The diagnostic value of zinc transporter 8 autoantibody (ZnT8A) for type 1 diabetes in Chinese

Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.55). 10/2010; 26(7):579-84. DOI: 10.1002/dmrr.1128
Source: PubMed


Zinc transporter-8 (ZnT8) was recently identified as a novel autoantigen in human type 1 diabetes (T1D). Autoantibody to ZnT8 (ZnT8A) was detected in up to 80% of patients with new-onset T1D and 26% of patients with T1D otherwise classified as negative on the basis of existing markers. As no data of ZnT8A in Chinese have been reported, we aim to evaluate the utility of ZnT8A for diagnosis of autoimmune T1D in Chinese relative to other autoantibody markers.
Radioligand binding assays were performed on 539 T1D sera using human ZnT8 carboxyterminal 325Arg construct or a dimer incorporating 325Arg and 325Trp alongside antibodies to glutamic acid decarboxylase (GADA) or insulinoma-associated protein 2 (IA-2A). The antigenic specificity was analysed in the context of clinical characteristics of the patients.
ZnT8A were present in 24.1% (130 of 539) of patients with T1D versus 1.8% (10 of 555; P < 0.001) in type 2 diabetes. At diagnosis, ZnT8A and IA-2A were less prevalent in Chinese subjects with T1D than in Caucasian populations (both P < 0.001) but similar to Japanese. The diagnostic sensitivity of combined GADA, IA-2A and ZnT8A measurements reached 65.5% with ZnT8A detected in 13.5% (29 of 215) of GADA and/or IA-2A-negative subjects. ZnT8A prevalence was lower in older and fatter patients. ZnT8A+ alone patients were distinguished from Ab- ones (P < 0.05-0.001) on the basis of higher insulin requirement and lower systolic blood pressure level.
ZnT8A is an independent marker for T1D in Chinese and combined with GADA and IA-2A enhances diagnostic sensitivity. ZnT8A may be associated with different clinical phenotypes than GADA or IA-2A.

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Available from: Lin Yang, Jan 22, 2014
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    • "Serum was analyzed for the presence of GAD-Ab by highly sensitive and specific quantitative radioligand binding assay methods as reported previously [12]. Intra-assay and inter-assay coefficients of variation were 8.9% and 11.2% (n=5) respectively. "
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    ABSTRACT: Background Diabetic patients with positive glutamic acid decarboxylase antibody (GAD-Ab) could be classified as autoimmune diabetes, which is discriminated into acute-onset classical type 1 diabetes (T1DM) and latent autoimmune diabetes in adults (LADA). However, whether the decay rate of beta cell function is relevant with the mode of onset (acute or latent-onset) is unclear. We aimed to investigate whether initial C peptide levels could help differentiate variation of C peptide decay rate. Methods Five hundred and twenty-seven newly diagnosed GAD-Ab positive diabetic patients were followed up to assess the natural course of beta cell function. Beta cell function failure was defined as fasting C peptide and postprandial C peptide levels less than 100 pmol/L and 150 pmol/L respectively. Results All these diabetic patients were discriminated according to initial fasting C peptide of 300 pmol/L, that is B+ (larger than 300 pmol/L) and B- (less than 300 pmol/L) group. The proportion of developing beta cell function failure was 13.1% in B+ group and 90.5% in B- group, which suggested that fasting C peptide levels made a good distinction of the heterogeneity in autoimmune diabetes. Receiver operator characteristic (ROC) analysis suggested that the fasting C peptide level of 300 pmol/L was optimal for determining beta cell function failure with sensitivity of 90.5% and specificity of 86.9%. Conclusions Initial level of fasting C peptide is a good indicator for predicting beta cell function failure in GAD-Ab positive diabetic patients.
    Full-text · Article · Mar 2013 · BMC Endocrine Disorders
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    • "It has been recently defined as a major target of humoral autoimmunity in human T1D based on a bioinformatics analysis (Dang et al., 2011; Wenzlau et al., 2009). Autoantibodies to ZnT8 (ZnT8A) have been therefore detected in high prevalence in newly diagnosed type 1 diabetic patients (Yang et al., 2010) and obviously overlap with GADA, IA2A, and IAA (Wenzlau et al., 2007). Of note, ZnT8 autoimmunity could be an independent marker of T1D, given that ZnT8As can be present in antibody-negative individuals and in type 2 diabetes, and in patients with other autoimmune disorders (Wenzlau et al., 2008). "

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    ABSTRACT: Fibroblast growth factor (FGF) 21 is an endocrine factor with multiple beneficial effects on glucose and lipid metabolism in animals. This study aimed to investigate the association of serum FGF21 levels with type 1 diabetes, latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Serum FGF21 levels were determined by ELISA in patients with type 1 diabetes (n = 76), LADA (n = 68), type 2 diabetes (n = 77), and their age- and sex-matched controls. The association of serum FGF21 with markers of autoimmunity was studied. In type 1 diabetic patients, serum FGF21 levels were significantly lower than controls [108.3 (61.5-180.1) vs. 196.0 (103.7-330.9) pg/ml, P < 0.001]. In LADA patients, serum FGF21 levels were significantly lower than controls after adjustment for body mass index [210.9 (121.4-441.6) vs. 268.3 (159.5-443.6) pg/ml, P = 0.003]. By contrast, serum FGF21 levels in type 2 diabetic patients were significantly higher than controls [381.2 (244.7-531.3) vs. 301.4 (173.9-444.2) pg/ml, P = 0.006]. FGF21 levels increased progressively from type 1 diabetes, LADA, to type 2 diabetes (P < 0.001 for global trend). Furthermore, FGF21 levels correlated inversely with titers of glutamic acid decarboxylase and insulinoma-associated protein 2 autoantibodies in type 1 diabetic and LADA patients. Serum FGF21 level is increased in type 2 diabetes but decreased in type 1 diabetes and LADA. In autoimmune diabetes, the reduction in circulating FGF21 is closely associated with markers of pancreatic β-cell autoimmunity.
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