GAD-65

Laboratory assay overview

Diabetes autoantibodies assessment is helpful in identifying and managing patients at risk for development of type 1 diabetes. Published positivity rates for diabetes autoantibodies in new-onset type 1 diabetes patients listed below are based on the combined analysis of GAD-65, ICA 512, insulin antibodies, and ZnT8 antibodies. The combined analysis has a 98% autoimmunity detection rate, with 1.8% diabetic individuals remaining as autoantibody-negative. fewer than 3% of type 2 diabetics have positive antibodies.1 Positive rate in new-onset type 1 diabetes patients: • GAD-65 antibodies = 68% positive • ICA 512 antibodies = 72% positive • Insulin antibodies = 55% positive • ZnT8 antibodies = 63% positive An increase in the number of positive antibodies is associated with a higher likelihood of type 1 diabetes.

Laboratory assay overview

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.

Quest Diagnostics population reference ranges

Quest Diagnostics calculates these statistical intervals for this specific assay and demographic group, not as universal optimal targets.

Laboratory assay overview

This test is intended for the semiquantitative determination of glutamic acid decarboxylase (GAD) antibody in human serum; it is useful as an aid in the diagnosis of type 1 diabetes mellitus (autoimmune mediated diabetes).1

Laboratory assay overview

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