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Diabetes Care. 2012 Jun;35(6):1213-8. doi: 10.2337/dc11-2081. Epub 2012 Mar 23.

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

Collaborators (331)

Skyler JS, Anderson M, Bourcier K, Becker D, Bingley P, Blum J, Bosi E, Buckner J, Chase H, Clare-Salzler M, Colman P, DiMeglio L, Eisenbarth GS, Fathman C, Gitelman S, Goland R, Gottlieb P, Grave G, Greenbaum C, Harrison L, Herold K, Insel R, Krischer JP, Mahon J, Marks J, Moran A, Palmer JP, Peakman M, Pugliese A, Raskin P, Roncarolo MG, Russell W, Savage P, Schatz D, Sherwin R, Siegelman M, Simell O, Thomas J, Trucco M, Wagner J, Wherrett D, Wilson DM, Winter W, Fradkin J, Leschek E, Spain L, Benoist C, Bluestone J, Brown D, Cowie C, Hering B, Jordan S, Kaufman FR, Lachin JM, Nanto-Salonen K, Nepom G, Orban T, Parkman R, Pescovitz M, Peyman J, Ridge J, Rodriguez H, Ziegler A, Skyler JS, Bourcier K, Greenbaum CJ, Krischer JP, Leschek E, Rafkin L, Savage P, Spain L, Cowie C, Foulkes M, Krause- Steinrauf H, Lachin JM, Malozowski S, Peyman J, Ridge J, Zafonte SJ, Skyler JS, Greenbaum CJ, Kenyon NS, Rafkin L, Santiago I, Sosenko JM, Krischer JP, Bundy B, Luvon Ritzie AQ, Abbondondolo M, Adams T, Alies P, Badias F, Beam C, Boonstra M, Boulware D, Cuthbertson D, Eberhard C, Ford J, Ginem J, Guillette H, Hays B, Henry M, Law P, Linton C, Liu S, Lloyd J, Muller S, O'Donnell R, Parrimon Y, Paulus K, Pilger J, Ramiro J, Roberts A, Sadler K, Terry A, Wootten M, Xu P, Young K, Bassi M, Freeman D, Granger M, Kieffer M, Nallamshetty L, Shor A, Lachin JM, Foulkes M, Harding P, Krause-Steinrauf H, McDonough S, McGee PF, Owens Hess K, Phoebus D, Quinlan S, Raiden E, Fradkin J, Leschek E, Savage P, Spain L, Blumberg E, Braun J, Laffel L, Naji A, Nerup J, Orchard T, Tsiatis A, Veatch R, Wallace D, Lernmark A, Lo B, Mitchell H, Steffes M, Zinman B, Loechelt B, Baden L, Green M, Weinberg A, Eisenbarth GS, Marcovina S, Palmer JP, Weinberg A, Winter W, Yu L, Babu S, Orban T, Gottlieb P, Greenbaum C, Krause-Steinrauf H, Lachin JM, Leschek E, Loechelt B, Parkman R, Rafkin L, Rigby A, Skyler JS, Spain L, Wagner J, Greenbaum C, Bollyky J, Sanda S, Tridgell D, McCulloch-Olson M, Vendettuoli H, Hefty D, Ramey M, Webber C, Kuhns K, Hilderman N, Dove A, Hammond M, Klein J, Batts E, Monzavi R, Halvorson M, Bock M, Fisher L, Jeandron D, Wood J, Kaufman FR, Goland R, Greenberg E, Gallagher MP, Trast J, Chan M, Rodriguez H, Pescovitz M, DiMeglio L, Christner L, Nicholson M, Mendez M, Orban T, Benoist C, Wolfsdorf J, Ricker A, Jalahej H, Conboy D, Kis J, Zhang H, Fay S, Wilson DM, Buckingham BA, Aye T, Esrey T, Soto A, Perry J, Baker B, Rigby A, Berry B, Gitelman SE, Rosenthal SM, Anderson M, Adi S, Breen K, Hamilton C, Gottlieb P, Chase H, Michels A, Kastelic W, Weiner L, Schatz D, Haller M, Clare-Salzler M, Cook R, Mancini D, Abraham A, Hicks E, Cole G, Marks JB, Pugliese A, Matheson D, Blaschke C, Arazo L, Cisneros M, Acosta B, Moran A, Nathan B, Wagner J, Boes MA, Gibson C, Finney L, Albright-Fischer T, Smith J, Becker D, Toledo F, Libman I, Riley K, Delallo K, Smith K, Gwynn D, Wohlers G, Raskin P, White P, Dickson B, Adhikari S, Siegelman M, Alford M, Torres N, Harden T, Pruneda L, Cordova E, Davis R, Fernandez S, Arthur J, Wherrett D, Eisel LA, Ahenkorah B, Razack N, Sriskandarajah M, Russell WE, Thomas JW, Moore DJ, Brown A, Black M, Pittel E, Brendle F, Bosi E, Battaglia M, Belloni C, Bianconi E, Falqui L, Grogan P, Lombardoni C, Martinenghi S, Grogan P, Bingley P, Aitken R, Castleden H, Farthing N, Matthews C, McGee J, Wheaton C, Harrison LC, Andaloro E, Breen C, Colman P, Fourlanos S, Gellert S, Healy F, Wentworth J, Simell OG, Kallio T, Mantymaki E, Nanto-Salonen K, Niininen T, Nurmi B, Romo M, Ruohonen E, Sarma M, Simell T, Suomenrinne S, Farkas K, Torma M.

Author information

1
Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, Colorado, USA.

Abstract

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.

PMID:
22446173
PMCID:
PMC3357246
DOI:
10.2337/dc11-2081
[Indexed for MEDLINE]
Free PMC Article

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