Abstract
We encountered a 68-year-old woman with type 2 diabetes who had frequent insulin-induced hypoglycemia in the morning. She had renal failure, and was on hemodialysis. The hypoglycemia in the morning was severe, induced by the small dosage of insulin, whilst she showed severe postprandial hyperglycemia. A blood test revealed high serum insulin and C-peptide levels, and a high binding rate of insulin antibody. Switching human insulin to an insulin analogue, glulisine, failed to avoid hypoglycemia. Scatchard plot analysis indicated that the high affinity site of the patient’s insulin antibody had a low affinity constant (K1) and a high binding capacity (R1) against all tested insulin, almost equivalent values reported in insulin autoimmune syndrome cases. Treatment with the glucagon-like peptide-1 analogue liraglutide ameliorated the postprandial hyperglycemia without hypoglycemia, resulting in improved glycemic stability. Furthermore, the continued use of liraglutide reduced both serum insulin level and binding rate of insulin antibody. This is the first case of using liraglutide in an insulin-antibody positive patient with renal failure on hemodialysis. Liraglutide could be an effective and safe remedy for patients with insulin antibody-related glucose instability, regardless of their renal function.
This is a preview of subscription content, log in via an institution to check access.
References
Hirata Y, Uchigata Y. Insulin autoimmune syndrome in Japan. Diabetes Res Clin Pract. 1994;24:S153–7.
Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P. Autoimmune forms of hypoglycemia. Medicine (Baltimore). 2009;88:141–53.
Takeuchi Y, Miyamoto T, Kakizawa T, Shigematsu S, Hashizume K. Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. Intern Med. 2007;46:237–9.
Wredling R, Lins PE, Adamson U. Prevalence of anti-insulin antibodies and its relation to severe hypoglycaemia in insulin-treated diabetic patients. Scand J Clin Lab Invest. 1990;50:551–7.
Ishizuka T, Ogawa S, Mori T, Nako K, Nakamichi T, Oka Y, Ito S. Characteristics of the antibodies of two patients who developed daytime hyperglycemia and morning hypoglycemia because of insulin antibodies. Diabetes Res Clin Pract. 2009;84:e21–3.
Itoh A, Saisho Y, Mitsuishi M, Oikawa Y, Kawai T, Tanaka M, Shimada A, Itoh H. Insulin glulisine may ameliorate nocturnal hypoglycemia related to insulin antibody—a case report. Diabetes Res Clin Pract. 2011;94:e53–4.
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;329:259–64.
Eguchi Y. Scatchard analysis of insulin autoantibodies in the insulin autoimmune syndrome. J Tokyo Wom Med Coll. 1989;59:1296–305.
Redmon JB, Nuttall FQ. Autoimmune hypoglycemia. Endocrinol Metab Clin North Am. 1999;8:603–18.
Matsuyoshi A, Shimoda S, Tsuruzoe K, Taketa K, Chirioka T, Sakamoto F, Sakakida M, Miyamura N, Araki E. 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;72:238–43.
Zhao TY, Li F, Xiong ZY. Frequent reoccurrence of hypoglycemia in a type 2 diabetic patient with insulin antibodies. Mol Diagn Ther. 2010;14:237–41.
Uchigata Y, Hirata Y. Insulin autoimmune syndrome (IAS, Hirata disease). Ann Med Interne (Paris). 1999;150:245–53.
Arem R. Hypoglycemia associated with renal failure. Endocrinol Metab Clin North Am. 1989;18:103–21.
Asai M, Yoshida M, Miura Y. Immunologic tolerance to intravenously injected insulin. N Engl J Med. 2006;354:307–9.
Neumiller JJ, Sonnett TE, Wood LD, Setter SM, Campbell RK. Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes. Diabetes Metab Syndr Obes. 2010;3:215–26.
DeFronzo RA, Okerson T, Viswanathan P, Guan X, Holcombe JH, MacConell L. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008;24:2943–52.
Jacobsen LV, Hindsberger C, Robson R, Zdravkovic M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br J Clin Pharmacol. 2009;68:898–905.
Yoshida M, Asai M, Miyata M, Ogawa K, Maeda H, Oiso Y. Combination therapy with liraglutide and sulfonylurea for a type 2 diabetic patient with high titer of anti-insulin antibodies produced by insulin therapy. Diabetes Res Clin Pract. 2012;96:e55–6.
Hogan AE, Tobin AM, Ahern T, Corrigan MA, Gaoatswe G, Jackson R, O’Reilly V, Lynch L, Doherty DG, Moynagh PN, Kirby B, O’Connell J, O’Shea D. Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. Diabetologia. 2011;54:2745–54.
Miyake T, Tsujimura F, Ito Y. A case of monoclonal insulin autoimmune syndrome with a suspected 20-year history: effect of one-year administration of prednisolone on insulin autoantibodies. J Jpn Diab Soc. 2009;52:45–9.
Acknowledgments
A. A. has research grants from Takeda Pharmaceutical Co., Ltd, Nihon Medi-Physics, MSD, Dainippon Sumitomo Pharm, Kowa Pharmaceutical Co., Ltd., and Otsuka Pharmaceutical Co., Ltd and is a global consultant for Eli Lilly & Co.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Tamura, Y., Kimbara, Y., Funatsuki, S. et al. A case of insulin antibody-induced glucose instability in an elderly woman with type 2 diabetes on hemodialysis, successfully ameliorated with liraglutide. Diabetol Int 4, 71–75 (2013). https://doi.org/10.1007/s13340-012-0100-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13340-012-0100-0