 diabetes,3,4 and the presence of diabetic ketoacidosis in some young people at diagnosis of type 2 diabetes.5,6
In addition, the presentation of a familial form of mild diabetes during adolescence should raise the suspicion of monogenic diabetes, which accounts for 1–4% of pediatric diabetes cases.7–104
The etiological classification of diabetes is shown in box 1, which is based on the American Diabetes Association classification.2
The differentiation between type 1, type 2, monogenic, and other forms of diabetes has important implications for both therapeutic decisions and educational approaches. Differentiating the type of diabetes is very important as it has therapeutic implications. There are specific tests that can help in confirming the type of diabetes:
- Detection of autoantibodies: The presence of glutamic acid decarboxylase, IA2, IAA, and/or ZnT8 for type 1 diabetes. These autoantibodies are present in 85–90% cases with fasting hyperglycemia
- Elevated fasting C-peptide: To distinguish young people with non-autoimmune, insulin resistant type 2 diabetes from type 1 diabetes.
Measuring C-peptide levels is not recommended in early stage or acute phase as there can be an overlap in insulin or C-peptide between type 1 and type 2 in first year after diagnosis. In insulin treated patients measuring C-peptide when the glucose is sufficiently high (>8 mmol/L) to stimulate C peptide will detect if endogenous insulin secretion is still present. This is not common beyond the remission phase (2–3 years) in children with T1D.6
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In cases where autoantibodies are not detected, one should look for the following:
- Family history of diabetes if anybody in the family has autosomal dominant diabetes
- Diagnosis of diabetes in first 6 months of life
- Nonprogressing mild fasting plasma glucose (100–150 mg/dL), in young, non-obese, and asymptomatic
- Associated conditions such as deafness, optic atrophy, or syndromic features
- A history of exposure to drugs, toxic to β-cells.
Immediate molecular genetic testing should be done in all patients diagnosed with diabetes in the first 6 months of life to define if it is neonatal diabetes mellitus, as type 1 diabetes is extremely rare in this subgroup. Beyond the age of 6 months, genetic testing should be limited to those patients who are negative for autoantibodies.
Characteristic features of youth onset type 1 diabetes in comparison with type 2 diabetes and monogenic diabetes are shown in table 1.
CONCLUSION
Genetic testing plays an important role in defining the type of childhood diabetes. Even in resource limited settings, full efforts should be made for performing all necessary tests in order to reach at correct diagnosis.7
REFERENCES
- World Health Organization. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia: Report of a WHO/IDF Consultation. Geneva, Switzerland: World Health Organization; 2006.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37:S81–90.
- Islam ST, Abraham A, Donaghue KC, Chan AK, Lloyd M, Srinivasan S, et al. Plateau of adiposity in Australian children diagnosed with type 1 diabetes: a 20-year study. Diabet Med. 2014;31:686–90.
- Kapellen TM, Gausche R, Dost A, Wiegand S, Flechtner-Mors M, Keller E, et al. Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database. J Pediatr Endocrinol Metab. 2014;27:209–14.
- Rewers A, Klingensmith G, Davis C, Petitti DB, Pihoker C, Rodriguez B, et al. Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study. Pediatrics. 2008;121:e1258–66.
- Dabelea D, Rewers A, Stafford JM, Standiford DA, Lawrence JM, Saydah S, et al. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014;133:e938–45.
- Fendler W, Borowiec M, Baranowska-Jazwiecka A, Szadkowska A, Skala-Zamorowska E, Deja G, et al. Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia. 2012;55:2631–5.
- Irgens HU, Molnes J, Johansson BB, Ringdal M, Skrivarhaug T, Undlien DE, et al. Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia. 2013;56:1512–9.
- Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, Dolan LM, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab. 2013;98:4055–62.
- Galler A, Stange T, Muller G, Näke A, Vogel C, Kapellen T, et al. Incidence of childhood diabetes in children aged less than 15 years and its clinical and metabolic characteristics at the time of diagnosis: data from the Childhood Diabetes Registry of Saxony, Germany. Horm Res Paediatr. 2010;74:285–91.
- Zeitler P, Fu J, Tandon N, Nadeau K, Urakami T, Barrett T, et al. Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2014;15(Suppl 20):26–46.
- Rubio-Cabezas O, Hattersley AT, Njølstad PR, Mlynarski W, Ellard S, White N, et al. ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2014;15(Suppl 20):47–64.
- Craig ME, Jefferies C, Dabelea D, Balde N, Seth A, Donaghue KC, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2014;15(Suppl 20):4–17.