Table 1.

Comparison of the disease phenotype of checkpoint inhibitor associated autoimmune diabetes (CIADM) to traditional type 1 diabetes (T1D).

	CIADM	T1D
Presentation	DKA in 67.5% at presentation (55). 47.5% have a comorbid irAE, most common being thyroid (24.5%) (55).	DKA in 39% children at presentation (104), 6% in adults (105)
Clinical course	Fulminant presentation, median 9 weeks after ICI treatment	Progressive development of islet autoantibodies → overt hyperglycaemia at presentation
	No spontaneous remission phase or “honeymooning”. Overt insulin deficiency and low C-peptide at presentation in most (<0.3ng/ml in 63.4%) (55)	‘Honeymooning’ in 68.9% of children with T1D with partial recovery of β-cell function (106)
		Progressive decline in C-peptide, 48% maintain stimulated C-peptide >0.2nmol/L at 5 years (107)
Autoantibodies	Anti-GAD autoantibodies + in 43% (overall islet autoantibody positivity 20-71%) (55).	Islet autoantibodies + in 90% (40)
Genetic predisposition	65.4% with T1D susceptibility haplotype, 10.3% with T1D protective haplotype (55)	T1D susceptible haplotypes in 90% (80)
Exocrine pancreas involvement	Pancreatic enzymes elevated in 51% (55), pancreatic atrophy on imaging (54, 95)	Lower lipase vs normal controls except in fulminant phenotype (86), reduced pancreatic volumes (83–85)
Proposed pathophysiology	Prior exposure to environmental trigger leading to islet specific autoimmunity, tolerised by PD-L1	Genetic predisposed individual exposed to an environmental trigger, leading to autoimmune β-cell destruction
	Exposure to anti-PD1 or anti-PD-L1 unmasks autoimmunity and triggers β-cell destruction

DKA, diabetic ketoacidosis; irAE, immune related adverse event.