The American Diabetes Association supports using autoantibody (AAb) screening to diagnose T1D. T1D autoantibodies are markers of ongoing damage to insulin-producing beta cells. The four AAbs used in clinical practice to diagnose T1D are: AAbs against insulin (IAA), tyrosine phosphatase IA2 (IA2A), glutamic acid decarboxylase (GAD65), and zinc transporter. Numerous clinical trials demonstrate important clinical benefits associated with detecting T1D using an AAb screening approach.

Clinical guidelines have been established to help identify T1D at its earliest phases and before progression to DKA, providing presymptomatic and symptomatic staging of T1D.

Key clinical use and differentiators
Measurement of Glutamic acid decarboxylase (GAD65) is used to: 1. Screen for presymptomatic type 1 diabetes (T1D) in individuals with a family history of T1D or those known to have a high-risk HLA genotype, 2. Distinguish between T1D, type 2 diabetes mellitus (T2D), and atypical forms of diabetes such as latent autoimmune diabetes in adults (LADA). [1] Glutamic acid decarboxylase (GAD65) is a key protein that the immune system mistakenly attacks in people with T1D, and positivity to GAD65 antibodies represents a key marker of the disease. [1] GAD65 is the most common autoantibody found in adult-onset autoimmune diabetes. In addition to its importance in guiding the diagnosis of T1D, glutamic acid decarboxylase (GAD65) is also helpful to confirm the diagnosis of stiff-man syndrome, autoimmune encephalitis, autoimmune ataxia, brain stem encephalitis, autoimmune epilepsy, autoimmune myelopathy or pernicious anemia.

Intended Clinical Use
This test is crucial for differentiating between T1D and T2D. It is important to note that classifying diabetes type can be challenging at the time of presentation, and misdiagnosis can occur in approximately 40% of adults with new T1D. [1] Identifying individuals affected by stage 1 T1D is important for applying eligibility criteria to drugs, such as Teplizumab, which have demonstrated the ability to delay the transition of stage 1 to stage 3 T1D in clinical trials. [2,3] GAD65 has some distinctive features. It is commonly the first detected autoantibody in childhood, up until age 15 years. [4] Adult-onset T1D cases most often present with GADA. [5] It is associated with slower progression to T1D and is often found as a single positive islet autoantibody, especially in adults.

Limitations
T1D is classified into three stages, with stages 1 and 2 considered presymptomatic. Since the presence of stage 1 and 2 T1D requires at least two islet autoantibodies, relying solely on GAD65 as a screening test limits the ability to make an accurate diagnosis. Professional organizations, including the American Diabetes Association (ADA), recommend using tests for all four islet cell autoantibodies: IAA, glutamic acid decarboxylase (GAD65) Zinc Transporter 8 (ZnT8), and islet cell antigen 2 antibody (IA-2). [1]

References
1. American Diabetes Association Professional Practice C. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48:S27-S49. doi: 10.2337/dc25-S002
2. Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, Raymond R, Ramos EL. Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves beta-Cell Function. Diabetes Care. 2023;46:1848-1856. doi: 10.2337/dc23-0675
3. Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, et al. Teplizumab and beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389:2151-2161. doi: 10.1056/NEJMoa2308743
4. Krischer JP, Lynch KF, Schatz DA, Ilonen J, Lernmark A, Hagopian WA, Rewers MJ, She JX, Simell OG, Toppari J, et al. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015;58:980-987. doi: 10.1007/s00125-015- 3514-y
5. Leslie RD, Evans-Molina C, Freund-Brown J, Buzzetti R, Dabelea D, Gillespie KM, Goland R, Jones AG, Kacher M, Phillips LS, et al. Adult-Onset Type 1 Diabetes: Current Understanding and Challenges. Diabetes Care. 2021;44:2449- 2456. doi: 10.2337/dc21-0770

Key clinical use and differentiators
Measurement of Insulin Autoantibody (IAA) is used to: 1. Screen for presymptomatic type 1 diabetes (T1D) in individuals with a family history of T1D or those known to have a high-risk HLA genotype, 2. Distinguish between T1D, type 2 diabetes mellitus (T2D), and atypical forms of diabetes such as latent autoimmune diabetes in adults (LADA). [1] Insulin Autoantibody (IAA) is used to help predict the need for insulin treatment in adults with diabetes who have not received treatment with insulin. [1]

Intended Clinical Use
This test is crucial for differentiating between T1D and T2D. It is important to note that classifying diabetes type can be challenging at the time of presentation, and misdiagnosis can occur in approximately 40% of adults with new T1D. [1]

Identifying individuals affected by stage 1 T1D is important for applying eligibility criteria to drugs, such as Teplizumab, which have demonstrated the ability to delay the transition of stage 1 to stage 3 T1D in clinical trials [2,3]

IAA has some distinctive features, including that usually it is the first detected autoantibody in young children, [4] its appearance is more common in younger children [5] and its frequency of appearance declines with age. IAA is not informative for individuals treated with insulin, who often develop antibodies in response to injected insulin. [6]

Limitations
T1D is classified into three stages, with stages 1 and 2 considered presymptomatic. Since the presence of stage 1 and 2 T1D requires at least two islet autoantibodies, relying solely on IAA as a screening test limits the ability to make an accurate diagnosis. Professional organizations, including the American Diabetes Association (ADA), recommend using tests for all four islet cell autoantibodies: IAA, glutamic acid decarboxylase (GAD65), Zinc Transporter 8 (ZnT8), and islet cell antigen 2 antibody (IA-2).[1]

References
1. American Diabetes Association Professional Practice C. 2. Diagnosis and Classification of Diabetes: Standards of care in Diabetes-2025. Diabetes Care. 2025;48:S27-S49. doi: 10.2337/dc25-S002
2. Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, Raymond R, Ramos EL. Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves beta-Cell Function. Diabetes Care. 2023;46:1848-1856. doi: 10.2337/dc23-0675
3. Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, et al. Teplizumab and beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389:2151-2161. doi: 10.1056/NEJMoa2308743
4. Hummel S, Ziegler AG. Early determinants of type 1 diabetes: experience from the BABYDIAB and BABYDIET studies. Am J Clin Nutr. 2011;94:1821S-1823S. doi: 10.3945/ajcn.110. 000646
5. Ziegler AG, Bonifacio E, Group B-BS. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia. 2012;55:1937-1943. doi: 10.1007/ s00125-012-2472-x
6. Phillip M, Achenbach P, Addala A, Albanese-O'Neill A, Battelino T, Bell KJ, Besser REJ, Bonifacio E, Colhoun HM, Couper JJ, et al. Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care. 2024. doi: 10.2337/ dci24-0042

Key clinical use and differentiators
Measurement of Islet cell antigen 2 antibodies (IA-2) is used to: 1. Screen for presymptomatic T1D in individuals with a family history of type 1 diabetes (T1D) or those known to have a high-risk HLA genotype, 2. Distinguish between T1D, type 2 diabetes mellitus (T2D), and atypical forms of diabetes such as latent autoimmune diabetes in adults (LADA). [1] Positivity to IA-2 represents a key marker of T1D. [1]

Intended Clinical Use
This test is crucial for differentiating between T1D and T2D. It is important to note that classifying diabetes type can be challenging at the time of presentation, and misdiagnosis can occur in approximately 40% of adults with new T1D. [1]

Identifying individuals affected by stage 1 T1D is important for applying eligibility criteria to drugs, such as Teplizumab, which have demonstrated the ability to delay the transition of stage 1 to stage 3 T1D in clinical trials. [2,3]

IA-2 has some distinctive features. Its presence is associated with more-advanced islet autoimmunity and faster progression to stage 3 T1D. [4]

Limitations
T1D is classified into three stages, with stages 1 and 2 considered presymptomatic. Since the presence of stage 1 and 2 T1D requires at least two islet autoantibodies, relying solely on IA-2 as a screening test limits the ability to make an accurate diagnosis. Professional organizations, including the American Diabetes Association (ADA), recommend using tests for all four islet cell autoantibodies: IAA, glutamic acid decarboxylase (GAD65), Zinc Transporter 8 (ZnT8), and islet cell antigen 2 antibody (IA-2). [1]

References
1. American Diabetes Association Professional Practice C. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48:S27-S49. doi: 10.2337/dc25-S002
2. Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, Raymond R, Ramos EL. Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves beta-Cell Function. Diabetes Care. 2023;46:1848-1856. doi: 10.2337/dc23-0675
3. Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, et al. Teplizumab and beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389:2151-2161. doi: 10.1056/NEJMoa2308743
4. Decochez K, De Leeuw IH, Keymeulen B, Mathieu C, Rottiers R, Weets I, Vandemeulebroucke E, Truyen I, Kaufman L, Schuit FC, et al. IA-2 autoantibodies predict impending type 1 diabetes in siblings of patients. Diabetologia. 2002;45: 1658-1666. doi: 10.1007/s00125-002-0949-8

To assist with control of blood glucose levels, the American Diabetes Association (ADA) has recommended glycated hemoglobin testing (HbA1c) twice a year for patients with stable glycemia, and quarterly for patients with poor glucose control. Interpretative ranges are based on ADA guidelines.

Plasma glucose levels may be abnormally high (hyperglycemia) or abnormally low (hypoglycemia). Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolic disorders including diabetes mellitus, idiopathic hypoglycemia, and pancreatic islet cell neoplasm.

Key clinical use and differentiators
Measurement of Zinc transporter type 8 (ZnT8) is used to: 1. Screen for presymptomatic T1D in individuals with a family history of type 1 diabetes (T1D) or those known to have a high-risk HLA genotype, 2. Distinguish between T1D, type 2 diabetes mellitus (T2D), and atypical forms of diabetes such as latent autoimmune diabetes in adults (LADA).
Zinc transporter type 8 (ZnT8) is a transmembrane protein in the beta cell granule which is attacked by the ZnT8 antibody in patients with T1D.

Intended Clinical Use
This test is crucial for differentiating between T1D and T2D. It is important to note that classifying diabetes type can be challenging at the time of presentation, and misdiagnosis can occur in approximately 40% of adults with new T1D. [1]

Identifying individuals affected by stage 1 T1D is important for applying eligibility criteria to drugs, such as Teplizumab, which have demonstrated the ability to delay the transition of stage 1 to stage 3 T1D in clinical trials. [2,3]

ZnT8 has some distinctive features, including that its presence can improve risk stratification in individuals with single GADA+, IAA+ or IA-2A+ status. In one study, half of the children who developed ZnT8 developed diabetes within 5 years.[4]

Limitations
T1D is classified into three stages, with stages 1 and 2 considered presymptomatic. Since the presence of stage 1 and 2 T1D requires at least two islet autoantibodies, relying solely on ZnT8 as a screening test limits the ability to make an accurate diagnosis. Professional organizations, including the American Diabetes Association (ADA), recommend using tests for all four islet cell autoantibodies: IAA, glutamic acid decarboxylase (GAD65), Zinc Transporter 8 (ZnT8), and islet cell antigen 2 antibody (IA-2).[1]

References
1. American Diabetes Association Professional Practice C. 2. Diagnosis and Classification of Diabetes: Standards of care in Diabetes-2025. Diabetes Care. 2025;48:S27-S49. doi: 10.2337/dc25-S002
2. Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, Raymond R, Ramos EL. Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves beta-Cell Function. Diabetes Care. 2023;46:1848-1856. doi: 10.2337/dc23-0675
3. Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, et al. Teplizumab and beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389:2151-2161. doi: 10.1056/NEJMoa2308743
4. Achenbach P, Lampasona V, Landherr U, Koczwara K, Krause S, Grallert H, Winkler C, Pfluger M, Illig T, Bonifacio E, et al. Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia. 2009;52:1881-1888. doi: 10.1007/s00125-009-1438-0

This test is used for the routine diagnosis of diabetes in children and the non-pregnant adult. For pregnant females see test "Glucose Tolerance Test, Gestational, 4 Specimens (100 g)". For appropriate interpretation of this test, the patient must fast overnight and ingest a 75 g load of glucose, immediately after, a fasting specimen is obtained. For children, the glucose load is 1.75 g/Kg of ideal body weight, up to 75 g glucose. The diagnosis of diabetes is made if the fasting glucose is ≥126 mg/dL or if the 2-hour specimen is ≥200 mg/dL.