Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.

Yu L, Boulware DC, Beam CA, Hutton JC, Wenzlau JM, Greenbaum CJ, Bingley PJ, Krischer JP, Sosenko JM, Skyler JS, Eisenbarth GS, Mahon JL, Type 1 Diabetes TrialNet Study Group
Diabetes Care. 2012 35 (6): 1213-8

PMID: 22446173 · PMCID: PMC3357246 · DOI:10.2337/dc11-2081

OBJECTIVE - We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A).

RESEARCH DESIGN AND METHODS - For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives.

RESULTS - ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA(+) vs. 8 of 911 [0.8%] BAA(-), P < 0.001) and BAA number (177 of 1,683 [10.5%] single-, 221 of 384 [57.6%] double-, and 150 of 189 [79.4%] triple-BAA positivity, P < 0.001). The 4-year diabetes risk was higher in single BAA(+) relatives with ZnT8A than ZnT8A(-) relatives (31 vs. 7%, P < 0.001). In multivariable analysis, age ≤ 20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively).

CONCLUSIONS - In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.

MeSH Terms (21)

Adolescent Adult Autoantibodies Cation Transport Proteins Child Child, Preschool Cohort Studies Diabetes Mellitus, Type 1 Family Female Genotype Glucose Tolerance Test Humans Infant Male Middle Aged Predictive Value of Tests Risk Assessment Risk Factors Young Adult Zinc Transporter 8

Connections (1)

This publication is referenced by other Labnodes entities: