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Diabetes Care. 2013 Sep;36(9):2615-20. doi: 10.2337/dc13-0425. Epub 2013 Jul 1.

The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

Collaborators (1274)

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, Garrison 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, Winter W, 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, 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, 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, Hess KO, 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, Winter W, Yu L, Babu S, Orban T, Gottlieb P, Greenbaum C, Krause H, Leschek E, Loechelt B, Parkman R, Rafkin L, Spain L, Wagner J, 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, Farkas K, 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, Cisneros M, Acosta B, Moran A, Nathan B, Wagner J, Boes MA, 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, Russell WE, Sriskandarajah M, 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, 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, Jokipuu S, Kallio T, Mantymaki E, Nanto-Salonen K, Niininen T, Nurmi B, Romo M, Ruohonen E, Sarma M, Simell T, Suomenrinne S, Torma M, Skyler JS, Brown D, Chase HP, Collier E, Cowie C, Eisenbarth GS, Grave G, Fradkin J, Greenbaum C, Jackson RA, Kaufman FR, Krischer JP, Marks JB, Palmer JP, Ricker A, Schatz DA, Wilson D, Winter WE, Wolfsdorf J, Zeidler A, Dickler H, Eastman RC, Maclaren NK, Malone JI, Robertson R, Skyler JS, Krischer JP, Wolfsdorf J, Cowie C, Palmer JP, Greenbaum C, Cuthbertson D, Rafkin-Mervis LE, Chase H, Leschek E, Palmer JP, Chase H, Cowie C, Fradkin J, Eisenbarth GS, Greenbaum C, Herold K, Kaufman FR, Krischer JP, Marks JB, Rafkin-Mervis LE, Schatz DA, Skyler JS, Aneju B, Conboy D, Cook R, Dennis MA, Finney L, Harris S, Matheson D, McCulloch-Olsen M, Smith T, Valenzuela J, Vega N, Crofford OB, DeMets D, Lachin JM, Nerup J, Rossini A, Schiffrin A, Steffes M, Tsiatis A, Zinman B, Haider A, Haas J, Busch R, Marshilok K, Toleno N, Schade D, Katz P, Hornbeck D, Foster S, Roberts W, Vercher M, Foster C, Bower C, Hansen I, Burcell D, Anderson S, Shultz R, Sparks C, Wray J, Goldman L, Holt R, Counts D, Ostrowski D, Plotnick L, Fechner P, Donnelly C, Bourgeios P, Prosser P, Bowden B, Gunville F, McClave C, Heldt P, Ovalle F, Atchison J, Trull P, Bottomlee A, Betting S, Davis T, Wetzstein J, Clinkingbeard C, Davis J, Roosevelt T, Shamoon H, Duffy H, Anhalt H, Brussard L, Capotorto J, Sheehan P, Quyyumi S, Cohen N, Recker B, Castells S, Bastian W, AvRuskin TW, Verdia V, Quattrin T, Dwigun K, Cefalu W, Clark N, Tilton L, Corenblum B, Harries S, Whitty A, McInroy R, Smith S, Willi S, Key LA Jr, O'Rear D, Willi S, O'Rear D, Grubb R, Taylor K, Adams P, Reeves M, Reeves P, Marshall R, Tessmann E, Dwarakanathan A, Beebe C, Weintraub-Yohay I, O'Donnell P, Rich B, Imperial J, Silverman B, Edidin D, Goodman S, Brodsky I, Brodsky L, Klein D, Dolan L, Standiford D, Rogers D, Switzer C, Goldstein DE, Eichelberger D, Smith A, Ganong C, Zipf W, Dyas M, Sotos JF, Young C, Alford M, Riley W, Salai S, Raskin P, Marks J, Sachson R, Lebowitz C, Cook J, Stedman J, Indra D, Gutai J, Vinuya B, McGraw-Maly M, Feng W, Williams C, Krygsman C, Pierce M, Freemark M, Litton J, Ryan E, Todd K, Aboud D, Pacillas M, Hines J, Walczak A, Aparicio L, Harbaugh D, Bergeson M, Rozell M, Mahan E, Brooks H, Ginier P, Hensley P, Ellyn G, Heymann M, Johnson B, Tack J, Sondrol L, Hjelle T, Perry D, Albert J, Flory L, Gerrity N, Naab C, Heck J, Weber S, Mulhall P, Lansden B, Cummings E, Salisbury S, Armour C, Ratzan S, Trahiotis M, Nemery R, Carney H, Shorkey D, Fitz-Patrick D, Taniguchi A, Gunn S, Copeland K, McGirk S, Liljenquist J, Fielding C, Richards S, Best V, Rodriguez H, Freidenberg G, Amstutz L, Weir C, Tsalikian E, Hoffman R, Bayless M, Hare J, Hare K, Kyner J, Eaks G, Howard C, Moore W, Woodford B, Salyer T, Wannarachue N, Meridith R, Squires D, Deubler D, Bruschetta H, Nickels D, Dothard C, Courtney A, Marcus A, Beisswenger J, Kairys S, Boyle W, Christiano A, O'Dell R, Touchette A, Thrailkill K, Karounos D, Webb S, Moore L, Allweiss P, Anderson F, Mahon JL, McCallum J, Raffel L, Rotter J, Verne A, Davidson M, Keppler G, Banerjee S, Simon M, MacDonald M, Mokrohisky S, Speiser P, Fort P, Corrigan J, Pelkola S, Kitabchi A, Murphy M, Lambeth H, Burghen G, McGlendon P, Bondani J, LeNoye P, Alemzadeh R, Koppen M, Canas J, Lamerson M, Spencer M, Etzwiler R, Reynolds K, Eyler N, Allen P, Warner B, Rettig K, Levens KL, Davis M, Polychronakos C, Laforte D, Zeller W, McKernan J, Finn S, Powers A, Lipps J, Raghavan S, Broadstone V, Raake P, Weissberg K, Tamborlane W, Gatcomb P, Blonde L, Zimmerman T, Zimmerman R, Liebel C, Chalew S, Vargas A, Rao J, Ascani J, Compton T, Cerame B, Harbison M, Newfield R, New M, Wajnrajch M, Vargas I, Herold K, Schachner H, Feberes G, Maclaren N, Golub D, Rappaport R, McEvoy R, Thomas N, Pi-Sunyer X, Saltiel-Berzin R, Rappaport R, Koblish J, Blackett P, Comp C, Beck J, Hassing J, Hahn L, Lane J, Corley K, Larson L, Fiallo-Sharer R, Lee P, Cortez A, Varni N, Speer H, Crockett S, McDaniel W, Roberts V, Weinzimer S, Cohen P, Baker L, De Paul D, Rebecca E, Dolinar R, Block M, Krametbauer P, Frazer T, Veray G, Ahmann A, LaFranchi S, Jennings P, Kelleher A, Kummer M, Hansen J, Hunter M, LaMorticella K, Bergstrom, Rigdon M, Eckert K, Klaff L, Brazg R, Springs J, Wilson B, Isaacson E, Kuhn H, Willis D, Kaplowitz P, Genther K, Bourdony C Jr, Rivera A, Basu R, Rizza R, Whannel P, Jospe N, Utzman A, Sheikholisham B, Hiner C, Hardin D, Lindsay R, Swinyard M, Rallison M, Jarrett L, Sirstins J, Pierson K, Trevino S, Schwartz S, Dickens K, Clark S, Scroggin P, Greene G, Linarelli L, Camuro E, Hermosillo S, Estrada R, Bailey W, Fuqua J, Gitelman SE, Fountaine M, Colon G, Gonzalez de Pijem L, Nieves-Rivera F, Rivera A, Perez R, Jovanovic L, Vesterfelt S, Saenz C, Kletter G, Pihoker K, Kearns S, Keppen L, Johnson P, Krell E, Duck SC, Noble M, Thompson S, Wilson K, Soler N, McCall L, Allen H, Roumeliotis G, Chase L, Braden-Moll D, White N, Levandoski L, Malone J, Steinbrueck J, Ulbrecht JS, Lambert N, Mulhall P, Wilson T, Lane A, Smaldone A, Modilevsky T, Izquierdo R, Weinstock R, Mackowiak S, Brindak K, Wherrett D, Daneman D, Pearlman K, McLellan C, Rogers A, Ipp E, Mao C, Rushovich EH, Thorne I, Jelley D, Greer D, Metzger D, Austin A, Glasgow A, Turek J, Archer J, Nunlee-Bla G, Johnson K, Harris J, Driedbart S, Noto R, Romano A, Herl W, Guthrie R, Tatpati O, Brenner A, Lippert D, Reeves G, Swenson C, Murphy L, Dean H, Berard L, Werbel S, Bell-Farrow A, Mauseth R, Hanson J, Mishr S, DiCaria L, Wilson B, Wischmeier C, Moosa M, Levy R, Desemone J, Bentson L, Lando H, Hoelscher J, Biggs W, Carano R, Nostrand P, Achee L, Kelly J, Nolan P, Otsuka T, Heyrmann K, Autio N, Gohl K, Prendergast J, Delcher H, Hamilton Reed C, Mellman M, Herskowitz I, Hoffman W, Naas M, Dubois S, Chaykin L, Pershadsingh H, Shah H, Ettinger V, Reiner B, McLaughlin J, Levin P, Boniface A, Leigh H, Ginsberg G, Weiss D, Rosecan M, Doyle P, McAfee J, Goldfogel G, Henschel J, Gorson D, Ramos J, Bush M, Martin K, Birch B, Reimer S, Neil J, Saenger P, Dimartino-Nardi J, Capotorto J, Sheehan P, Quyyumi SA, Cohen N, Stein R, Klonoff D, de Souza J, McCarthy D, Salisbury J, Edstrom C, William MF, Brown M, Vigersky R, Smith C, Krishna A, Benson R, Murphy F, Pruchno C, Davenport M, Clarke W, McDuffie M, Melinkovich G, Bell V, Ravanam A, Will W, Leonard D, Dahms W, Scott K, Bowyer F, Leichter S, Kaplan R, Lewis S, Miller R, Cristi C, Upmanyu M, Goldberg N, Savino R, Wentworth S, Langdon D, Weideman C, Urban M, Transue D, Whitehouse F, Cara J, Shaw S, Price W, Iverson R, Slag M, Hutt J, McLean N, Moore R, Christenson R, Valika K, Nayak N, Bloch C, Strom L, Bailey TS, Varma C, Calder D, Bilger M, Larson K, Papenhausen M, Shlesinger Y, Kenien A, Wright E, Lorber D, Jabbar MA, Berkett J, Bautista JL, Robinson R, Kadambi A, Sullivan W, Meyer E, Norwood PC, Biederman E, Nassberg S, Goscin L, Mata M, Bautista JL, Norwood PC, Cabral J, Pietri A, Scott C, Flannery TK, Wilson DB, Rogers B, Campos M, Montero M, Beals B, Mair D, Long A, Rood R, Taylor J, Sevier R, Harris G, Pfeifer M, Blechman M, Giangola J, Creech R, Lathrop M, Dunaif A, Miceli G, Lewy-Alterbaum L, Jellinger P, Novak S, Gellman K, Lerman S, Waxman S, Hamilton D, Driscoll H, Schneier R, Casey J, Boyce P, Meachum J, Milburn J, Pomeroy D, Moll G, Macyko K, Fox L, Mauras N, Ledereich P, Novotney D, Gill C, Rossetto B, Houlden R, Heck P, Korducki J, Winston J, Geffner D, Edelman S, Henry B, Einhorn D, Fink R, Gold E, Calhoun RW, Leidlein J, Arul K, Henry D, Donaldson D, Middlestadt K, Grande-Luke L, Guest J, Wise J, Wermers R, Bells B, Frindik P, Gewirtz G, Blyfeld C, Brakin M, Borut D, Geffner D, Winston J, Geffner M, Rodriguez M, Gura V, Rodriguez M, Shough C, Bays H, Shenouda H, Varma S, Bourgeios M, Sloan L, Guthrow CE, Shaw S, Ruby R, Motzkin-Kava B, Jebsen D, Zador I, Maby S, Crantz F, Zietlow D, Kudzma D, Levy E, Shapiro ET, Jacobi J, Pita J, Abelove W, Perez-Rodriguez J, Gonzalez-Mendoza L, Richton S, Weissman P, Stein N, Sherman-Adcock L, Fergeson D, Jacobson M, Sennett J, Jain R, Etzwiler D, Ramsay R, Holland M, Carrington R, Seagraves S, Yue G, Downs-Colby J, Flores H, Weinrib S, Jones E, Starkman H, White D, Doberne L, Greenfield M, Alexander K, O'Sullivan C, Duncan R, Barandiaran G, Yunis J, Nunez L, Ramos V, Holland E, Balash W, Sher J, Agrin R, Frentz J, Fennoy I, Baron S, Door J, Vinik A, Savery F, Gareis F, Mack R, Devoe D, Fan Y, Domek D, Kelley D, Roberts T, Gutshall B, Madu I, Poucher R, Mengel M, Desrosiers P, Banks R, Kopp B, Fishman I, Geller D, Smith W, Duncan J, Nyman O, Vaccarello-Cruz M, Schwartz F, Olambiwonnu O, Ortiz M, Merrill S, Freedman S, Rezvani I, Doyle D, Hale P, Singer-Granick C, Fore W, Perelman A, Clemmons R, Johnsonbaugh R, Gonzalez A, Baker M, Field C, Shields C, Walker K, Reddy S, Pillote K, Borchelt M, Phillipson B, Bommer D, Curosh N, Karl D, Iverson W, Krosnick A, Kahn C, Blodgett B, Iverson N, Jacobson C, Haynes M, Moore D, Alston R, Eachempati R, Becker D, Weide L, Decker M, Greaves J, Curry M, Radcliffe J, Schauf V, Childs D, Crawford R, Charnogursky G, Stesin M, Schneider M, Rodbard H, Dempsey M, Brummer R, Elston L, Marseters D, Lapp P, Glaser N, Soeldner J, Chaurasia V, Michaels R, King A, Olson R, Hale D, Danney M, Miller S, Madan S, Dudl JR, Bohannon N, Berlund M, Jackson T, Kitzmiller J, Price D, Ehsanipoor K, Homan M, Olshan J, Sorensen T, Perry A, Nepom G, McCulloch D, Hirsch I, Kanter R, Niles N, Vogiatzi M, Kerpe V, McVie R, Aniszewski J, Carroll T, Bacon R, Hudson M, Simpson A, Fili M, Krieger D, Golob D, Carney J, Khardori R, Peitso M, Lane JT, Jensen DF, Katz H, Warhol R, Rothman J, Rooke J, Fogel H, Hotes L, Lilavivat U, Gauthier T, Deeb L, Sherradan T, Lavin N, Shuey K, Horner J, Tsao J, Scrogin A, Greenlee C, Insel J, Wheeler M, Kamal T, Wiertz L, Bucholtz H, Dunn J, Wilson K, Frey M, Noto R, Chochinov R, Bridges JM, Amar M, Weinstein R, Poore TE, Brink S, Moltz K, Sobel D, Francis G, Sveck R, Ramey J, Haque N, Villafria A, Villafria R, Madagame J, Stone L, Cech R, Schnelbach J, Dreidbart S, Noto R, Lebinger T, Shane L, Reece E, Harris R, Welsh W, Whitesides PC, Scoma A, Ziel F, Alter C, Lock P, Treece G.

Abstract

OBJECTIVE:

We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS:

TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity.

RESULTS:

The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons).

CONCLUSIONS:

These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

PMID:
23818528
PMCID:
PMC3747899
DOI:
10.2337/dc13-0425
[Indexed for MEDLINE]
Free PMC Article

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