Clinical features of cases of seroconversion of anti-glutamic acid decarboxylase antibody during the clinical course of type 2 diabetes: a nationwide survey in Japan
- 197 Downloads
The pathogenesis of type 1 diabetes is different from that of type 2 diabetes, and anti-glutamic acid decarboxylase antibody (GADA) helps to diagnose autoimmune type 1 diabetes. Some studies reported that GADA seroconversion occurs during the clinical course of type 2 diabetes, leading to development of “type 1 on type 2 diabetes”. To clarify the clinical characteristics and triggers of GADA seroconversion, we performed a nationwide questionnaire survey for clinical cases identified by literature search, and obtained information on 38 cases (24 with insulin therapy and 14 without it). The diabetes duration up to determination of GADA seroconversion was significantly longer in the group with insulin therapy than that without it. This finding was particularly noted in insulin-treated non-obese patients with lower serum C-peptide levels. In these patients, insulin therapy could have masked sudden increases in plasma glucose and HbA1c levels, possibly leading to delayed determination of GADA seroconversion. In non-obese patients without insulin therapy, an abrupt rise in the plasma glucose and HbA1c levels was observed at immediately before the determination, a finding which may help to predict GADA seroconversion. From the results of the present survey, we could not determine apparent triggers of GADA seroconversion. Thus, physicians may need to consider the possibility of concurrent type 1 diabetes during the therapeutic course of type 2 diabetes; GADA measurement should be considered when non-obese type 2 diabetic patients not receiving insulin therapy experience unexpected abrupt hyperglycemia and when those receiving insulin therapy show low serum C-peptide levels.
KeywordsAnti-glutamic acid decarboxylase antibody Seroconversion Type 1 on type 2 diabetes
In addition to the authors, the following doctors (affiliations at the time) assisted in conducting the present nationwide survey, for which we are extremely grateful: Drs. T. Asano (Saitama Medical Center, Jichi Medical University), F. Egashira (Nihon University Hospital), H. Fujita (Tama-Hokubu Medical Center), M. Go (Seikeikai Hospital), S. Hasegawa (National Hospital Organization Kyoto Medical Center), M. Higa (Saiseikai Yokohamashi Tobu Hospital), Y. Itoh (Meinan Hospital), Y. Itoh (Shimane Prefectural Central Hospital), H. Kanno, J. Miura (Tokyo Women’s Medical University Hospital), T. Kawai (Keio University Hospital), J. Morimoto (Japan Community Health care Organization, Saitama Medical Center), R. Nagase (Okayama Rosai Hospital), K. Nagayama (Hamamatsu Medical Center), Y. Nakajima (Nippon Medical School Hospital), Y. Nakamura (Kawanishi City Hospital), M. Ogimoto (Chihaya Hospital), M. Ogura (Kyoto University Hospital), T. Okumura (Tokyo Medical University Hospital), F. Sawano (Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital), Y. Sekiguchi (Ome Municipal General Hospital), Y. Shintani (Tokushima Red Cross Hospital), K. Takeda (Yamaguchi University Hospital) and T. Uto (Kagoshima City Hospital).
Compliance with ethical standards
Conflict of interest
Author HI received scholarship grants from Sumitomo Dainippon Pharma Co., Ltd, Ono Pharmaceutical Co., LTD., Otsuka Pharmaceutical Co., Ltd., Boehringer Ingelhaim Japan, Inc., Daiichi Sankyo Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Johnson & Johnson K.K. Author HI received honoraria for lectures from Novo Nordisk Pharma Ltd., Sumitomo Dainippon Pharma Co., Ltd, Kowa Co., Ltd., Astellas Pharma Inc., Eli Lilly Japan K.K. Author AI received a clinical research grant from Mochida Pharmaceutical Co., Ltd. Author AI received scholarship grants from Daiichi Sankyo Company Ltd., Astellas Pharma Inc., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., AstraZeneca K.K. Author YK received scholarship grants from Sumitomo Dainippon Pharma Co., Ltd, Ono Pharmaceutical Co., LTD., Otsuka Pharmaceutical Co., Ltd., Boehringer Ingelhaim Japan, Inc., Daiichi Sankyo Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Johnson & Johnson K.K. Author TH received a scholarship grant from Astellas Pharma Inc. Authors YO, AS, TA, TF, HK, EK, JM, HO, KT, ST, YU, HY, KY, and TK declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.
- 6.Kawasaki E, Maruyama T, Imagawa A, et al. Proposal of diagnostic criteria for acute-onset type 1 diabetes mellitus (2012) Report of the Committee of the Japan Diabetes Society on the Research of Fulminant and Acute-onset. J Japan Diab Soc. 2013;56:584–9.Google Scholar
- 7.Tanaka S, Ohmori M, Awata T, et al. Diagnostic criteria for slowly progressive insulin-dependent (Type 1) diabetes mellitus (SPIDDM) (2012) Report by the Committee on Slowly Progressive Insulin-dependent (Type 1) Diabetes Mellitus of the Japan Diabetes Society. J Japan Diab Soc. 2013;56:590–7.Google Scholar
- 11.Tanaka S, Awata T, Shimada A, et al. Clinical characteristics of slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM): 1st Subcommittee Report on SPIDDM, Committee on Type 1 Diabetes, Japan Diabetes Society. J Japan Diab Soc. 2011;54:65–75.Google Scholar
- 14.Kasuga A, Maruyama T, Morimoto J, et al. Cutoff GAD 65 antibody titer to predict insulin-requirement in diabetic patients with non-insulin-dependent diabetes mellitus. J Japan Diab Soc. 2000;43:935–40.Google Scholar