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We aimed to assess the impact of routine islet autoantibody testing in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide\u2013to\u2013creatinine ratio [UCPCR]) in 722 adults (\u226518 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration &amp;lt;12 months. We also evaluated changes in treatment and glycemia over 2 years after informing participants and their clinicians of autoantibody results.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Of 722 participants diagnosed with type 1 diabetes, 24.8% (179) were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of nonautoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative vs. positive: 10.85 vs. 13.09 [P &amp;lt; 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), \u221224% vs. \u221243% (P &amp;lt; 0.001).<\/jats:p><jats:p>After median 24 months of follow-up, treatment change occurred in 36.6% (60 of 164) of autoantibody-negative participants: 22.6% (37 of 164) discontinued insulin, with HbA1c similar to that of participants continuing insulin (57.5 vs. 60.8 mmol\/mol [7.4 vs. 7.7%], P = 0.4), and 14.0% (23 of 164) added adjuvant agents to insulin.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured, negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc22-0623","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T14:17:32Z","timestamp":1665152252000},"page":"2844-2851","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation"],"prefix":"10.2337","volume":"45","author":[{"given":"Russell J.","family":"Eason","sequence":"first","affiliation":[{"name":"1University of Exeter College of Medicine & Health, Exeter, U.K."},{"name":"2Royal Devon University Healthcare NHS Foundation Trust, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas 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