Differences in Clinical Manifestations and Islet Autoantibodies by Age in Adult-Onset Type 1 Diabetes.

Karakus, Kagan E; Clayton, Maia G; Baschal, Erin E; McDaniel, Kristen A; Yu, Liping; Haider, Zehra; Polsky, Sarit; Akturk, Halis K et al. · Diabetes Care · 2026

retrospective_cohort · Level III

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Abstract

Adult-onset type 1 diabetes is not well characterized, especially after 40 years of age, and is commonly misdiagnosed as type 2 diabetes. We evaluated the differences in clinical presentation, islet autoantibodies, and HLA genetics between pediatric- and adult-onset type 1 diabetes. Individuals who were newly diagnosed with type 1 diabetes were tested for islet autoantibodies within 1 year of diagnosis in this retrospective study. Islet autoantibodies against GAD, insulin, islet antigen 2, and zinc transporter 8 were measured using fluid-phase radiobinding assays. High-resolution HLA class I (n = 655) and II (n = 1,196) typing was performed in a subset of participants. In total, 414 adults (aged ≥20 years) and 2,000 children were included. Adults were aged 20 to 76 years and had a mean BMI of 23.5 ± 4.7 kg/m2 at onset. Compared with children, adults presented with diabetic ketoacidosis (DKA) less frequently (32.6% vs. 56.0%; P < 0.001) and with slightly lower HbA1c values (11.3% ± 2.6% vs. 12.0% ± 2.4%; P < 0.001). Notably, adults older than 40 years (n = 84) presented with DKA only 13.1% of the time. Adults more often presented with zero or one islet autoantibodies compared with children (43.0% vs. 20.2%; P < 0.001). There were no differences in high-risk HLA haplotypes between adults and children (DR4-DQ8: 57.1% vs. 63.7%; P = 0.060; DR3-DQ2: 43.6% vs. 46.1%; P = 0.482). Adult-onset type 1 diabetes is characterized by a reduced frequency of DKA and by fewer total islet autoantibodies. Our findings can help in the accurate diagnosis of type 1 diabetes in adults.