Table 1.

Stages in the pathogenesis of type 1 diabetes¹⁹

Nomeclature	Prestage 1	Stage 1	Stage 2	Stage 3
Natural history	Genetic and environmental susceptibility	Presymptomatic	Presymptomatic	Symptomatic
β cell autoimmunity	0–1 autoantibodiesa	2 or more autoantibodiesb	2 or more autoantibodiesb	2 or more autoantibodiesb
Glucose tolerance and glycemia	Normal, normoglycemia	Normal, normoglycemia	Impaired, dysglycemia	Diabetic, dysglycemia
First-phase insulin response	Normal	Normal to mild impairment	Impaired	Absent
β cell secretory capacity	Normal	Normal to moderate impairment	Variable impairment	Markedly impaired to absent

^aT1D-associated autoantibodies include those against the β cell–specific antigens, glutamic acid decarboxylase 65 (GAD-65), the tyrosine phosphatase–related islet antigen 2 (IA-2), insulin (IAA), and zinc transporter 8 (ZnT8).

^bThe risk for disease progression toward diabetes is much less with a single autoantibody; however, some individuals with a single autoantibody do progress, and the clinical diagnosis of symptomatic T1D does not require the presence of multiple autoantibodies.