Immunological Hypoglycemia Associated with Insulin Antibodies Induced by Exogenous Insulin in 11 Chinese Patients with Diabetes

Overview

Journal J Diabetes Res

Publisher Wiley

Specialty Endocrinology

Date 2015 May 12

PMID 25961056

Citations 13

Authors

Heng Quan

Huiwen Tan

Qianrui Li

Jianwei Li

Sheyu Li

Affiliations

Soon will be listed here.

Abstract

Aims: To investigate the characteristics of immunological hypoglycemia associated with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients with diabetes.

Methods: The clinical data of patients with immunological hypoglycemia due to IAbs were retrospectively analyzed by screening patients with diabetes discharged from West China Hospital from 2007 to 2013.

Results: A total of 11 patients (eight men and three women) were identified. Insulin-C-peptide separation was found in all patients via insulin and C-peptide release test. Previous insulin use was ceased after admission and was switched to oral hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days (interquartile range [IQR], 11-40), while IAbs turned negative after a median of 17 months (IQR, 4-19), and serum immunoreactive insulin (IRI) levels dropped substantially after a median of 22 months (IQR, 9-32) in these cases.

Conclusions: In insulin-treated patients with unexpected and refractory hypoglycemia even after insulin therapy was gradually reduced or even withdrawn, IAbs induced by exogenous insulin should be considered, and insulin withdrawal might be promptly needed. The course of immunological hypoglycemia was benign and self-limited.

Citing Articles

A Case of Exogenous Insulin Autoimmune Syndrome: A Case Report.

Wang M, Jjiang G, Meng X, Wang L Cureus. 2024; 16(10):e72067.

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Exogenous insulin autoimmune syndrome: A case report and review of literature.

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The Application of the Insulin to C-Peptide Molar Ratio (ICPR) in Primary Screening for Insulin Antibodies in Type 2 Diabetes Mellitus Patients: A Further Quantitative Study on the Relationship Between ICPR and Insulin Antibodies.

Hua K, Jing B, Wu Y Diabetes Metab Syndr Obes. 2023; 16:1121-1132.

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Hsieh Y, Yeh M, Lin Y, Weng S, Hsu C, Huang C Front Endocrinol (Lausanne). 2023; 13:1099805.

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References

Raskin P, Guthrie R, LEITER L, Riis A, Jovanovic L . Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. Diabetes Care. 2000; 23(5):583-8. DOI: 10.2337/diacare.23.5.583. View

Sapin R, Le Galudec V, Gasser F, Pinget M, Grucker D . Elecsys insulin assay: free insulin determination and the absence of cross-reactivity with insulin lispro. Clin Chem. 2001; 47(3):602-5. View

Kim M, Sheeler L, Mansharamani N, Haug M, Faiman C, Gupta M . Insulin antibodies and hypoglycemia in diabetic patients. Can a quantitative analysis of antibody binding predict the risk of hypoglycemia?. Endocrine. 1997; 6(3):285-91. DOI: 10.1007/BF02820505. View

Brooks-Worrell B, Nielson D, Palmer J . Insulin autoantibodies and insulin antibodies have similar binding characteristics. Proc Assoc Am Physicians. 1999; 111(1):92-6. DOI: 10.1046/j.1525-1381.1999.09114.x. View

Harwood R . Insulin-binding antibodies and "spontaneous" hypoglycemia. N Engl J Med. 1960; 262:978-9. DOI: 10.1056/NEJM196005122621908. View

Koyama R, Nakanishi K, Kato M, Yamashita S, Kuwahara H, Katori H . Hypoglycemia and hyperglycemia due to insulin antibodies against therapeutic human insulin: treatment with double filtration plasmapheresis and prednisolone. Am J Med Sci. 2005; 329(5):259-64. DOI: 10.1097/00000441-200505000-00007. View

Fourlanos S, Dotta F, Greenbaum C, Palmer J, Rolandsson O, Colman P . Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia. 2005; 48(11):2206-12. DOI: 10.1007/s00125-005-1960-7. View

Matsuyoshi A, Shimoda S, Tsuruzoe K, Taketa K, Chirioka T, Sakamoto F . A case of slowly progressive type 1 diabetes with unstable glycemic control caused by unusual insulin antibody and successfully treated with steroid therapy. Diabetes Res Clin Pract. 2006; 72(3):238-43. DOI: 10.1016/j.diabres.2005.10.018. View

Furukawa N, Miyamura N, Nishida K, Motoshima H, Taketa K, Araki E . Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome. Diabetes Res Clin Pract. 2006; 75(3):366-7. DOI: 10.1016/j.diabres.2006.07.005. View

10.

Uchigata Y . The novel agent, alpha lipoic acid, can cause the development of insulin autoimmune syndrome. Intern Med. 2007; 46(17):1321-2. DOI: 10.2169/internalmedicine.46.0221. View

11.

Edwin Fineberg S, Kawabata T, Finco-Kent D, Fountaine R, Finch G, Krasner A . Immunological responses to exogenous insulin. Endocr Rev. 2007; 28(6):625-52. DOI: 10.1210/er.2007-0002. View

12.

Saddig C, Goretzki P, Starke A . Differentiation of insulin secretion patterns in insulinoma. World J Surg. 2008; 32(5):918-29. DOI: 10.1007/s00268-007-9450-3. View

13.

Gerstein H, Miller M, Byington R, Goff Jr D, Thomas Bigger J, Buse J . Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358(24):2545-59. PMC: 4551392. DOI: 10.1056/NEJMoa0802743. View

14.

Uchigata Y, Hirata Y, Iwamoto Y . Drug-induced insulin autoimmune syndrome. Diabetes Res Clin Pract. 2008; 83(1):e19-20. DOI: 10.1016/j.diabres.2008.10.015. View

15.

Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven P . Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2008; 360(2):129-39. DOI: 10.1056/NEJMoa0808431. View

16.

Finfer S, Chittock D, Su S, Blair D, Foster D, Dhingra V . Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009; 360(13):1283-97. DOI: 10.1056/NEJMoa0810625. View

17.

Ishizuka T, Ogawa S, Mori T, Nako K, Nakamichi T, Oka Y . Characteristics of the antibodies of two patients who developed daytime hyperglycemia and morning hypoglycemia because of insulin antibodies. Diabetes Res Clin Pract. 2009; 84(2):e21-3. DOI: 10.1016/j.diabres.2009.02.007. View

18.

Oak S, Phan T, Gilliam L, Hirsch I, Hampe C . Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin. Acta Diabetol. 2009; 47(2):131-5. PMC: 9590609. DOI: 10.1007/s00592-009-0135-2. View

19.

Zhao T, Li F, Xiong Z . Frequent reoccurrence of hypoglycemia in a type 2 diabetic patient with insulin antibodies. Mol Diagn Ther. 2010; 14(4):237-41. DOI: 10.1007/BF03256379. View

20.

Cassidy J, Luzio S, Marino M, Baughman R . Quantification of human serum insulin concentrations in clinical pharmacokinetic or bioequivalence studies: what defines the "best method"?. Clin Chem Lab Med. 2012; 50(4):663-6. DOI: 10.1515/cclm-2011-0860. View