Islet cell autoantibody testing is not always reliable, and the results are not immediately available. Thus, the physician must depend on clinical judgment in classifying new-onset diabetes patients. The pathways in bold in the decision trees provided in Figure 1 indicate the most likely outcomes. Classification may only be possible after months or longer of follow-up.
In African American children with new, acute-onset diabetes, islet autoantibody testing can identify many of the children who have type 1 diabetes. If islet autoantibody studies are negative, a family history of early-onset diabetes in 3 or more generations suggests ADM. In the absence of such a family history, the absence of obesity suggests type 1 diabetes. Some children with new-onset type 1 diabetes, however, are overweight, because of the increasing prevalence of obesity in the society as a whole. Ketoacidosis or ketosis is not useful for distinguishing between type 1 diabetes, ADM, and type 2 diabetes, because as many as 25% of children with type 2 diabetes are initially seen with DKA and 40% with ketonuria (29,30). Obese children with insidious onset diabetes, commonly detected incidentally, most likely have type 2 diabetes. A family history of diabetes affecting at least one parent is found in 50% to 80%, and 75% to 100% have a first or second degree relative with type 2 diabetes (30).
The presence of islet cell autoantibodies strongly argues in favor of type 1 diabetes. Specific autoantibodies to insulin, to glutamic acid dehydrogenase (GAD), or to the tyrosine phosphatase insulinoma antibody (IA)-2 and IA-2P, are seen at the time of diagnosis in 85% to 98% of patients with immune-mediated type 1 diabetes (31). Because MODY is rare, there is no routine value in testing for HNF-4 alpha, glucokinase, HNF-1 alpha, 1PF-1, or HNF-1 beta mutations (26). Mitochondrial mutations account for < 2% of clinical type 2 diabetes in adults; therefore, studies of the mitochondrial genome and identification of genetic defects responsible for MODY remain primarily research tools (6,25).
The Florida experience noted earlier provides a perspective on the difficulty of initial classification in a relatively small subset of patients and the importance of follow-up observation with reconsideration of classification. Of the 723 patients newly diagnosed during the five-year study period, 605 were classified as type 1 and 77 as type 2; 41 were considered either atypical or remained of uncertain classification. Of those initially diagnosed as type 1 diabetes, 17 (2.8%) were subsequently reclassified as type 2 diabetes, and 6 (8%) of those initially diagnosed as type 2 diabetes were reclassified as type 1 diabetes. Most of the 17 reclassified as type 2 had been diagnosed in DKA or with ketosis (9).
TABLE 2 Criteria for the Diagnosis of Diabetes Mellitusa
Symptoms of diabetes plus random plasma glucose concentration > 200 mg/dL (ll.l mmol/L). Casual is defined as anytime of day without regard to time since last meal. Typical symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.
FPG > 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h. or
2-h PG >200 mg/dL (ll.l mmol/L) during an OGTT. The test should be performed using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water for those weighing > 43 kg and 1.75 g/kg for those weighing <43 kg.
aIn the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day. The third measure (OGTT) is not recommended for routine clinical use. Abbreviations: FPG, fasting plasma glucose; OGTT, oral glucose tolerance test. Source: From Ref. 1.
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