Insulin Autoimmune Syndrome: A Case of Clopidogrel-induced Autoimmune Hypoglycemia

Abstract

Context Insulin autoimmune syndrome (IAS) is characterized by hyperinsulinemic hypoglycemia with elevated anti-insulin antibodies. Most commonly observed in the Japanese population, elsewhere it is rare and associated with autoimmune diseases, plasma cell dyscrasias, or sulfhydryl group medications. The active metabolite of clopidogrel has a sulfhydryl group and here we report a case of clopidogrel-induced IAS. Case Description A 67-year-old man was admitted with severe hyperinsulinemic hypoglycemia requiring continuous intravenous infusion of 10% dextrose to sustain euglycemia. His symptoms of hypoglycemia had started after commencing dual antiplatelet therapy (including clopidogrel) for ischemic heart disease 9 months earlier. The hypoglycemia was associated with elevated insulin, proinsulin, c-peptide, and anti-insulin antibody titers as well as the HLA-DRB1*04 haplotype. Multiple localizing studies were negative for an insulinoma. A diagnosis of IAS was thus made. Clopidogrel cessation, oral dexamethasone, and diazoxide therapy were not sufficient to safely wean the dextrose infusion. Plasma exchange was ultimately effective. Conclusions This case highlights a case of severe IAS. Given the ubiquity of clopidogrel, IAS should be remembered as a rare adverse effect.

Case Report: Recurrent Autoimmune Hypoglycemia Induced by Non-Hypoglycemic Medications

“…The top three drugs were methimazole, alipoic acid, and tiopronin (24). Clopidogrel was the fifth most common drug if adding our case (5,17,18,(24)(25)(26). Moreover, 11 of the 134 AIH cases with unknown causes were considered to have been caused by clopidogrel tablets, as each of these patients had a history of exposure to clopidogrel or a history of coronary heart disease or coronary or carotid artery stent implantation (19,(27)(28)(29)(30)(31).…”

“…Methylprednisone and dexamethasone can also be used (17). In the case of refractory hypoglycemia, plasmapheresis may rapidly reduce the IAA titer (18), and it has also been successfully treated with rituximab to deplete B lymphocytes (19).…”

Clopidogrel induced autoimmune hypoglycemia

“…There have been few case reports of IAS during clopidogrel therapy. [5][6][7][8] The proposed explanation for hypoglycemia is that the clopidogrel sulfhydryl group interacts with the insulin molecule's disulfide bond, rendering it immunogenic. Consequently, insulin autoimmune antibodies (IAAs) produced circulate in the blood.…”

Insulin Autoimmune Syndrome: A Systematic Review

“…Te most common such drugs are methimazole [16,17] and lipoic acid [18][19][20][21][22]. Others include clopidogrel [23][24][25][26], proton pump inhibitors [27] (pantoprazole [8], omeprazole), carbimazole [28], coenzyme Q10 [29], antituberculosis drugs [30], gliclazide [31], captopril [32], loxoprofen sodium [33], and albumin preparations [34], within the preceding week. Studies have shown that approximately half of IAS patients have a history of medication before the onset of the disease, and more than 90% of them used drugs containing sulfhydryl groups such as α-lipoic acid or its metabolites [35].…”