Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial

TRIGR Study Group

doi:10.1001/jama.2017.19826

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial

TRIGR Study Group

Inflammation, Metabolism and Oxidation

56 Citationer (Scopus)

Abstract

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.

Originalsprog	Engelsk
Tidsskrift	J A M A: The Journal of the American Medical Association
Vol/bind	319
Udgave nummer	1
Sider (fra-til)	38-48
ISSN	0098-7484
DOI	https://doi.org/10.1001/jama.2017.19826
Status	Udgivet - 2 jan. 2018

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10.1001/jama.2017.19826

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@article{221db57d60dc48ada4b53f8589fbadff,

title = "Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial",

abstract = "IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.",

author = "Mikael Knip and {\AA}kerblom, {Hans K.} and {Al Taji}, Eva and Dorothy Becker and Jan Bruining and Luis Castano and Thomas Danne and {De Beaufort}, Carine and Hans-michael Dosch and John Dupre and Fraser, {William D.} and Neville Howard and Jorma Ilonen and Daniel Konrad and Olga Kordonouri and Krischer, {Jeffrey P.} and Lawson, {Margaret L.} and Johnny Ludvigsson and Laszlo Madacsy and Mahon, {Jeffrey L.} and Anne Ormisson and Palmer, {Jerry P.} and Paolo Pozzilli and Erkki Savilahti and Manuel Serrano-rios and Marco Songini and Shayne Taback and Outi Vaarala and White, {Neil H.} and Virtanen, {Suvi M.} and Renata Wasikowa and Thomas Mandrup-Poulsen and {TRIGR Study Group}",

year = "2018",

month = jan,

day = "2",

doi = "10.1001/jama.2017.19826",

language = "English",

volume = "319",

pages = "38--48",

journal = "J A M A: The Journal of the American Medical Association",

issn = "0098-7484",

publisher = "American Medical Association",

number = "1",

}

TY - JOUR

T1 - Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes

T2 - The TRIGR Randomized Clinical Trial

AU - Knip, Mikael

AU - Åkerblom, Hans K.

AU - Al Taji, Eva

AU - Becker, Dorothy

AU - Bruining, Jan

AU - Castano, Luis

AU - Danne, Thomas

AU - De Beaufort, Carine

AU - Dosch, Hans-michael

AU - Dupre, John

AU - Fraser, William D.

AU - Howard, Neville

AU - Ilonen, Jorma

AU - Konrad, Daniel

AU - Kordonouri, Olga

AU - Krischer, Jeffrey P.

AU - Lawson, Margaret L.

AU - Ludvigsson, Johnny

AU - Madacsy, Laszlo

AU - Mahon, Jeffrey L.

AU - Ormisson, Anne

AU - Palmer, Jerry P.

AU - Pozzilli, Paolo

AU - Savilahti, Erkki

AU - Serrano-rios, Manuel

AU - Songini, Marco

AU - Taback, Shayne

AU - Vaarala, Outi

AU - White, Neil H.

AU - Virtanen, Suvi M.

AU - Wasikowa, Renata

AU - Mandrup-Poulsen, Thomas

AU - TRIGR Study Group

PY - 2018/1/2

Y1 - 2018/1/2

N2 - IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.

AB - IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes.

U2 - 10.1001/jama.2017.19826

DO - 10.1001/jama.2017.19826

M3 - Journal article

C2 - 29297078

SN - 0098-7484

VL - 319

SP - 38

EP - 48

JO - J A M A: The Journal of the American Medical Association

JF - J A M A: The Journal of the American Medical Association

IS - 1

ER -

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial

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