Semi-quantitative Enzyme-Linked Immunosorbent Assay
Quantitative Enzyme-Linked Immunosorbent Assay
Useful to establish autoimmune etiology in previously diagnosed T1DM.
Semi-Quantitative Radioimmunoassay
- Determine presence of antibodies to endogenous or exogenous insulin analogues
- Testing not recommended for patients receiving insulin >2 weeks, as insulin antibody formation may occur
Semi-Quantitative Indirect Fluorescent Antibody
Useful to establish autoimmune etiology in previously diagnosed T1DM.
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Useful to establish autoimmune etiology in previously diagnosed T1DM.
See Related Tests
Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both. Type 1 DM (T1DM) is less common than type 2 DM (T2DM) and is characterized by insulin deficiency, often resulting from the autoimmune-mediated destruction of insulin-producing cells. The detection of diabetes-associated autoantibodies confirms an autoimmune etiology for that individual.
Indications for Insulin Antibody Testing
T1DM |
|
---|---|
T2DM | |
Screening |
Acceptable only for first-degree relatives of a proband with T1DM or in research settings |
Limited Use | |
GAD, glutamic acid decarboxylase antibody; IA-2, islet antigen-2; IAA, insulin antibody; ICA, islet cell cytoplasmic antibody; LADA, latent autoimmune diabetes of the adult; ZnT8, zinc transporter 8 antibody |
Diabetes Mellitus Type 1 Overview
Prevalence
1.25 million in the United States
Age of Onset
Most common in children but can develop in individuals of any age, especially in late 30s or early 40s
Symptoms
- Excessive thirst, hunger, and urination
- Fatigue, nausea, blurred vision
- Unexplained weight loss
- Obesity is rare upon initial diagnosis
- May have other autoimmune disorders
Physiology
- Caused by autoimmune-mediated destruction of insulin-producing beta cells of the islets of Langerhans in the pancreas
- Five major autoantibodies of diagnostic interest
- Glutamic acid decarboxylase (GAD)
- Insulin antibodies (IAA)
- Islet antigen-2 (IA-2)
- Islet-cell antibodies (ICA)
- Zinc transporter 8 (ZnT8)
- Antibodies may be present in individuals years before the onset of clinical symptoms
- Presence in individuals with diabetes confirms an autoimmune etiology
Test Interpretation
Sensitivity/Specificity
Moderate sensitivity, high specificity in newly diagnosed T1DM
- Presence of antibodies may decrease with long-term disease
- Insulin antibody testing loses specificity once patient has been on exogenous insulin for >2 weeks
Results
- Presence of multiple insulin antibodies (GAD, IA-2, IAA, ICA, and ZnT8) is predictive of T1DM
- If one autoantibody is found, others should be assayed; the risk of T1DM increases (>90%) if an individual tests positive for two or more autoantibodies
- For further risk stratification, HLA-DR or HLA-DQ genotyping may be helpful
Limitations
- Negative test results do not rule out autoimmune diabetes; autoantibody response varies by individuals
- Presence of a single autoantibody in the absence of clinical symptoms has low predictive value (1-2% in healthy individuals)
- Not all individuals with antibodies will develop T1DM
- Do not use to monitor or diagnose T1DM
- IAA test does not differentiate between antibodies specific for endogenous and exogenous forms of insulin
References
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Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974.
PubMed -
ADA - Standards of Medical Care in Diabetes--2020
American Diabetes Association. Standards of Medical Care in Diabetes--2020. Arlington County, VA. [Published: Jan 2020; Accessed: Mar 2020]
Online -
25869408
Handelsman Y, Bloomgarden ZT, Grunberger G , et al. American Association of Clinical Endocrinologists and American College of Endocrinology - Clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21 Suppl 1(Suppl 1):1‐87.
PubMed -
30565440
Pieralice S, Pozzilli P. Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management. Diabetes Metab J. 2018;42(6):451-464.
PubMed
NIH - Monogenic Diabetes: Neonatal Diabetes Mellitus & MODY
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Monogenic Diabetes (Neonatal Diabetes Mellitus & MODY). [Accessed: Apr 2020]
17519433
Nilsson C, Ursing D, et al. Presence of GAD antibodies during gestational diabetes mellitus predicts type 1 diabetes. Diabetes Care. 2007;30(8):1968-1971.
Use in combination with another insulin antibody test to determine autoimmune DM.