Exogenous insulin-associated autoimmunity and the emergence of double diabetes in type 2 diabetes

Table 1 Clinical, biochemical, and genotypic characteristics of the 23 cases

	Ethnicity	Sex/age (year)	Insulin preparation	Duration of insulin use (month)	Duration since initial diagnosis (year)	ICA	IA-2A	GADA	IAA-pre insulin	IAA titer	IAA detection method	Insulin allergy	Lipoatrophy	Hypoglycemia	DKA	C-P (pre) (pmol/L)	C-P (post) (pmol/L)	Treatment	DRB1	DQB1
Case 1	Chinese	F/49	NR, L	1	NA	-	-	-	-	NA	CL	+	+	+	+	329.7	< 30	NA	04:05 15:01	04:01 04:01
Case 2	Japanese	M/70	N	5	30	-	-	+	NA	13	RI	+	NA	+	+	560	< 16.65	NR	04:05 09:01	04:01 03:03
Case 3	Japanese	M/50	A, M30	2	5	+	+	+	NA	12	RI	+	NA	-	-	370	33.3	NU, H	09:01 08:03	03:03 03:01
Case 4	Japanese	M/69	H70/30	2	20	-	-	-	NA	14	RI	-	NA	-	-	900	33.3	H, HN	04:05 04:05	04:01 04:01
Case 5	Japanese	M/63	M30	17	29	-	-	-	NA	2	RI	-	NA	NA	-	NA	< 30	NA	09:01 01:01	03:03 05:01
Case 6	Japanese	F/67	R, H70/30	7	15	-	-	-	NA	9	RI	+	NA	NA	-	NA	< 30	NA	04:05 14:07	04:01 05:02
Case 7	Japanese	F/38	N, NR	13	2	+	NA	+	NA	7	RI	-	NA	NA	-	NA	NA	NA	09:01 09:01	03:03 03:03
Case 8	Chinese	F/25	NR, D	0.5	1	-	-	-	NA	75	RI	+	-	-	+	NA	8	NR, DG	04:05	04:01
Case 9	Japanese	M/75	R, N	12	20	+	+	+	NA	9	RI	-	+	+	-	NA	< 30	Pred	04:05 13:02	04:01 06:04
Case 10	Chinese	F/65	A	6	10	-	-	-	NA	125#	RI	-	NA	-	+	NA	50	Pred	04:03	NA
Case 11	Chinese	M/53	GI	30	8.4	-	-	-	NA	256	CL	NA	+	NA	NA	NA	NA	NA	02:01 03:02	04:03 07:01
Case 12	Chinese	F/24	GI	2	1.4	NA	NA	NA	NA	7.82	CL	NA	NA	NA	NA	NA	NA	NA	03:01 03:02	04:06 11:01
Case 13	Chinese	M/55	H3/7	18	2.2	-	-	-	NA	390	CL	NA	NA	NA	NA	NA	NA	NA	03:01 03:01	12:01 12:02
Case 14	Chinese	F/50	GI	0.5	11.1	-	-	-	NA	691.5	CL	+	NA	NA	NA	NA	NA	NA	03:02 03:02	04:06 04:06
Case 15	Japanese	M/66	H3/7	12	27	NA	-	-	NA	20	RI	+	NA	+	NA	NA	0.47	Liraglutide, voglibose, mitiglinide	04:01 04:06	03:02 05:01
Case 16	Japanese	M/46	NR	12	NA	NA	NA	NA	NA	13.6	RI	NA	NA	+	NA	NA	0.40	Nateglinide	09:01 15:02	03:03 06:01
Case 17	Chinese	M/49	N30R	12	10	NA	NA	NA	NA	NA	RI	NA	NA	+	NA	NA	1.43	Acarbose	04:05	NA
Case 18	Japanese	M/86	NA	20	NA	NA	NA	NA	NA	20.9	RI	NA	NA	+	NA	NA	NA	Cyclophosphamidepulse and Preds	04:06	NA
Case 19	Japanese	M/83	NA	15	NA	NA	NA	NA	NA	22.4	RI	NA	NA	+	NA	NA	NA	DFPP and Preds	08:03 09:01	NA
Case 20	Japanese	F/60	R	21	NA	NA	NA	+	NA	10	RI	NA	NA	+	NA	NA	NA	NA	04:05 09:01	NA
Case 21	Japanese	F/69	M30	20	NA	NA	NA	-	NA	13	RI	NA	NA	+	NA	NA	NA	NA	08:03 09:01	NA
Case 22	Japanese	F/60	M30	2	NA	NA	NA	-	NA	14	RI	NA	NA	+	NA	NA	NA	NA	04:05 14:01	NA
Case 23	Chinese	M/83	N, GI	20	NA	-	-	NA	NA	14	NA	NA	NA	+	NA	NA	1.19	Linagliptin	08:03 12:02	NA

Cases 1-10 belong to the T2D→T1D group, while Cases 11-23 comprise the T2D→T2D group. Demographic data, insulin formulations, duration of insulin therapy, time since initial diabetes diagnosis, autoantibody profiles-including changes in insulin autoantibodies and their titers-as well as DRB1 and DQB1 genotypes, are summarized. In addition, key clinical outcomes-including insulin allergy, lipoatrophy, hypoglycemia, and diabetic ketoacidosis-alongside biochemical indicators such as pre- and post-treatment C-peptide levels, are also presented. GADA: Glutamic acid decarboxylase antibodies; IAA: Insulin autoantibodies; ICA: Islet cell antibodies; DKA: Diabetic ketoacidosis.