Redondo MJ, Sosenko J, Libman I, et al. - As clinical (stage 3) type 1 diabetes (T1D) is preceded by multiple islet autoantibody positivity, researchers examined if individuals who develop stage 3 T1D with only a single autoantibody have unique metabolic differences. They conducted a cross-sectional analysis of participants in the T1D TrialNet study. Participants were autoantibody-positive relatives who developed stage 3 T1D (at median age 12.4 years, range = 1.4-58.6) and had autoantibody data close to clinical diagnosis (n = 786, 47.4% male, 79.9% non-Hispanic White). At the diagnosis of stage 3 T1D, 119 (15.1%) participants exhibited single autoantibody positivity. Compared with multiple autoantibody positivity, single autoantibody at diagnosis of stage 3 T1D was correlated with older age and insulin resistance. Elevated BMI likely mediates this correlation, implying heterogeneous disease pathogenesis. These variations are potentially important for T1D prevention and treatment.