Diabetes & Metabolism Journal

Original Articles

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies: Suk Chon, Moon Chan Choi, Yun Jung Lee, You Cheol Hwang, In-Kyung Jeong, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-Taek Woo, Sung-Woon Kim, Jin-Woo Kim, Young Seol Kim; Diabetes Metab J. 2011;35(1):80-85. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.80

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Background

Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.

Methods

To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.

Results

In the patient's pre-treatment serum IgG, the binding of ¹²⁵I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10^-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.

Conclusion

We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

Citations

Citations to this article as recorded by

Systematic Review—Type B Insulin Resistance With Isolated Hypoglycemia and Suppressed Insulin
Natasha Brown, Marianne S Elston
The Journal of Clinical Endocrinology & Metabolism.2024; 109(4): 936. CrossRef
Type B insulin resistance syndrome: a systematic review
Luizianne Mariano Martins, Virgínia Oliveira Fernandes, Manuela Montenegro Dias de Carvalho, Daniel Duarte Gadelha, Paulo Cruz de Queiroz, Renan Magalhães Montenegro
Archives of Endocrinology and Metabolism.2020;[Epub] CrossRef
Autoimmune hypoglycemia
Marina Y. Yukina, Diana A. Davtyan, Ekaterina A. Troshina, Nurana F. Nuralieva
Obesity and metabolism.2018; 15(3): 9. CrossRef
Unique pharmacology of a novel allosteric agonist/sensitizer insulin receptor monoclonal antibody
Simon A. Hinke, Anne M. Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L. Chiu, Steve Jarantow, Eilyn R. Lacy, Yin Liang, Dana L. Johnson, Jean M. Whaley, Russell B. Lingham
Molecular Metabolism.2018; 10: 87. CrossRef
Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study
Joanna Klubo-Gwiezdzinska, Maria Lange, Elaine Cochran, Robert K. Semple, Cornelia Gewert, Rebecca J. Brown, Phillip Gorden
Diabetes Care.2018; 41(11): 2353. CrossRef
Hypoinsulinemic Hypoglycemia Followed By The Onset Of Severe Insulin Resistance With Hyperglycemia And Circulating Anti-Insulin Receptor Antibodies In A Patient Suffering Systemic Lupus Erythematosus: A Case Report And Literature Review
Guillermo Martínez de Pinillos, Mariana Tomé, María M. Viloria, Joaquín Bobillo, María V. Cózar
AACE Clinical Case Reports.2017; 3(3): e284. CrossRef
The treatment of hyperinsulinemic hypoglycaemia in adults: an update
M. V. Davi′, A. Pia, V. Guarnotta, G. Pizza, A. Colao, A. Faggiano
Journal of Endocrinological Investigation.2017; 40(1): 9. CrossRef
Immunosuppressive Therapy in Treatment of Refractory Hypoglycemia in Type B Insulin Resistance: A Case Report
Lavanya Viswanathan, Imali Sirisena
Journal of the Endocrine Society.2017; 1(12): 1435. CrossRef
反復する低血糖発作を契機に発見されたインスリン受容体異常症B型の1例(A case of type B insulin resistance presenting as recurrent hypoglycemia)
杉本龍 (Ryu Sugimoto), 髙木誠 (Makoto Takaki), 前原潤一 (Junichi Maehara), 具嶋泰弘 (Yasuhiro Gushima)
Nihon Kyukyu Igakukai Zasshi: Journal of Japanese Association for Acute Medicine.2017; 28(3): 100. CrossRef
Type B insulin resistance syndrome
Devina L. Willard, Mary Stevenson, Devin Steenkamp
Current Opinion in Endocrinology, Diabetes & Obesity.2016; 23(4): 318. CrossRef
Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans
Christelle Liminet, Julien Vouillarmet, Karim Chikh, Emmanuel Disse
Canadian Journal of Diabetes.2016; 40(5): 462. CrossRef
The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
Adel A.A. Ismail
Clinical Chemistry and Laboratory Medicine (CCLM).2016; 54(11): 1715. CrossRef
Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease
Seon Mee Kang, Heung Yong Jin, Kyung Ae Lee, Ji Hyun Park, Hong Sun Baek, Tae Sun Park
The Korean Journal of Internal Medicine.2013; 28(1): 98. CrossRef
Treatment of recurrent hypoglycemia with plasmapheresis and steroid in nondiabetic patient
Mustafa Kulaksızoglu, Mustafa Sait Gonen, Levent Kebapcilar, Fatih Sahin, Fatih Demirci, Ali Topcu
Transfusion and Apheresis Science.2013; 48(1): 11. CrossRef
A Case of Persistent Hypoglycemia: When to Think Outside the Box
Yogeswari Venugopal, Shireene Vethakkan, Sargunan Sockalingam, Raja Jasmin, Karen Choong
Clinical Diabetes.2013; 31(3): 130. CrossRef
The effect of hyperglycemia and hypoglycemia on glucose transport and expression of glucose transporters in human lymphocytes B and T: An in vitro study
Bożenna Oleszczak, Leszek Szablewski, Monika Pliszka
Diabetes Research and Clinical Practice.2012; 96(2): 170. CrossRef
The effect of glucose concentrations in the medium on expression of insulin receptors in human lymphocytes B and T: anin vitrostudy
Bożenna Oleszczak, Leszek Szablewski, Monika Pliszka
Journal of Receptors and Signal Transduction.2012; 32(5): 263. CrossRef
Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome
H. S. Kim, T.‐Y. Lee, E. Y. Kim, J. H. Choi, S. Y. Kim, Y.‐C. Hwang, J.‐H. Kang, K. J. Ahn, H. Y. Chung, I.‐K. Jeong
Diabetic Medicine.2012; 29(10): 1335. CrossRef
A Case of the Type B Insulin Resistance Syndrome with Chronic Hepatitis B
Hyun Seok Choi, Byoung Ho Choi, Seok Hoo Jeong, Shung Han Choi, Dong Su Shin, Sei hyun Kim, Young Sil Eom, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Ki Young Lee
Endocrinology and Metabolism.2011; 26(4): 360. CrossRef

The Changes in Early Phase Insulin Secretion in Newly Diagnosed, Drug Naive Korean Prediabetes Subjects: Sang Youl Rhee, Joo Young Kim, Suk Chon, You Cheol Hwang, In Kyung Jeong, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-taek Woo, Sung Woon Kim, Jin-Woo Kim, Young Seol Kim; Korean Diabetes J. 2010;34(3):157-165. Published online June 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.3.157

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29 Download
15 Crossref

Abstract PDF PubReader

Background

There have been no systematic observations regarding changes in early phase insulin secretion among Korean prediabetes and early stage type 2 diabetes mellitus (T2DM) patients.

Methods

We conducted 75-g oral glucose tolerance tests (OGTT) in 873 subjects with suspected abnormal glucose tolerance. All subjects were diagnosed as having normal glucose tolerance (NGT), prediabetes (preDM), or T2DM according to the OGTT results and the insulin secretory and insulin resistance indices of each subject were calculated. Additionally, we analyzed the changes in early phase insulin secretion according to changes in fasting (Glc₀), post-prandial (Glc₁₂₀) glucose and HbA1c (A1c) levels.

Results

As compared to subjects with NGT, the insulin secretory indices of the preDM and T2DM subjects progressively declined, and the insulin resistance indices were progressively aggravated. Early phase insulin secretion decreased rapidly according to the increments of Glc₀, Glc₁₂₀ and A1c, and these changes were most prominent in the NGT stage. Compared to the control group, the early phase insulin secretion levels of the preDM or T2DM subjects were less than 50% when Glc₀ was over 100 mg/dL, Glc₁₂₀ was over 145 mg/dL, and A1c was over 5.8%.

Conclusion

This study suggests that progressive beta cell dysfunction in Koreans may be initiated and rapidly aggravated during the period generally designated as 'normal.'

Citations

Citations to this article as recorded by

Hospital-Based Korean Diabetes Prevention Study: A Prospective, Multi-Center, Randomized, Open-Label Controlled Study
Sang Youl Rhee, Suk Chon, Kyu Jeung Ahn, Jeong-Taek Woo
Diabetes & Metabolism Journal.2019; 43(1): 49. CrossRef
Differential role of insulin resistance and β-cell function in the development of prediabetes and diabetes in middle-aged and elderly Chinese population
Xueli Cai, Lili Xia, Yuesong Pan, Dian He, Huiping Zhu, Tiemin Wei, Yan He
Diabetology & Metabolic Syndrome.2019;[Epub] CrossRef
Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism
Mi Kyung Kwak, Jee Yang Lee, Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh
Journal of Clinical Medicine.2019; 8(12): 2194. CrossRef
Insulin resistance increases the risk of incident type 2 diabetes mellitus in patients with non‐alcoholic fatty liver disease
Yuya Seko, Yoshio Sumida, Saiyu Tanaka, Kojiroh Mori, Hiroyoshi Taketani, Hiroshi Ishiba, Tasuku Hara, Akira Okajima, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Kazuyuki Kanemasa, Kohichiroh Yasui, Shunsuke Imai, Keiji Shim
Hepatology Research.2018;[Epub] CrossRef
Longitudinal Changes in Insulin Resistance, Beta-Cell Function and Glucose Regulation Status in Prediabetes
Chul-Hee Kim, Hong-Kyu Kim, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Joong-Yeol Park
The American Journal of the Medical Sciences.2018; 355(1): 54. CrossRef
Prenatal Dexamethasone Exposure Programs the Development of the Pancreas and the Secretion of Insulin in Rats
Yu-Chieh Chen, Ying-Hua Huang, Jiunn-Ming Sheen, You-Lin Tain, Hong-Ren Yu, Chih-Cheng Chen, Miao-Meng Tiao, Ho-Chang Kuo, Li-Tung Huang
Pediatrics & Neonatology.2017; 58(2): 135. CrossRef
Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
Jong-Dai Kim, Won-Young Lee
Endocrinology and Metabolism.2016; 31(3): 354. CrossRef
The effect of glargine versus glimepiride on pancreatic β-cell function in patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label, randomized, controlled study
Jun Sung Moon, Kyoung Soo Ha, Ji Sung Yoon, Hyoung Woo Lee, Hyun Chul Lee, Kyu Chang Won
Acta Diabetologica.2014; 51(2): 277. CrossRef
Association of Obstructive Sleep Apnea and Glucose Metabolism in Subjects With or Without Obesity
Nan Hee Kim, Nam H. Cho, Chang-Ho Yun, Seung Ku Lee, Dae Wui Yoon, Hyun Joo Cho, Jae Hee Ahn, Ji A. Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Chol Shin
Diabetes Care.2013; 36(12): 3909. CrossRef
Relative contributions of insulin resistance and β‐cell dysfunction to the development of Type 2 diabetes in Koreans
C.‐H. Kim, H.‐K. Kim, E. H. Kim, S. J. Bae, J.‐Y. Park
Diabetic Medicine.2013; 30(9): 1075. CrossRef
Associations among Body Mass Index, Insulin Resistance, and Pancreatic β-Cell Function in Korean Patients with New-Onset Type 2 Diabetes
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
The Korean Journal of Internal Medicine.2012; 27(1): 66. CrossRef
High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)
Y. Heianza, Y. Arase, K. Fujihara, H. Tsuji, K. Saito, S. D. Hsieh, S. Kodama, H. Shimano, N. Yamada, S. Hara, H. Sone
Diabetic Medicine.2012; 29(10): 1285. CrossRef
The Prediabetic Period: Review of Clinical Aspects
Sang Youl Rhee, Jeong-Taek Woo
Diabetes & Metabolism Journal.2011; 35(2): 107. CrossRef
Predictive characteristics of patients achieving glycaemic control with insulin after sulfonylurea failure
Y.-H. Lee, B.-W. Lee, S. W. Chun, B. S. Cha, H. C. Lee
International Journal of Clinical Practice.2011; 65(10): 1076. CrossRef
Early Insulin Secretory Dysfunction in Korean Prediabetic Subjects: Should We Change the Criteria for "Prediabetes?"
Chul-Hee Kim
Korean Diabetes Journal.2010; 34(3): 154. CrossRef

Effects of Islet Transplantation on Endogenous beta-cell Regeneration after Partial Pancreatectomy in Rodents.: Hye Seung Jung, You Ran Ahn, Seung Hoon Oh, Jung Hwa Jung, Tae Hyun Kim, You Cheol Hwang, Mira Kang, Yongsuk Bae, Young seok Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2007;31(2):113-122. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.113

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Abstract PDF: BACKGROUND
Islet transplantation is one of regimens supplying the deficient insulin in diabetes patients, but the effects of islet grafts on the changes of endogenous beta-cells are not clear. In the present study, we examined the changes of endogenous beta-cell mass after islet transplantation in partially pancreatectomized mice. METHODS: Balb/c mice were 70% pancreatectomized, transplanted with syngeneic islets (group IV), and were compared with pancreatectomized mice treated with insulin (group III) or no insulin (group II). Blood glucose levels and body weight were monitored. Remnant pancreas was obtained at 6 or 10 days after pancreatectomy, and immunohistochemical staining was done for the evaluation of beta-cell mass changes. RESULTS: Hyperglycemia and weight loss were induced after pancreatectomy. After islet transplantation or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. Plasma insulin levels were higher and beta-cell mass was larger in group IV than in group II (P < 0.05). Especially, the difference of beta-cell mass between them was more evident at 7 days as compared to at 3 day after transplantation. When compared to group III, group IV showed larger individual beta-cell area after 7 days and larger beta-cell mass after 3 days of islet transplantation (P < 0.05). CONCLUSION: These observations indicate that islet transplantation plays a role in enhancing remnant beta-cell regeneration after partial pancreatectomy in rodents.

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