Exogenous Insulin Antibody Syndrome in Patients with Type 2 Diabetes

Figures & data

Table 1 Laboratory Investigations of Case 1

Date, h	Date: 07/06/2020			Date: 03/08/2020			Date: 20/11/2020			Date: 24/08/2021
	IAA(++)			IAA(+)			IAA(+-)			IAA(-)
	Therapy			Therapy			Therapy			Therapy
	Acarbose 100mg-50mg-50mg			Acarbose 50mg-50mg-50mg			Acarbose 50mg-50mg-50mg			Acarbose 50mg-50mg-50mg
	Glucose	Insulin	C-peptide	Glucose	Insulin	C-peptide	Glucose	Insulin	C-peptide	Glucose	Insulin	C-peptide
	mmol/L	mIU/L	nmol/L	mmol/L	mIU/L	nmol/L	mmol/L	mIU/L	nmol/L	mmol/L	mIU/L	nmol/L
0	5.6	732.1	1.43	6.7	357	0.89	7.6	256	0.94	6.3	154	0.74
0.5	11.4	852	1.91	9.9	380	1.1	8.9	277	1.1	7.8	181	1.3
1	16.6	908	2.28	14.1	468	1.66	11.2	319	1.35	10.2	242	1.7
2	17.2	1420	3.16	13.2	723	2.69	10	352	1.54	8.5	248	1.85
3	8.9	1150	2.49	6.3	595	1.85	13.4	399	2.06	9.5	272	2.24

Figure 1 Glucose, insulin, and C-peptide in the OGTT of case 1 before and after treatment.

Table 2 Laboratory Investigations of Case 2

Date, h	Date: 11/09/2020			Date: 03/02/2021			Date: 17/06/2021
	IAA(++)			IAA(+)			IAA(+-)
	Therapy			Therapy			Therapy
	Glargine 18U+Acarbose 100mg tid			Glargine 10U+Acarbose 50mg tid			Degludec 8U+Acarbose 50mg tid
	Glucose	Insulin	C-peptide	Glucose	Insulin	C-peptide	Glucose	Insulin	C-peptide
	mmol/L	mIU/L	nmol/L	mmol/L	mIU/L	nmol/L	mmol/L	mIU/L	nmol/L
0	13.6	531	0.41	4.5	126	0.23	3.6	26.1	0.05
0.5	15.1	606	0.52	8.4	254	0.32	7.4	38.3	0.12
1	18	603	0.59	10.8	263	0.58	9.8	42.6	0.47
2	22.1	833	0.87	12.3	335	0.76	11.1	37.8	0.38
3	22.3	889	0.86	9.1	321	0.69	8.9	26.5	0.25

Figure 2 Glucose, insulin, and C-peptide in the OGTT of case 2 before and after treatment.

Table 3 List of Medications and HLA Typing of Patients Reported in Case Series

Patients	Age	Sex	BMI	History of DM	Cause	IAA	R-INS	HLA typing	Associated	Therapy
	Years	M/F	kg/m^2	Years			mIU/L		Autoimmune Diseases
Case 1	45	M	21.91	11	Aspart 30	3+	732.1	DRB1*0405	Rheumatoid arthritis	Not specified
Case 2	64	F	19.71	16	Aspart 30	3+	531	DRB1*0301	None	Oral prednisone 30 mg/day for 5 days
3	77	F	29.35	1	Aspart 30	2+	36.2	DRB1*0901	None	Not specified
4	16	M	22.84	3	Aspart 30	2+	520	DRB1*0901	Autoimmune thyroiditis	Not specified
5	68	M	22.14	12	Humulin 70/30	3+	>1000	DRB1*0405	None	Oral prednisone 30 mg/day for 7 days
6	51	F	32.04	19	Aspart 30	1+	41.4	DRB1*1202	None	Not specified
7	70	F	22.81	25	Aspart 30	1+	153	DRB1*0405	None	Not specified
8	73	M	20.4	16	Humulin 70/30	1+	63	DRB1*1202	None	Not specified
9	68	M	18.6	13	Detemir	2+	117	DRB1*0301	None	Not specified
10	66	M	27.99	10	Detemir+Aspart	3+	423	DRB1*0301	None	Not specified
11	58	M	23.53	18	Novolin 30R	3+	789	DRB1*0405	None	Not specified
12	44	F	17.48	5	Humulin 70/30	3+	532	DRB1*0803	None	Oral prednisone 30 mg/day for 7 days
13	75	M	20.96	16	Aspart 30	3+	646	DRB1*0701	None	Not specified
14	53	M	21.58	13	Lispro 25	2+	367	DRB1*0405	None	Not specified
15	40	F	22.75	9	Novolin 30R	3+	372	DRB1*0301	Autoimmune thyroiditis	Not specified
16	70	F	20.35	19	Lispro 25	2+	222	DRB1*1202	None	Not specified
17	56	M	24.88	6	Novolin 30R	2+	152	DRB1*0901	None	Not specified

Table 4 General Data and Clinical Information of Patients Reported in Case Series

Parameter		Value
Age	Years	58.47±15.79
Sex	Male	58.82%
Course of diabetes	Years	12.47±6.37
BMI	kg/m^2	22.90±3.81
HbA1c	%	7.7±0.4
Indication for insulin	T1DM	5.88%
	T2DM	94.10%
	LADA	/
Concomitant sulfhydryl drugs	Glutathione	23.50%
Concomitant autoimmune diseases	Grave’s diseases, Hashimoto’s thyroiditis, rheumatoid arthritis	11.70%
Insulin dosage	IU/day	22.32±1.31
Duration of insulin use	Months	11.51±1.86
Insulin types	Recombinant human insulin	/
	Short-acting insulin	/
	Neutral protamine Hagedorn	/
	Insulin analogue
	Aspart	5.88%
	Glargine	/
	Lispro	/
	Detemir	11.76%
	Degludec	/
	Premixed insulin
	Premixed human insulin
	Novolin 30R	11.76%
	Humulin 70/30	11.76%
	Premixed insulin analogues
	Aspart 30	41.17%
	Lispro 25	11.76%
Clinical manifestations	Hypoglycemia	41.17%
	Autonomic nervous system: palpitations, sweating, hunger and hand tremors	11.76%
	Neurological hypoglycemia: dizziness	/
	No symptoms of hypoglycemia	11.76%
	Nocturnal hypoglycemia along with daytime hyperglycemia	17.64%
Insulin (mIU/L)	Fasting insulin levels
	24.9–100	17.60%
	100–300	23.52%
	300–1000	53%
	>1000	6%
Antibody
IAA	Positive	100%
ICA	Positive	11.76%
GAD	Positive	5.88%
Allelic genes	DRB1*04:05:01	29%
	DRB1*03:01:01	23.53%
	DRB1*09:01:02	17.64%
	DRB1*12:02:01	17.64%
	DRB1*08:03:02	5.88%
	DRB1*07:01:01	5.88%
Blood lipid
	Total cholesterol (mmol/L)	6.57±1.12
	Triglycerides (mmol/L)	2.62±0.85
	HDL cholesterol (mmol/L)	1.12±0.53
	LDL cholesterol (mmol/L)	4.57±0.67
	Free fatty acid (mmol/L)
Index of inflammatory
	HS-CRP (ng/L) (<3ng/L)	0.55±0.14
	IL-6 (pg/mL) (<7pg/mL)	4.05±1.42
	PCT (ng/mL) (<0.046ng/mL)	0.021±0.65
Index of bone metabolism
	PTH (ng/L) (15–65ng/L)	48.46±2.37
	25-OH-VD (ng/mL) (≥20ng/mL)	12.60±0.94
	N-MID (ng/mL) (15–46ng/mL)	10.08±0.75
	B-CTX (ng/mL) (<1.008ng/mL)	0.37±0.12
	CT (pg/mL) (<6.4pg/mL)	0.53±0.13
	TPINP (ng/mL) (15.13–58.19ng/mL)	56.68±6.37