Insulin autoimmune syndrome in an Argentine woman taking α-lipoic acid: A case report and review of the literature

Insulin autoimmune syndrome is an unusual cause of spontaneous hypoglycaemia in non-Asian populations. In the majority of cases, this syndrome appears a few weeks after the administration of drugs containing a sulfhydryl group. A strong association between this syndrome and HLA-DR4 has been shown. Only seven cases have been described in non-Asian patients. We report the first case of insulin autoimmune syndrome in an Argentine woman taking alfa-lipoic acid. She developed hypoglycaemic symptoms approximately 1 month after starting therapy. Blood sampling collected during an episode of symptomatic hypoglycaemia showed low blood glucose level (2.39 mmol/L), high level of serum insulin (1971.55 pmol/L), inappropriately high level of C-peptide (2.36 nmol/L) and high levels of insulin antibodies (274.78 IU/mL). HLA-DNA typing identified DRB1*04:03. Due to the widespread use of alfa-lipoic acid for its antioxidant properties, clinicians should be aware that it may trigger an autoimmune hypoglycaemia in people with a genetic predisposition.

Download Full-text

Arare case of caucasian patient with insulin autoimmune syndrome induced by a-lipoic acid

Endocrine Abstracts ◽

10.1530/endoabs.70.aep360 ◽

2020 ◽

Author(s):

Spyridoula Glikofridi ◽

Labrini Papanastasiou ◽

Athina Markou ◽

Vasileios Andrianesis ◽

Christos Gravvanis ◽

...

Keyword(s):

Lipoic Acid ◽

Caucasian Patient ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome

Download Full-text

Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-18-0122 ◽

2018 ◽

Vol 2018 ◽

Cited By ~ 2

Author(s):

D Cappellani ◽

C Sardella ◽

M C Campopiano ◽

A Falorni ◽

P Marchetti ◽

...

Keyword(s):

Differential Diagnosis ◽

Lipoic Acid ◽

University Hospital ◽

Hypoglycaemic Episode ◽

List Type ◽

Alpha Lipoic Acid ◽

Previous Exposure ◽

Hyperinsulinaemic Hypoglycaemia ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome

Summary Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare hypoglycaemic disorder caused by the presence of high titer of insulin autoantibodies (IAA) in patients without previous exposure to exogenous insulin. Even though its pathogenesis is not fully understood, striking evidences link IAS to previous exposure to sulphydryl-containing medications, like alpha-lipoic acid, a widely used nutritional supplement. Although challenging, a careful differential diagnosis from other causes of hyperinsulinaemic hypoglycaemia (such as insulinoma) is mandatory, since these conditions require different therapeutic approaches. In the present study, we report a 35-year-old woman originally from Sri Lanka who was referred to our University Hospital on suspicion of occult insulinoma. Her medical history was positive for endometriosis, treated with estroprogestins and alpha-lipoic acid. The latter supplement was begun 2 weeks before the first hypoglycaemic episode. Our tests confirmed the presence of hypoglycaemia associated with high insulin and C-peptide concentrations. When insulin concentrations were compared using different assays, the results were significantly different. Moreover, insulin values significantly decreased after precipitation with polyethylene glycol. An assay for IAA proved positive (530 U/mL). A genetic analysis revealed the presence of HLA-DRB1*04,15, an immunogenetic determinant associated with IAS. On the basis of clinical data we avoided a first-line approach with immunosuppressive treatments, and the patient was advised to modify her diet, with the introduction of frequent low-caloric meals. During follow-up evaluations, glucose levels (registered trough a flash glucose monitoring system) resulted progressively more stable. IAA titer progressively decreased, being undetectable by the fifteenth month, thus indicating the remission of the IAS. Learning points: Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinaemic hypoglycaemia, whose prevalence is higher in East Asian populations due to the higher prevalence of specific immunogenetic determinants. Nevertheless, an increasing number of IAS cases is being reported worldwide, due to the wide diffusion of medications such as alpha-lipoic acid. Differential diagnosis of IAS from other causes of hyperinsulinemic hypoglycaemia is challenging. Even though many tests can be suggestive of IAS, the gold standard remains the detection of IAAs, despite that dedicated commercial kits are not widely available. The therapeutic approach to IAS is problematic. As a matter of fact IAS is often a self-remitting disease, but sometimes needs aggressive immunosuppression. The benefits and risks of any therapeutic choice should be carefully weighted and tailored on the single patient.

Download Full-text

Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-18-0011 ◽

2018 ◽

Vol 2018 ◽

Author(s):

A Veltroni ◽

G Zambon ◽

S Cingarlini ◽

M V Davì

Keyword(s):

Lipoic Acid ◽

Serum Insulin ◽

Strong Association ◽

High Serum ◽

List Type ◽

Alpha Lipoic Acid ◽

Hyperinsulinaemic Hypoglycaemia ◽

C Peptide ◽

Sulphydryl Groups ◽

Caucasian Patients

Summary Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Moreover, several recent reports showed a direct association between the onset of IAS and the consumption of dietary supplements containing alpha-lipoic acid (LA). Insulinoma remains the most prevalent cause of hypersulinaemic hypoglycaemia in Caucasians. Consequently, primary investigation in these patients is generally focused on localisation of the pancreatic tumour, often with invasive procedures followed by surgery. We described a case of an Italian woman presenting to us with severe recurrent hypoglycaemia associated with high insulin and C-peptide levels and no evidence of pancreatic lesions at imaging diagnostic procedures. She had taken LA until 2 weeks before hospitalisation. After an evaluation of her drug history, an autoimmune form of hypoglycaemia was suspected and the titre of insulin autoantibodies was found to be markedly elevated. This allowed us to diagnose LA-related IAS, thus preventing any unnecessary surgery and avoiding invasive diagnostic interventions. Learning points: IAS is a rare cause of hyperinsulinaemic hypoglycaemia that typically affects Asian population, but it has been increasingly recognised in Caucasian patients. It should be considered among the differential diagnosis of hyperinsulinaemic hypoglycaemia to avoid unnecessary diagnostic investigations and surgery. It should be suspected in the presence of very high serum insulin levels (100–10 000 μU/mL) associated with high C-peptide levels. There is a strong association with administration of drugs containing sulphydryl groups included LA, a dietary supplement commonly used in Western countries to treat peripheral neuropathy.

Download Full-text

The Novel Agent, Alpha Lipoic Acid, can Cause the Development of Insulin Autoimmune Syndrome

Internal Medicine ◽

10.2169/internalmedicine.46.0221 ◽

2007 ◽

Vol 46 (17) ◽

pp. 1321-1322 ◽

Cited By ~ 14

Author(s):

Yasuko Uchigata

Keyword(s):

Lipoic Acid ◽

The Novel ◽

Alpha Lipoic Acid ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Novel Agent

Download Full-text

Comparison of Two Autoimmune Dysglycemia Syndromes: Insulin Autoimmune Syndrome (IAS) and Type B Insulin Resistance Syndrome (B-IRS)

Hormone and Metabolic Research ◽

10.1055/a-1005-0071 ◽

2019 ◽

Vol 51 (11) ◽

pp. 723-728 ◽

Cited By ~ 1

Author(s):

Sui Yu ◽

Guoqing Yang ◽

Jingtao Dou ◽

Baoan Wang ◽

Weijun Gu ◽

...

Keyword(s):

Insulin Resistance ◽

Serum Insulin ◽

Insulin Resistance Syndrome ◽

Tolerance Test ◽

White Blood Count ◽

Oral Glucose ◽

Type B ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Clinical Differential Diagnosis

AbstractInsulin autoimmune syndrome (IAS) and type B insulin resistance syndrome (B-IRS) are rare autoimmune dysglycemia syndromes, but their treatment and prognosis are different. This study aimed to provide a basis for the clinical differential diagnosis of IAS and B-IRS. This was a retrospective study of the medical records of all patients diagnosed with IAS or B-IRS between January 2006 and March 2018 at the Chinese PLA General Hospital. Demographic, clinical, biochemistry, treatment, and follow-up data were examined. There were several different biochemical parameters between IAS (n=13) and B-IRS (n=6): white blood count (WBC, 7.05±3.06 vs. 2.70±0.73×109/l, p=0.004), platelet (249±56.6 vs. 111±68.0×109/l, p<0.001), serum creatine (59.0±17.8 vs. 43.1±7.05 μmol/l, p=0.013), serum albumin (42.3±5.17 vs. 33.6±3.40 g/l, p=0.002), triglyceride (median, 1.33 (1.01, 1.93) vs. 0.56 (0.50, 0.79) mmol/l, p=0.002), plasma IgG (1183±201 vs. 1832±469 mg/ml, p=0.018), IgA (328±140 vs. 469±150 mg/ml, p=0.018), and C3 (128±23.4 vs. 45.3±13.5 mg/l, p<0.001). Fasting insulin in the IAS and B-IRS patients was high (299–4708 vs. 118–851 mU/l, p=0.106), and there was a difference in 2 h oral glucose tolerance test insulin (4217–8343 mU/l vs. 274–1143 mU/l, p=0.012). Glycated hemoglobin (HbA1c) in the B-IRS patients was higher than in IAS patients (114±14.4. vs. 40.6±8.89 mmol/mol, p<0.001). Serum insulin-like growth factor-1 (IGF-1) was lower in all B-IRS patients (25±0.00 vs. 132±52.7 ng/ml, p<0.001). Although IAS and B-IRS are autoimmune hyperinsulinemic dysglycemic syndromes, several clinical parameters (body mass index, HbA1c, WBC, platelet, albumin, triglyceride, IgG, C3, and IGF-1) are different between these two syndromes.

Download Full-text