Recent advances in genetic research have led to the identification of over sixty loci that contribute to the susceptibility of developing Type 1 diabetes (T1D). The plethora of T1D risk genetic variants that has been identified may be overwhelming for clinicians faced with lists of gene names and symbols that have little bearing on management; it also provides a challenge for researchers to identify the mechanism by which these variants contribute to disease, and to place the genetics of T1D in a more amenable clinical context We examined the genetic data from 3,348 T1D subjects and produced evidence that defined six disease subtypes based on genotypes at HLA and 19 non-HLA loci. Validation demonstrated that affected siblings were highly likely to share the same T1D subtype, consistent with a genetic basis for each subtype. The T1D subtypes differed significantly in all clinical features examined, including age at diagnosis, autoantibody status and presence of other autoimmune diseases. Definition of T1D subtypes may allow better characterization, prevention and clinical management of this disease.