Format

Send to:

Choose Destination
See comment in PubMed Commons below
JAMA. 2014 Jun 11;311(22):2279-87. doi: 10.1001/jama.2014.5610.

Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial.

Collaborators (647)

Mandrup-Poulsen T, Arjas E, Lernmark Å, Läärä E, Schmidt B, Krischer JP, Åkerblom HK, Hyytinen M, Knip M, Koski K, Koski M, Merentie K, Pajakkala E, Reunanen A, Salonen M, Terhonen T, Virkkunen S, Cuthbertson D, Gainer B, Hadley D, Krischer JP, Malloy J, Nallamshetty L, Shanker L, Bradley B, Dupré J, Lough G, Nielsen D, Fraser W, Lawson ML, Mahon JL, Sermer M, Taback SP, Becker D, Franciscus M, Nucci A, Palmer J, Alahuhta K, Bärlund S, Korhonen T, Lehtonen E, Pekkala M, Sorkio S, Vähätalo L, Virtanen SM, Uusitalo U, Öhman T, Bongiorno R, Catteau J, Fraser G, Howard N, Lloyd M, Crock P, Giles M, Siech K, Wong SD, Brown C, Catteau J, Craig M, Johnston A, Bere LJ, Clarson CL, Jenner M, Mahon JL, McManus R, Renato N, Higo D, Kent N, Kozak S, Kwan J, Marshall C, Metzger D, Stewart L, Taylor C, Thompson D, Tong SO, Edwards A, Lange I, Mercer J, Pacaud D, Schwarz W, Stephure DK, Swaby C, Baergen-Fladager S, Boer J, Chatur T, Chick C, Couch B, Demianczuk N, Girgis R, Marks S, Ryan E, Thompson M, Berard L, Bloomfield E, Catte D, Dean HJ, Grant L, Hamelin K, LaForte J, Murphy L, Schneider C, Sellers EA, Taback SP, Woo V, Boland A, Bradley B, Clark HD, Cooper T, Cormier R, Frederick C, Good M, Gruslin A, Kane D, Karovitch A, Keely E, Lawson ML, Lough G, Malcolm JC, O'Shea E, Ranieri M, Rouatt S, Sauro V, Tawagi GF, Andrighetti S, Aquilina A, Arnold G, Barrett J, Bartley C, Blumer I, Brush C, Daneman D, Denis D, Ehrlich R, Feig D, Gherson B, Gottesman I, Gysler M, Karkanis S, Kenshole A, Knight B, Lackie E, Lewis V, Martin MJ, Maxwell C, McLeod L, Oliver G, Panchum P, Sermer M, Shilletto N, Simone A, Skidmore M, Turrini T, Wong S, Allen C, Bélanger L, Bouchard I, Chapdelaine M, Ferland S, Frenette L, Garrido-Russo M, Latulippe D, Leblanc M, Imbeault J, Marc I, Morin V, Olivier G, Weisnagell J, Costain G, Dornan J, Heath K, MacSween MC, McGibbon A, Ramsay C, Sanderson F, Sanderson S, Anctil C, Benabdesselam L, Fraser W, Gonthier M, Huot C, Lagace M, Lortie L, Roy C, Thibeault M, Diotalevi S, Gagné V, Laforte D, Legault L, Perron P, Armson A, Canning P, Cummings EA, Hardie R, Ivanko V, McLeod L, McPhee A, Mokashi A, Morrison L, Scott K, Bridger T, Crane J, Crummell C, Curtis JC, Dawson C, Grant M, Joyce C, Newhook LA, Begum-Hasan J, Breen A, Chambers B, Houlden R, Woods M, Carrson G, Kelly S, Andreychuk B, Martel MJ, Penner M, Sankaran K, Burnie S, Hardy-Brown K, King N, White RA, Park M, Peters D, Popkin J, Robson L, Al Taji E, Aldhoon A, Cerna M, Cerny M, Francova H, Hainerova I, Kothankova H, Koukalova R, Krakorova V, Mendlova P, Romanova M, Sitova R, Stechova K, Katerina J, Vosahlo J, Zlatohlavkova B, Brazdova L, Faksova P, Gregorova D, Kantor L, Malkova K, Venhacova J, Venhacova P, Cipra A, Skvor J, Tomsikova Z, Botkova-Krauseova H, Mockova A, Krckova P, Gogelova P, Kandrnalova J, Einberg Ü, Jakovlev Ü, Krassotkina S, Rannaste E, Raukas R, Riikjärv MA, Mark K, Astover V, Kirss A, Ormisson A, Retpap J, Täht E, Tillmann V, Vahtra S, Åkerblom HK, Heikkilä M, Luopajärvi K, Kleemola P, Knip M, Laukkanen E, Parkkola A, Pigg HM, Puttonen H, Renlund M, Suomalainen H, Tenkula T, Teramo K, Järvenpää AL, Hämälainen AM, Jussila R, Haavisto H, Holopainen S, Kupiainen H, Leeve T, Nironen T, Tenhola S, Tiilikainen T, Keinonen H, Lautala P, Salonen P, Vesanto M, Aspholm AS, Asunta P, Ikävalko H, Jäminki S, Kekki P, Koskinen M, Lehtimäki S, Lähde J, Mäkelä M, Peltoniemi S, Poutiainen L, Ranta K, Salonsaari T, Sarviharju-Tujula SL, Siljander H, Haanpaa PL, Holm C, Järveläinen V, Kangaskolkka-Keskilohko AM, Laino E, Marjamäki L, Suominen E, Ylitalo S, Hokkanen M, Lounamaa R, Matikainen M, Nuuja A, Puupponen AR, Salo-Edwards H, Alanne S, Kultti T, Linjama H, Muhonen K, Sauna-aho M, Talvitie T, Backman M, Hanhijärvi R, Koivula P, Lehtomäki S, Muikku E, Pesola J, Sankilampi U, Arkkola T, Hekkala A, Jurvakainen S, Koivikko ML, Kähönen M, Leinonen E, Mykkänen H, Riikonen K, Niittyvuopio A, Stenius A, Tapanainen P, Veijola R, Alar A, Jovio S, Korpela P, Mäkinen E, Hietanen L, Kivistö J, Käär ML, Lehtimäki P, Mustila T, Popov E, Säätelä S, Taittonen L, Ahtiainen K, Laaksonen N, Luoto M, Viitala J, Virransalo R, Nykänen P, Paajanen S, Parkkinen S, Pyrhönen H, Särkkä T, Aschemeier B, Bektas S, Danne T, Datz N, Deiss D, Kordonouri O, Lüpke K, Müller B, Nestoris C, Rothes S, Sadeghian E, Semler K, Arató A, Krikovszky D, Madácsy L, Nobilis A, Szénási J, Benevento D, Beretta Anguissola G, Biagioni M, Bizzarri C, Cherubini V, Giordano C, Giorgetti C, Khazrai YM, Kyanvash S, Maddaloni E, Napoli A, Piergiovanni F, Pitocco D, Pozzilli P, Suraci T, Valente L, Visalli N, Carboni MB, Casu A, Cavallo R, Cau V, Isola C, Ledda A, Loddo M, Mannu C, Pettinau M, Pisano S, Porceddu M, Putzu C, Rita A, Songini M, de Beaufort C, Peters D, Schierloh U, Bruining J, Bisschoff M, Blonk L, Lappenschaar T, Manai B, Maaike S, Sperling-Conrad M, Verhagen M, Zoethout JA, Basiak A, Chalas M, Chesiak M, Gramza A, Iwankiewicz J, Sieradzan E, Wasikowa R, Wikiera B, Ciechanowska M, Dziatkowiak H, Futona B, Górska A, Glowacka-Woźny M, Kaim I, Klich B, Starzyk J, Styrna M, Tokarska L, Chucherco D, Deja G, Firek-Pedras M, Jarosz-Chobot P, Kalina M, Kutrowska-Adamusiak K, Minkina-Pedras M, Muchacka-Bianga M, Bodalski J, Mlynarski W, Szadkowska A, Cieslak A, Cypryk K, Dziatosz K, Jastzebowska J, Krysiak A, Szymanska U, Wilczyñski J, Zawodniak-Szalapska M, Aguayo A, Bilbao JR, Castano L, Chueca M, Cortazar A, Echarte G, Gonzalez Frutos T, Jimenez P, Martul P, Moreno A, Oyarzabal M, Rica I, Salgado Y, Serrano-Ríos M, Martínez-Larrad MT, Hawkins FG, Herranz L, Pallardo LF, Saez de Ibarra L, Huidobro Fernandez B, Leon Luis J, Ortíz-Quintana L, Pintado Recarte P, Rodriguez Arnau D, Aronsson L, Bodén S, Fredriksson J, Isacsson E, Johansson I, Karlsson E, Lock C, Ludvigsson J, Sandström AM, Smolinska Konefal M, Andreasson C, Dahlström U, Hanas R, Lundqvist K, Windell L, Jansson I, Karlsson AK, Lindbladh B, Odenman I, Pettersson C, Sundqvist M, Aronsson S, Bellman I, Bengtsson AB, Lydén GB, Nilsson NÖ, Söderblom M, Unt C, Bengtsson M, Fors H, Helmrich A, Osland Johansson T, Andersson AC, Hellgren G, Källsholm H, Lindqvist J, Nilsson M, Nordwall M, Åhsberg C, Lindh A, Lindhe C, Samuelsson C, Wiik A, Edenwall H, Persson IB, Strigard E, Svensson BL, Åman J, Breivik GE, Detlofsson IL, Kroon M, Johansson C, Ilvered R, Lundberg A, Åkesson K, Beccarelli A, Gadient M, Rappold-Amrein C, Schoenle E, Becker D, Daftary A, Damagro-Elias ME, Franciscus M, Gilmour C, Klein MB, Lain C, Salerno D, Smith ME, Vats K, Jones Pfaff D, Malone P, Mansfield P, Munns M, Nickel K, Palmer J, Pompilio K, Siemion W, Taculad R, Van Horn K, Zdanadewic M, Chambliss C, Jones J, Sadler M, Tanner-Blasiar M, White N, Bell C, Camper N, Devaskar S, Devaskar U, Horowitz H, Rogers L, Shannahan R, Silk K, Bermudez Z, Colon R, Frazer T, Martinez-Nieves B, Torres J, Vega J, Chan M, Cook S, Goland R, Greenberg E, Jules N, Montes J, Nelson M, Schachner H, Softness B, Ilonen J, Kiviniemi M, Suominen R, Alexander A, Hyrckowian E, Nichol L, Stefura C, Trucco M, Karjalainen E, Louhio T, Sarnesto A, Savilahti E, Valtonen E, Davydova B, Helander S, Hämäläinen J, Härkönen T, Joutsjoki L, Kararic M, Knip M, Latva-Koivisto M, Lönn E, Nurmi T, Ollila I, Rinkinen J, Ronkainen M, Tukiainen H, Cederlöf A, Kiikeri M, Luopajärvi K, Tsupari S, Vaarala O, Cheung R, Bryant K, Chan Y, Dosch HM, Maezawa Y, Paltser G, Rasavi R, Tsui H, Winer S, Wu P, Yantha J.

Abstract

IMPORTANCE:

The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.

OBJECTIVE:

To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.

DESIGN, SETTING, AND PARTICIPANTS:

A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.

INTERVENTIONS:

The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.

MAIN OUTCOMES:

AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).

RESULTS:

The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.

CONCLUSIONS AND RELEVANCE:

Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.

PMID:
24915259
[PubMed - indexed for MEDLINE]
PMCID:
PMC4225544
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Write to the Help Desk