Possible Relevance of HLA-DRB1*0403 Haplotype in Insulin Autoimmune Syndrome Induced by α-Lipoic Acid, Used as a Dietary Supplement
- Tetsuya Yamada, MD, PHD,
- Junta Imai, MD, PHD,
- Yasushi Ishigaki, MD, PHD,
- Yoshinori Hinokio, MD, PHD,
- Yoshitomo Oka, MD, PHD and
- Hideki Katagiri, MD, PHD
- Address correspondence to Dr. Hideki Katagiri, Department of Diabetes and Metabolism, Tohoku University Hospital, Seiryo, Aoba, Sendai, 980-8575, Japan. E-mail: katagiri{at}mail.tains.tohoku.ac.jp
Insulin autoimmune syndrome (IAS) is characterized by frequent hypoglycemic attacks associated with the presence of autoantibodies to insulin in patients who have not received insulin injections. Approximately half of IAS patients have a medication history before onset, and over 90% of the agents are sulfydryl compounds such as methimazole, mercaptopropionyl glycine, or glutathione. In addition to these compounds, α-lipoic acid (ALA), which is widely used as a health supplement, is associated with a risk of IAS induction, as previously reported in Diabetes Care (1) and other journals (2,3). DRB1*0406 is reportedly the most common and DRB1*0403 the next most common HLA haplotype conferring susceptibility to IAS (4). As for ALA-induced IAS, all three reported cases have the DRB1*0406 but not the DRB1*0403 haplotype (1–3). However, we recently observed a case of IAS, possibly induced by ALA, in a patient who has the DRB1*0403 haplotype.
The patient, a 45-year-old woman, lapsed into hypoglycemic coma 1 month after starting to take ALA. She had not taken any of the other aforementioned sulfydryl compounds. She exhibited marked hyperinsulinemia (fasting plasma glucose 88 mg/dl, serum immunoreactive insulin 13,240 μU/ml, and serum C-peptide immunoreactivity 2.93 ng/ml). Antibodies to insulin were detected with an insulin binding ratio of 81.2%. Antibody affinity was low, while binding activity was high, as commonly observed in IAS. Based on these results, she was diagnosed as having IAS possibly induced by ALA. However, she has the DRB1*0403, not the DRB1*0406, haplotype.
This is the first report of a patient with ALA-induced IAS having the DRB1*0403 haplotype. Since the DRB1*0403 haplotype is reportedly associated with IAS induced by other sulfydryl compounds, it is likely to confer susceptibility to ALA-induced IAS. Although IAS was a relatively rare cause of hypoglycemia in the past, ALA has become more widely available as a dietary supplement for treating obesity and diabetes complications. Furthermore, in contrast to the very low prevalence of DRB1*0406 in ethnic groups other than East Asians, DRB1*0403 was found to be widely distributed across various populations (5). We should therefore be more aware of ALA-induced IAS.
