Type 1 diabetes mellitus
Accounting for only 5%-10% of all diabetes cases,1 T1DM is caused by the immune-mediated destruction of the pancreatic beta-cells, resulting in an absolute deficiency of insulin secretion. Such environmental triggers as particular viruses can instigate the immune-mediated response, which leads to T1DM in genetically predisposed individuals.6 Treatment includes insulin administration to replace/supplement the insufficiency of secreted insulin.
Type 2 diabetes mellitus
Accounting for 90%-95% of all diabetes cases,1 T2DM is caused by a complex combination of metabolic disorders arising from such defects as cellular insulin resistance, increased hepatic glucose production and relative decreased pancreatic insulin secretion. There is a known strong genetic predisposition for T2DM among family members.6 Treatment strategies for T2DM are based on the individual’s ability to achieve glycemic goals.
The American Academy of Clinical Endocrinologists’ (AACE) diabetes-management guidelines are based on HbA1c levels and clinical symptoms (Table 3).7 Typically, an insulin sensitizer (e.g., metformin) coupled with lifestyle changes is the first line of treatment for T2DM. However, the use of metformin has only been able to lead to a 1%-2% reduction in HbA1c levels.7
According to the AACE guidelines, insulin should be initiated for HbA1c levels >10% to control hyperglycemia and reverse glucose toxicity.7 Insulin treatment may be modified as glucose toxicity resolves and clinical condition improves. In light of Adam’s extremely elevated HbA1c level, insulin should have been considered.
When considering initiating pharmacologic therapy for the management of T2DM, keep in mind that most oral agents used in adults are not approved for use in children. All pharmacologic interventions should be monitored closely and adjusted as necessary to ensure adequate effect of treatment.
In cases of T1DM, one or more of the diabetes autoantibodies will be present in 95% of those affected at the time of initial diagnosis.5 With T2DM, the autoantibodies are typically absent.
Four autoantibodies demonstrate the beta-cell autoimmunity of T1DM: While the islet cell autoantibody is positive in 70% to 80% new-onset cases of T1DM,8 it is not specific to the beta-cell. The GAD autoantibody, detected in 80% of new-onset T1DM cases, is specific to the beta-cell protein5 and is the most commonly detected autoantibody. Protein tyrosine phosphatase-like protein (IA-2) autoantibodies are antigen-specific islet autoantibodies and are frequently detected in children with T1DM (about 60% at diagnosis).5,8
Insulin autoantibodies are present in 50% of children with T1DM at the time of diagnosis. Insulin autoantibodies cannot distinguish between endogenous and exogenous insulin and are a poor test for those on insulin therapy. In fact, individuals who have received exogenous insulin therapy for more than two to three weeks may have positive insulin autoantibodies on analysis.6
Autoantibodies may even be present in individuals without diabetes. Presence of autoantibodies in the absence of diabetes does not guarantee the development of T1DM. The risk of T1DM is directly proportional to the number and titer of autoantibodies present.9 The presence of GAD autoantibody and IA-2 autoantibody predicts beta-cell failure, thus demonstrating T1DM.8 The positivity of autoantibodies decreases over time in T1DM, so there is no need to measure autoantibodies years after onset.
Putting it all together
In the clinical setting, how can one differentiate between the onset of T1DM and T2DM in children? Laboratory studies can be helpful (Table 4). Keep in mind that autoantibody results can take up to two weeks. Clinical presentation, current glucose level, presence of ketones, and HbA1c level can help the clinician determine how best to proceed with the initial stabilization and medical management of a child with diabetes.
In Adam’s case, clinical presentation warranted the initiation of insulin based on the AACE management guidelines.7 His extremely elevated HbA1c level demonstrated a degree of glucose toxicity. Two to three months of insulin was recommended to combat glucose toxicity and to allow time for laboratory evaluation to determine proper diagnosis (T1DM vs. T2DM). Of course, pharmacologic intervention should be considered in addition to glucose/ketone monitoring strategies, dietary intervention/instruction, and management of daily activities in individuals with either T1DM or T2DM.
Children with suspected T2DM and HbA1c <10% can be managed less aggressively according to their clinical presentation and initial laboratory analyses. However, if laboratory analyses demonstrate the presence of diabetes autoantibodies, insulin should be initiated to prevent DKA, which can result from a delay in treatment.
Dr. Scott is an assistant professor and pediatric BSN-DNP coordinator at the University of Kentucky College of Nursing in Lexington.
- National Diabetes Education Program. Overview of diabetes in children and adolescents.
- National Institute of Diabetes and Digestive and Kidney Diseases. National diabetes statistics, 2011.
- Bell RA, Mayer-Davis EJ, Beyer JW, et al. Diabetes in non-Hispanic white youth: prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2009;32:S102-S111.
- Rai VM, Balachandran C. Generalized acanthosis nigricans in childhood. Dermatol Online J. 2006;12:14.
- Taplin CE, Barker JM. Autoantibodies in type 1 diabetes. Autoimmunity. 2008 Feb;41:11-8.
- Centre for Genetics Education. Diabetes types 1 and 2 and inherited predisposition.
- Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13 Suppl 1:1-68.
- American Association of Clinical Chemistry. Diabetes-related autoantibodies.
- Borg H, Gottsäter A, Fernlund P, Sundkvist G. A 12-year prospective study of the relationship between islet antibodies and beta-cell function at and after the diagnosis in patients with adult-onset diabetes. Diabetes. 2002;51:1754-1762.
All electronic documents accessed October 3, 2011.