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Objective Type 1 diabetes (T1D) is known to be caused by Th1 cell-dependent autoimmunity. Recently, we reported that TYK2 promoter variant serves as a putative virus-induced diabetes susceptibility gene associated with deteriorated interferon-dependent antiviral response. TYK2 is also related to HIES, that is, Th2 cell-dependent. Therefore, TYK2 promoter variant may be also associated with the pathogenesis of T1D, modulating Th1/Th2 balance. Research Design and Methods We assessed the association between anti- GAD Ab, IgE levels, and TYK2 promoter variant among 313 T1D patients, 184 T2D patients, and 264 YH controls in the Japanese. Results T1D patients had elevated IgE (median, 56.7 U/ml; p, Highlights • T1D can be subtyped into 4 groups based on anti-GAD Ab, IgE levels and TYK2 promoter variant. • Only one subtype, without anti-GAD Ab or elevated IgE, was associated with TYK2 promoter variant and flu-like syndrome. • Profiling of T1D by anti-GAD Ab and IgE levels is useful to realize the variable immuno-pathogenesis of T1D. Since TYK2 gene is associated with T1D and HIES, we assessed the association between anti-GAD Ab, IgE levels, and TYK2 promoter variant in patients with T1D. Consequently, T1D can be subtyped into 4 distinct groups based on these clinical laboratory and genetic markers. Only those patients without anti-GAD Ab or elevated IgE were associated with TYK2 promoter variant and with flu-like syndrome at the diabetes onset, suggestive of association with virus-induced diabetes. This study describes the usefulness of subtyping of T1D with variable immunological bases and provides a clue to delineate the pathogenesis of T1D.