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Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α‐lipoic acid
Author(s) -
Gullo Damiano,
Evans Joseph L.,
Sortino Grazia,
Goldfine Ira D.,
Vigneri Riccardo
Publication year - 2014
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12334
Subject(s) - medicine , insulin , endocrinology , allele , prednisone , discontinuation , autoantibody , lipoic acid , human leukocyte antigen , disease , diabetes mellitus , immunology , antigen , biology , antibody , genetics , biochemistry , gene , antioxidant
Summary Objective Lipoic acid ( LA ) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome ( IAS , Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen ( HLA ) HLA‐DRB 1*04:06 allele and often occurs upon exposure to sulphhydryl‐containing compounds including LA . Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients. Research Design and Methods Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid ( LA ; 600 mg/day). Case histories and standard laboratory analyses were utilized. Results Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12·5–25 mg/day). HLA analysis revealed the HLA‐DRB 1*04:03 allele in five patients, while the HLA‐DRB 1*04:06 allele was present in one patient. Conclusions This is the first report of LA ‐related IAS in Caucasians who possess the HLA ‐ DRB 1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in C aucasians. The greater occurrence of the HLA‐DRB 1*04:03 allele in C aucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS .