Tags

Type your tag names separated by a space and hit enter

Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up.
Diabetes Metab Res Rev. 2016 09; 32(6):615-22.DM

Abstract

BACKGROUND

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics.

METHODS

This 3-year follow-up study enrolled 107 LADA and 40 type 2 diabetes mellitus (T2DM) patients from October 2005 to December 2013. GADA titer, epitopes, and clinical characteristics (including fasting C-peptide and HbA1c) in LADA patients were assayed annually. The human leukocyte antigen DQ (HLA-DQ) genotypes were also analysed. The relationship between the persistence of GADA and the clinical characteristics was investigated in LADA patients.

RESULTS

After 3-year follow-up, 36.5% (39/107) LADA patients remained GADA positive (persistently positive group), 19.6% (21/107) patients fluctuated positively and negatively (fluctuating group), and 43.9% (47/107) patients became GADA negative, among which 61.7% (29/47) seroconversions occurred within 6 months of follow-up (transiently positive group). The GADA persistently positive group possessed higher titer of GADA than transiently positive group and fluctuant group (all p = 0.000), higher reactivities to middle and C-terminal regions of GAD65 than those in transiently positive group (p = 0.001 and p = 0.000, respectively), and lower baseline fasting C-peptide level than T2DM patients and transiently positive group [415(31-1862) vs 620(220-1658) pmol/L, p = 0.014; and 415(31-1862) vs 705(64-1541) pmol/L, p = 0.017, respectively]. The GADA transiently positive group retained a higher HbA1c level when compared with T2DM patients (p = 0.023). In addition, the three LADA groups shared similar frequencies of HLA-DQ susceptible haplotypes that were higher as compared with T2DM. The GADA persistently positive group had a higher annual declining rate in fasting C-peptide than T2DM patients [-14%(-174-33%) vs -1%(-27-28%), p = 0.007].

CONCLUSION

The LADA patients with GADA transient positivity account for a large proportion, whose clinical characteristics and HLA-DQ haplotypes are different from those of T2DM. The patients with high titer GADA and reactivities to GADA65 middle and C-terminal regions showed a persistent GADA positivity, in which a worse baseline and accelerated decline of β-cell function need early intervention in the practice. Copyright © 2016 John Wiley & Sons, Ltd.

Authors+Show Affiliations

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26787598

Citation

Huang, Gan, et al. "Persistence of Glutamic Acid Decarboxylase Antibody (GADA) Is Associated With Clinical Characteristics of Latent Autoimmune Diabetes in Adults: a Prospective Study With 3-year Follow-up." Diabetes/metabolism Research and Reviews, vol. 32, no. 6, 2016, pp. 615-22.
Huang G, Yin M, Xiang Y, et al. Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up. Diabetes Metab Res Rev. 2016;32(6):615-22.
Huang, G., Yin, M., Xiang, Y., Li, X., Shen, W., Luo, S., Lin, J., Xie, Z., Zheng, P., & Zhou, Z. (2016). Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up. Diabetes/metabolism Research and Reviews, 32(6), 615-22. https://doi.org/10.1002/dmrr.2779
Huang G, et al. Persistence of Glutamic Acid Decarboxylase Antibody (GADA) Is Associated With Clinical Characteristics of Latent Autoimmune Diabetes in Adults: a Prospective Study With 3-year Follow-up. Diabetes Metab Res Rev. 2016;32(6):615-22. PubMed PMID: 26787598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up. AU - Huang,Gan, AU - Yin,Min, AU - Xiang,Yufei, AU - Li,Xia, AU - Shen,Wei, AU - Luo,Shuoming, AU - Lin,Jian, AU - Xie,Zhiguo, AU - Zheng,Peilin, AU - Zhou,Zhiguang, Y1 - 2016/03/03/ PY - 2015/07/03/received PY - 2015/11/26/revised PY - 2016/01/12/accepted PY - 2016/1/21/entrez PY - 2016/1/21/pubmed PY - 2017/10/7/medline KW - glutamic acid decarboxylase antibody KW - latent autoimmune diabetes in adults KW - type 2 diabetes mellitus KW - β-cell function SP - 615 EP - 22 JF - Diabetes/metabolism research and reviews JO - Diabetes Metab Res Rev VL - 32 IS - 6 N2 - BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics. METHODS: This 3-year follow-up study enrolled 107 LADA and 40 type 2 diabetes mellitus (T2DM) patients from October 2005 to December 2013. GADA titer, epitopes, and clinical characteristics (including fasting C-peptide and HbA1c) in LADA patients were assayed annually. The human leukocyte antigen DQ (HLA-DQ) genotypes were also analysed. The relationship between the persistence of GADA and the clinical characteristics was investigated in LADA patients. RESULTS: After 3-year follow-up, 36.5% (39/107) LADA patients remained GADA positive (persistently positive group), 19.6% (21/107) patients fluctuated positively and negatively (fluctuating group), and 43.9% (47/107) patients became GADA negative, among which 61.7% (29/47) seroconversions occurred within 6 months of follow-up (transiently positive group). The GADA persistently positive group possessed higher titer of GADA than transiently positive group and fluctuant group (all p = 0.000), higher reactivities to middle and C-terminal regions of GAD65 than those in transiently positive group (p = 0.001 and p = 0.000, respectively), and lower baseline fasting C-peptide level than T2DM patients and transiently positive group [415(31-1862) vs 620(220-1658) pmol/L, p = 0.014; and 415(31-1862) vs 705(64-1541) pmol/L, p = 0.017, respectively]. The GADA transiently positive group retained a higher HbA1c level when compared with T2DM patients (p = 0.023). In addition, the three LADA groups shared similar frequencies of HLA-DQ susceptible haplotypes that were higher as compared with T2DM. The GADA persistently positive group had a higher annual declining rate in fasting C-peptide than T2DM patients [-14%(-174-33%) vs -1%(-27-28%), p = 0.007]. CONCLUSION: The LADA patients with GADA transient positivity account for a large proportion, whose clinical characteristics and HLA-DQ haplotypes are different from those of T2DM. The patients with high titer GADA and reactivities to GADA65 middle and C-terminal regions showed a persistent GADA positivity, in which a worse baseline and accelerated decline of β-cell function need early intervention in the practice. Copyright © 2016 John Wiley & Sons, Ltd. SN - 1520-7560 UR - https://www.unboundmedicine.com/medline/citation/26787598/Persistence_of_glutamic_acid_decarboxylase_antibody__GADA__is_associated_with_clinical_characteristics_of_latent_autoimmune_diabetes_in_adults:_a_prospective_study_with_3_year_follow_up_ L2 - https://doi.org/10.1002/dmrr.2779 DB - PRIME DP - Unbound Medicine ER -