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Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5.

Xiang Y, Huang G, Shan Z, Pan L, Luo S, Yang L, Shi L, Li Q, Leslie RD, Zhou Z - Acta Diabetol (2015)

Bottom Line: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus.Clinical data were determined locally.IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively.

View Article: PubMed Central - PubMed

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

ABSTRACT

Aims: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects.

Methods: LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally.

Results: Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05).

Conclusions: As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies.

No MeSH data available.


Related in: MedlinePlus

Histogram of different assay strategy for GADA, ZnT8A, IA-2A, and IAA in adult-onset autoimmune diabetes. x axis stands for different diabetes-associated islet autoantibodies combination strategies. y axis stands for the percentage of patients with different assay strategies in a total of 206 adult autoimmune diabetes
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Fig2: Histogram of different assay strategy for GADA, ZnT8A, IA-2A, and IAA in adult-onset autoimmune diabetes. x axis stands for different diabetes-associated islet autoantibodies combination strategies. y axis stands for the percentage of patients with different assay strategies in a total of 206 adult autoimmune diabetes

Mentions: Of 2388 patients studied, 206 cases (8.6 %) had islet autoantibodies, of which the majority (177/206; 85.9 %) had a single positive autoantibody, more than had two autoantibodies (17/206; 8.3 %), in turn, more than had three autoantibodies (11/206; 5.3 %). Only one case had all four islet autoantibodies. Overlap of positive autoantibodies is shown in Fig. 1. Of note the majority of autoantibody positive cases had GADA (138/206, 67 %) (Fig. 2). Of 206 patients with autoantibodies, a combination assay with GADA plus one other autoantibody could identify 80.1 % (with IAA), 79.6 % (with ZnT8A), and 77.7 % (with IA2A), respectively (Fig. 2).The hierarchy of likelihood for detecting autoimmune diabetes by autoantibody testing in this cohort was GADA > IAA > ZnT8A > IA2A. When assaying this cohort with three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify about 92.2 % (190/206) of autoimmune diabetes patients of the total of 8.6 % with autoantibodies (Fig. 2). We have investigated the positivity of IAA, ZnT8A, and IA2A among high and low GADA titer subgroups, and there was no statistical differences for the presence of these autoantibodies in the different GADA titer groups (data not shown).Fig. 1


Glutamic acid decarboxylase autoantibodies are dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes: LADA China study 5.

Xiang Y, Huang G, Shan Z, Pan L, Luo S, Yang L, Shi L, Li Q, Leslie RD, Zhou Z - Acta Diabetol (2015)

Histogram of different assay strategy for GADA, ZnT8A, IA-2A, and IAA in adult-onset autoimmune diabetes. x axis stands for different diabetes-associated islet autoantibodies combination strategies. y axis stands for the percentage of patients with different assay strategies in a total of 206 adult autoimmune diabetes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4628082&req=5

Fig2: Histogram of different assay strategy for GADA, ZnT8A, IA-2A, and IAA in adult-onset autoimmune diabetes. x axis stands for different diabetes-associated islet autoantibodies combination strategies. y axis stands for the percentage of patients with different assay strategies in a total of 206 adult autoimmune diabetes
Mentions: Of 2388 patients studied, 206 cases (8.6 %) had islet autoantibodies, of which the majority (177/206; 85.9 %) had a single positive autoantibody, more than had two autoantibodies (17/206; 8.3 %), in turn, more than had three autoantibodies (11/206; 5.3 %). Only one case had all four islet autoantibodies. Overlap of positive autoantibodies is shown in Fig. 1. Of note the majority of autoantibody positive cases had GADA (138/206, 67 %) (Fig. 2). Of 206 patients with autoantibodies, a combination assay with GADA plus one other autoantibody could identify 80.1 % (with IAA), 79.6 % (with ZnT8A), and 77.7 % (with IA2A), respectively (Fig. 2).The hierarchy of likelihood for detecting autoimmune diabetes by autoantibody testing in this cohort was GADA > IAA > ZnT8A > IA2A. When assaying this cohort with three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify about 92.2 % (190/206) of autoimmune diabetes patients of the total of 8.6 % with autoantibodies (Fig. 2). We have investigated the positivity of IAA, ZnT8A, and IA2A among high and low GADA titer subgroups, and there was no statistical differences for the presence of these autoantibodies in the different GADA titer groups (data not shown).Fig. 1

Bottom Line: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus.Clinical data were determined locally.IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively.

View Article: PubMed Central - PubMed

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

ABSTRACT

Aims: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects.

Methods: LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally.

Results: Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05).

Conclusions: As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies.

No MeSH data available.


Related in: MedlinePlus