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Test ID: DME    
Diabetes Mellitus Type 1 Evaluation

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Useful For Suggests clinical disorders or settings where the test may be helpful

Distinguishing type 1 from type 2 diabetes mellitus

 

Identifying individuals at risk of type 1 diabetes (including high-risk relatives of patients with diabetes)

 

Predicting future insulin requirement treatment in patients with adult-onset diabetes

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Islet cell autoantibodies were first recognized to be associated with type 1 diabetes mellitus in 1974. Several islet cell-specific autoantigens have been identified in recent years.(1) These include glutamic acid decarboxylase 65 (GAD65), the tyrosine phosphatase-related islet antigen 2 (IA-2), and insulin. The sensitivities of these autoantibodies for type 1 diabetes in an international collaborative study were 91% (GAD65 antibody), 74% (IA-2 antibody), and 49% (insulin antibody) when tested in isolation.(2) When tested in combination, the combined sensitivity for type 1 diabetes was up to 98%, with a specificity of 98% to 100%.(2) These autoantibodies also are detectable before the clinical onset of diabetes. Prospective studies in relatives of patients with type 1 diabetes have shown that the detection of 1 or more islet autoantibodies is an early marker of progression to type 1 diabetes. Among first-degree relatives of those with type 1 diabetes, the cumulative risk of developing diabetes at 5 years after testing was 17% if seropositive for 1 antibody, 39% if seropositive for 2 antibodies, and 70% if seropositive for 3 antibodies.(3) Autoantibody profiles identifying patients destined to develop type 1 diabetes are usually detectable in serum before age 3. Some patients with type 1 diabetes are initially misdiagnosed as having type 2 diabetes because of symptom onset in adulthood, societal obesity, and initial insulin-independence. Detection of 1 or more islet autoantibodies allows identification of patients with "latent autoimmune diabetes in adulthood" amongst those with presumed type 2 diabetes.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

GLUTAMIC ACID DECARBOXYLASE (GAD65) ANTIBODY

< or =0.02 nmol/L

Reference values apply to all ages.

 

INSULIN ANTIBODIES

< or =0.02 nmol/L

Reference values apply to all ages.

 

ISLET ANTIGEN 2 (IA-2) ANTIBODY

< or =0.02 nmol/L

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

Seropositivity for 1 or more islet cell autoantibodies is supportive of:

-A diagnosis of type 1 diabetes. Only 2% to 4% of patients with type 1 diabetes are antibody negative; 90% have more than 1 antibody marker, and 70% have 3 markers.(1) Patients with gestational diabetes who are antibody seropositive are at high risk for diabetes postpartum. Rarely, diabetic children test seronegative, which may indicate a diagnosis of maturity-onset diabetes of the young in clinically suspicious cases.

-A high risk for future development of diabetes. Among 44 first degree relatives of patients with type 1 diabetes, those with 3 antibodies had a 70% risk of developing type 1 diabetes within 5 years.(3)

-A current or future need for insulin therapy in patients with diabetes. In the UK Prospective Diabetes Study, 84% of those classified clinically as having type 2 diabetes and seropositive for glutamic acid decarboxylase 65 required insulin within 6 years, compared to 14% that were antibody negative.(4)

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Negative results do not exclude the diagnosis of or future risk for type 1 diabetes mellitus. The risk of developing type 1 diabetes may be stratified further by testing for antibody targeting zinc transporter 8 (ZnT8) and HLA genetic markers. Careful monitoring of hyperglycemia is the mainstay for determining the requirement for insulin therapy.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Bingley PJ: Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab 2010;95:25-33

2. Verge CF, Stenger D, Bonifacio E, et al: Combined use of autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell antibodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes 1998;47:1857-1866

3. Bingley PJ, Gale EA: Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk. Diabetologia 2006;49:881-890

4. Turner R, Stratton I, Horton V, et al: UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997;350:1288-1293