Table 3

Features influencing the pathogenesis and natural history of type 1 diabetes likely underappreciated in therapeutic trials seeking to prevent and or reverse the disease

ImmunePancreas/β-CellsEnvironment/Genetics
Innate immunitySmall pancreasMicrobiome (gut, oral)
Influence of age on immune responseVascular abnormalitiesDiet
Immune cell metabolismPancreatitis (role)Antibiotic use
Acute versus chronic β-cell destructionExocrine infiltrationExercise
Limited/focal nature of insulitisβ-Cell replication as a function of ageEpigenetic modifications Relationship with gut (including celiac disease)