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Screening and Diagnosis of Type 1 Diabetes
According to 2002 US prevalence data, approximately 210,000 people under the age of 20 years have diabetes (0.2 6% of the aged-based population). It is estimated that type 1 diabetes affects approximately 1 out of every 400 to 500 children and adolescents and accounts for 5% to 10% of all diagnosed cases of diabetes.[1] Type 1 diabetes arises in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin-secreting beta cells.[2] Generally, people with type 1 diabetes present with acute symptoms of diabetes and markedly elevated blood glucose levels.[3,4] Common symptoms of hyperglycemia include polyuria, polydipsia, weight loss, sometimes polyphagia, and blurred vision.[5] Screening for type 1 diabetes involves a more complex approach compared with type 2 diabetes. However, several theories suggest that early recognition and treatment intervention of high-risk individuals could possibly delay or halt the progression of beta-cell destruction.[2,6] Currently accepted guidelines for screening and diagnosis of type 1 diabetes are presented here.
Screening for type 1 diabetes
The purpose of screening for type 1 diabetes is to identify individuals at high risk for developing the disease and to provide appropriate referrals for individuals who screen positive.[6] Individuals at high risk for developing type 1 diabetes are identified in Table 1. The American Diabetes Association (ADA) recommends screening only for high-risk individuals provided that individuals that screen positive are referred to centers participating in cooperative intervention studies or other scientific investigations.[6] Individuals at increased risk of developing type 1 diabetes can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islets and by genetic markers.[5] Markers of cellular-mediated autoimmune destruction of the pancreatic beta cells can be analyzed through laboratory testing. Table 2 lists these common markers of autoimmune destruction. The presence of such markers before the development of overt disease can identify individuals at risk.[7] One and usually more of these autoantibodies are present in 85% to 90% of individuals when fasting hyperglycemia is initially detected.[5] Routine immune marker screening is currently not recommended outside of a clinical trial setting based on the reasons provided in Table 3.
Table 1. Factors associated with a high risk of type 1 diabetes[8,9]
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Family member(s) with type 1 diabetes:
Mother diabetic, child has 2% risk
Father diabetic, child has 6% risk
Sibling diabetic, child has 6% risk
Fraternal twin diabetic, other twin has 11% risk
Identical twin diabetic, other twin has 50% risk
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Concomitant autoimmune conditions:
Hashimoto's disease
Graves' disease
Addison's disease
Pernicious anemia
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Born to:
Older mother
Mother with preeclampsia during pregnancy
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Ethnicity:
Northern European
Mediterranean
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Individuals expressing more than 1 autoantibody (ICA, IAA, GAD, IA-2) |
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Viral infections during childhood:
Coxsackie B infections
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Children who stop breast-feeding before 3 months of age (given cow's milk instead)* |
*Only hypothesized; doctors uncertain whether cow's milk actually plays a role in the development of type 1 diabetes
Table 2. Markers of autoimmune beta-cell destruction[5]
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Islet cell autoantibiodies
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Antibodies to insulin |
Autoantibodies to glutamic acid decarboxylase (GAD65) |
Autoantibodies to tyrosine phosphatase IA-2 and IA-2 beta |
Diagnosis of type 1 diabetes
There are 3 blood glucose assays used to diagnose diabetes: random, fasting (fasting plasma glucose or FPG), or 2 hours after 75 g oral glucose load (oral glucose tolerance or OGTT).[10] Diagnosis should be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present. Although the OGTT is more sensitive and modestly more specific than FPG at diagnosing diabetes, OGTT is poorly reproducible and rarely performed in practice. Since FPG is easy to use, is accepted by patients, and has a lower cost, FPG is considered the preferred screening and diagnostic test by the ADA. Current criteria for the diagnosis of diabetes are shown in Table 3.
Table 3. ADA criteria for the diagnosis of diabetes[3,4]
- Symptoms of diabetes and a casual plasma glucose ≤200 mg/dL (11.1 mmol/L)
o Symptoms = polyuria, polydipsia, and unexplained weight loss
o Casual = any time of day without regard to time since last meal
OR
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- FPG ≤126 mg/dL (7.0 mmol/L)
o Fasting = no caloric intake for at least 8 hours
OR
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- 2-h PG ≤200 mg/dL (11.1 mmol/L) during an OGTT. Test should be performed as described by WHO using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water
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Typically, children with type 1 diabetes present with severe symptoms, very high blood glucose levels, marked glycosuria, and ketonuria. Children are generally diagnosed with diabetes using blood glucose measurements, and treatment is initiated immediately if marked hyperglycemia is present. An OGTT is neither necessary nor appropriate for diagnosis in such circumstances. A smaller portion of children and adolescents present with less severe symptoms and may require fasting blood glucose measurement and/or OGTT for diagnosis.[11]
Diagnosis of type 1 diabetes in asymptomatic individuals should never be made on the basis of a single abnormal blood glucose value. For asymptomatic individuals, at least one additional plasma/blood glucose test result with a value in the diabetic range is essential, either fasting, from a random (casual) sample, or from an OGTT. If such samples fail to confirm diagnosis, it is usually advisable to maintain surveillance with periodic re-evaluation until the diagnostic situation becomes evident. In these situations, the clinician should consider such factors as ethnicity, family history, age, adiposity, and concomitant disorders, before deciding on a diagnostic or therapeutic course of action.[11]
References
- American Diabetes Association. National diabetes fact sheet. Available at: http:www.diabetes.org/diabetes-statistics/national-diabetes-fact-sheet.jsp. Accessed January 24, 2006.
- Skyler JS. The importance of the Diabetes Prevention Trial-Type 1. Medscape Diab Endocr. 2000;2. Available at: http://www.medscape.com/viewarticle/407923. Accessed November 22, 2004.
- American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2004;27(suppl 1):S15-S35.
- American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27(suppl 1):S5-S10.
- American Diabetes Association. Prevention of type 1 diabetes. Diabetes Care. 2004;27(suppl 1):S133.
- American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26(suppl 1):S5-S20.
- Leslie RD, Castelli MD. Age-Dependent Influences on the Origins of Autoimmune Diabetes. Evidence and Implications. Diabetes. 2004;53:3033-3040.
- Adams A. What is type 1 diabetes? Available at: http://www.genetichealth.com/DBTS_What_Is_Type_1_Diabetes.shtml. Accessed November 23, 2004.
- Balkau B, Eschwege E. The diagnosis and classification of diabetes and impaired glucose regulation. In: Pickup JC, Williams G, eds. Textbook of Diabetes. Vol 1. 3rd ed. Malden, Ma.: Blackwell Science; 2003:2.6.
- World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabet Med. 1998;15:539-553.
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