Background Since their recent discovery of zinc transporter 8 antibodies (ZnT8A) by Wenzlau et al. in 2007, the relevance and clinical utility of this marker has been in question. Some recent reports have shown a wide potential for both diagnostic as well as prognostic clinical applications in T1DM as they can be found years before clinical symptoms appear. Understanding the timing of the seropositivity of antibodies such as ZnT8A can help us understand how to utilize this marker for the diagnosis and prognosis of T1DM. Up to 20% of T1DM patients are reported to have ZnT8A positive with negative GAD-65 and IAA autoantibodies. The duration of seropositivity of ZnT8A is unclear. We describe 2 cases from our endocrine clinic with significant zinc 8 transporter antibody titers over 8 - 26 years after their initial diagnosis. Clinical Cases CASE 1: 34-year-old man diagnosed initially with T2DM 9 years prior and later re-classified as T1DM. He was treated initially with oral agents and switched over to Multiple Daily Injection (MDI) insulin about 3-4 years later. He has no family history of diabetes. Approximately 8 years after his initial diagnosis, his autoantibodies profile showed a positive zinc transporter 8 antibody of 28 U/mL (reference of < 15 U/mL), but negative GAD-65 antibodies (reference <5 IU/mL) and negative Islet cell antibodies. CASE 2: 47-year-old man diagnosed with T2DM in 1995 and was initially started on oral hypoglycemic medications. He was later evaluated at our endocrinology clinic and reclassified as type 1 DM after his serologic testing showed a low C peptide < 0.1 ng/mL, positive zinc transporter 8 antibody of 32 U/mL (reference of < 15 U/mL), and negative islet cell antibody screen negative, and negative GAD-65 antibodies (reference <5 IU/mL). He was transitioned to continuous glucose monitoring and an insulin pump, but was too difficult for the patient to manage. He was ultimately transitioned to a basal-bolus regimen of insulin with MDI. His latest serologic testing showed a HgA1C of 9.2%. Conclusions Zinc 8 transporter antibody can help differentiate type 1 from type 2 diabetes and initiate insulin therapy for better glycemic control as well as aid in prognosis and stratification strategies. The duration of seropositivity of ZnT8A has not been clearly established. Previous reports have shown that ZnT8A can be detected at an age around 3 years of age, but peaks around late adolescence and does not have a significant decline in seropositivity rates in older adults, as does IAA. This emphasizes the use of ZnT8A as a useful marker in adult and elderly patients. We describe 2 case reports which indicate that ZnT8 antibodies can remain positive for at least 8 - 26 years in the absence of other autoantibodies. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.