Endocrinol Metab.  2013 Dec;28(4):326-330. 10.3803/EnM.2013.28.4.326.

Recurrent Insulin Autoimmune Syndrome Caused by alpha-Lipoic Acid in Type 2 Diabetes

• Bae SM
• Bae MN
• Kim EY
• Kim IK
• Seo MW
• Shin JK
• Cho SR
• Jeong GH

• KMID: 2169311
• DOI: http://doi.org/10.3803/EnM.2013.28.4.326

Abstract

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed alpha-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

Keyword

Alpha-lipoic acid; HLA-DRB1*0406 antigen; Insulin antibodies; Insulin autoimmune syndrome

MeSH Terms

Aged
Alleles
Ambulatory Care Facilities
Autoantibodies
Diabetic Neuropathies
Female
Genotype
Humans
Hypoglycemia
Insulin Antibodies
Insulin*
Leukocytes
Polyneuropathies
Prednisolone
Sulfhydryl Compounds
Sulfur
Thioctic Acid*
Autoantibodies
Insulin
Insulin Antibodies
Prednisolone
Sulfhydryl Compounds
Sulfur
Thioctic Acid

Figure

• 

  Fig. 1 Abdominal computed tomography shows no abnormal lesion in the pancreas.

Reference

1. Hirata Y, Ishizu H, Ouchi N, Motomura S, Abe M, Hara Y, Wakasugi H, Takahashi I, Sakano H, Tanaka M, Kawano H, Kanesaki T. Insulin autoimmunity in a case of spontaneous hypoglycemia. J Jpn Diabetes Soc. 1970; 13:312–320.

2. Uchigata Y, Hirata Y, Iwamoto Y. Drug-induced insulin autoimmune syndrome. Diabetes Res Clin Pract. 2009; 83:e19–e20.

3. Chang HJ, Choi HS, Park MY, Leem SM, Jang YS, Park KS, Lee JM. A case of insulin autoimmune syndrome related to alpha-lipoic acid. Korean J Med. 2009; 76:600–604.

4. Kim MJ, Shin MS, Kim MK, Lee Y, Kim YU, Shin YG, Chung CH. A case of autoimmune hypoglycemia induced by insulin autoantibody and insulin receptor autoantibody. Diabetes Monit. 2002; 3:177–184.

5. Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin autoimmune syndrome possibly caused by alpha lipoic acid. Intern Med. 2007; 46:237–239.

6. Uchigata Y, Kuwata S, Tokunaga K, Eguchi Y, Takayama-Hasumi S, Miyamoto M, Omori Y, Juji T, Hirata Y. Strong association of insulin autoimmune syndrome with HLA-DR4. Lancet. 1992; 339:393–394.

7. Uchigata Y. The novel agent, alpha lipoic acid, can cause the development of insulin autoimmune syndrome. Intern Med. 2007; 46:1321–1322.

8. Uchigata Y, Hirata Y, Iwamoto Y. Insulin autoimmune syndrome (Hirata disease): epidemiology in Asia, including Japan. Diabetol Int. 2010; 1:21–25.

9. Bresciani E, Bussi A, Bazzigaluppi E, Balestrieri G. Insulin autoimmune syndrome induced by alpha-lipoic acid in a Caucasian woman: case report. Diabetes Care. 2011; 34:e146.

10. Dozio N, Scavini M, Beretta A, Sarugeri E, Sartori S, Belloni C, Dosio F, Savi A, Fazio F, Sodoyez JC, Pozza G. Imaging of the buffering effect of insulin antibodies in the autoimmune hypoglycemic syndrome. J Clin Endocrinol Metab. 1998; 83:643–648.