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

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)