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Early Infant Diet and Islet Autoimmunity in the TEDDY Study.
Diabetes Care ( IF 14.8 ) Pub Date : 2018-01-17 , DOI: 10.2337/dc17-1983 Ulla Uusitalo 1 , Hye-Seung Lee 1 , Carin Andrén Aronsson 2 , Kendra Vehik 1 , Jimin Yang 1 , Sandra Hummel 3 , Katherine Silvis 4 , Åke Lernmark 2 , Marian Rewers 5 , William Hagopian 6 , Jin-Xiong She 4 , Olli Simell 7 , Jorma Toppari 8 , Anette-G. Ziegler 3 , Beena Akolkar 9 , Jeffrey Krischer 1 , Suvi M. Virtanen 10, 11, 12 , Jill M. Norris 13 , Marian Rewers , Kimberly Bautista , Judith Baxter , Ruth Bedoy , Daniel Felipe-Morales , Kimberly Driscoll , Brigitte I. Frohnert , Marisa Gallant , Patricia Gesualdo , Michelle Hoffman , Rachel Karban , Edwin Liu , Jill Norris , Adela Samper-Imaz , Andrea Steck , Kathleen Waugh , Hali Wright , Jorma Toppari , Olli G. Simell , Annika Adamsson , Suvi Ahonen , Heikki Hyöty , Jorma Ilonen , Sanna Jokipuu , Tiina Kallio , Leena Karlsson , Miia Kähönenµ , Mikael Knip , Lea Kovanen , Mirva Koreasalo , Kalle Kurppa , Tiina Latva-aho , Maria Lönnrot , Elina Mäntymäki , Katja Multasuo , Tiina Niininen , Sari Niinistö , Mia Nyblom , Petra Rajala , Jenna Rautanen , Anne Riikonen , Minna Romo , Juulia Rönkä , Satu Simell , Tuula Simell , Maija Sjöberg , Aino Stenius , Maria Leppänen , Sini Vainionpää , Eeva Varjonen , Riitta Veijola , Suvi M. Virtanen , Mari Vähä-Mäkilä , Mari Åkerlund , Katri Lindfors , Jin-Xiong She , Desmond Schatz , Diane Hopkins , Leigh Steed , Jennifer Bryant , Jamie Thomas , Janey Adams , Katherine Silvis , Michael Haller , Melissa Gardiner , Richard McIndoe , Ashok Sharma , Stephen W Anderson , Laura Jacobsen , Anette G. Ziegler , Andreas Beyerlein , Ezio Bonifacio , Anja Heublein , Michael Hummel , Sandra Hummel , Annette Knopff , Charlotte Koch , Sibylle Koletzko , Claudia Ramminger , Roswith Roth , Marlon Scholz , Laura Schulzik , Joanna Stock , Katharina Warncke , Lorena Wendel , Christiane Winkler , Åke Lernmark , Daniel Agardh , Carin Andrén Aronsson , Maria Ask , Jenny Bremer , Ulla-Marie Carlsson , Corrado Cilio , Emelie Ericson-Hallström , Annika Fors , Lina Fransson , Thomas Gard , Rasmus Bennet , Carina Hansson , Susanne Hyberg , Hanna Jisser , Fredrik Johansen , Berglind Jonsdottir , Silvija Jovic , Helena Elding Larsson , Marielle Lindström , Markus Lundgren , Maria Månsson-Martinez , Maria Markan , Jessica Melin , Zeliha Mestan , Caroline Nilsson , Karin Ottosson , Kobra Rahmati , Anita Ramelius , Falastin Salami , Sara Sibthorpe , Anette Sjöberg , Birgitta Sjöberg , Evelyn Tekum Amboh , Carina Törn , Anne Wallin , Åsa Wimar , Sofie Åberg , William A. Hagopian , Michael Killian , Claire Cowen Crouch , Jennifer Skidmore , Ashley Akramoff , Jana Banjanin , Masumeh Chavoshi , Kayleen Dunson , Rachel Hervey , Shana Levenson , Rachel Lyons , Arlene Meyer , Denise Mulenga , Davey Schmitt , Julie Schwabe , Dorothy Becker , Margaret Franciscus , MaryEllen Dalmagro-Elias Smith , Ashi Daftary , Mary Beth Klein , Chrystal Yates , Jeffrey P. Krischer , Sarah Austin-Gonzalez , Maryouri Avendano , Sandra Baethke , Rasheedah Brown , Brant Burkhardt , Martha Butterworth , Joanna Clasen , David Cuthbertson , Christopher Eberhard , Steven Fiske , Dena Garcia , Jennifer Garmeson , Veena Gowda , Kathleen Heyman , Belinda Hsiao , Francisco Perez Laras , Hye-Seung Lee , Shu Liu , Xiang Liu , Kristian Lynch , Colleen Maguire , Jamie Malloy , Cristina McCarthy , Aubrie Merrell , Steven Meulemans , Hemang Parikh , Ryan Quigley , Cassandra Remedios , Chris Shaffer , Laura Smith , Susan Smith , Noah Sulman , Roy Tamura , Ulla Uusitalo , Kendra Vehik , Ponni Vijayakandipan , Keith Wood , Jimin Yang , Michael Abbondondolo , Lori Ballard , David Hadley , Wendy McLeod , Beena Akolkar , Liping Yu , Dongmei Miao , Polly Bingley , Alistair Williams , Kyla Chandler , Claire Williams , Gifty George , Sian Grace , Ben Gillard , William Hagopian , Masumeh Chavoshi , Henry Erlich , Steven J. Mack , Anna Lisa Fear , Sandra Ke , Niveen Mulholland , Kasia Bourcier , Thomas Briese , Suzanne Bennett Johnson , Eric Triplett ,
Diabetes Care ( IF 14.8 ) Pub Date : 2018-01-17 , DOI: 10.2337/dc17-1983 Ulla Uusitalo 1 , Hye-Seung Lee 1 , Carin Andrén Aronsson 2 , Kendra Vehik 1 , Jimin Yang 1 , Sandra Hummel 3 , Katherine Silvis 4 , Åke Lernmark 2 , Marian Rewers 5 , William Hagopian 6 , Jin-Xiong She 4 , Olli Simell 7 , Jorma Toppari 8 , Anette-G. Ziegler 3 , Beena Akolkar 9 , Jeffrey Krischer 1 , Suvi M. Virtanen 10, 11, 12 , Jill M. Norris 13 , Marian Rewers , Kimberly Bautista , Judith Baxter , Ruth Bedoy , Daniel Felipe-Morales , Kimberly Driscoll , Brigitte I. Frohnert , Marisa Gallant , Patricia Gesualdo , Michelle Hoffman , Rachel Karban , Edwin Liu , Jill Norris , Adela Samper-Imaz , Andrea Steck , Kathleen Waugh , Hali Wright , Jorma Toppari , Olli G. Simell , Annika Adamsson , Suvi Ahonen , Heikki Hyöty , Jorma Ilonen , Sanna Jokipuu , Tiina Kallio , Leena Karlsson , Miia Kähönenµ , Mikael Knip , Lea Kovanen , Mirva Koreasalo , Kalle Kurppa , Tiina Latva-aho , Maria Lönnrot , Elina Mäntymäki , Katja Multasuo , Tiina Niininen , Sari Niinistö , Mia Nyblom , Petra Rajala , Jenna Rautanen , Anne Riikonen , Minna Romo , Juulia Rönkä , Satu Simell , Tuula Simell , Maija Sjöberg , Aino Stenius , Maria Leppänen , Sini Vainionpää , Eeva Varjonen , Riitta Veijola , Suvi M. Virtanen , Mari Vähä-Mäkilä , Mari Åkerlund , Katri Lindfors , Jin-Xiong She , Desmond Schatz , Diane Hopkins , Leigh Steed , Jennifer Bryant , Jamie Thomas , Janey Adams , Katherine Silvis , Michael Haller , Melissa Gardiner , Richard McIndoe , Ashok Sharma , Stephen W Anderson , Laura Jacobsen , Anette G. Ziegler , Andreas Beyerlein , Ezio Bonifacio , Anja Heublein , Michael Hummel , Sandra Hummel , Annette Knopff , Charlotte Koch , Sibylle Koletzko , Claudia Ramminger , Roswith Roth , Marlon Scholz , Laura Schulzik , Joanna Stock , Katharina Warncke , Lorena Wendel , Christiane Winkler , Åke Lernmark , Daniel Agardh , Carin Andrén Aronsson , Maria Ask , Jenny Bremer , Ulla-Marie Carlsson , Corrado Cilio , Emelie Ericson-Hallström , Annika Fors , Lina Fransson , Thomas Gard , Rasmus Bennet , Carina Hansson , Susanne Hyberg , Hanna Jisser , Fredrik Johansen , Berglind Jonsdottir , Silvija Jovic , Helena Elding Larsson , Marielle Lindström , Markus Lundgren , Maria Månsson-Martinez , Maria Markan , Jessica Melin , Zeliha Mestan , Caroline Nilsson , Karin Ottosson , Kobra Rahmati , Anita Ramelius , Falastin Salami , Sara Sibthorpe , Anette Sjöberg , Birgitta Sjöberg , Evelyn Tekum Amboh , Carina Törn , Anne Wallin , Åsa Wimar , Sofie Åberg , William A. Hagopian , Michael Killian , Claire Cowen Crouch , Jennifer Skidmore , Ashley Akramoff , Jana Banjanin , Masumeh Chavoshi , Kayleen Dunson , Rachel Hervey , Shana Levenson , Rachel Lyons , Arlene Meyer , Denise Mulenga , Davey Schmitt , Julie Schwabe , Dorothy Becker , Margaret Franciscus , MaryEllen Dalmagro-Elias Smith , Ashi Daftary , Mary Beth Klein , Chrystal Yates , Jeffrey P. Krischer , Sarah Austin-Gonzalez , Maryouri Avendano , Sandra Baethke , Rasheedah Brown , Brant Burkhardt , Martha Butterworth , Joanna Clasen , David Cuthbertson , Christopher Eberhard , Steven Fiske , Dena Garcia , Jennifer Garmeson , Veena Gowda , Kathleen Heyman , Belinda Hsiao , Francisco Perez Laras , Hye-Seung Lee , Shu Liu , Xiang Liu , Kristian Lynch , Colleen Maguire , Jamie Malloy , Cristina McCarthy , Aubrie Merrell , Steven Meulemans , Hemang Parikh , Ryan Quigley , Cassandra Remedios , Chris Shaffer , Laura Smith , Susan Smith , Noah Sulman , Roy Tamura , Ulla Uusitalo , Kendra Vehik , Ponni Vijayakandipan , Keith Wood , Jimin Yang , Michael Abbondondolo , Lori Ballard , David Hadley , Wendy McLeod , Beena Akolkar , Liping Yu , Dongmei Miao , Polly Bingley , Alistair Williams , Kyla Chandler , Claire Williams , Gifty George , Sian Grace , Ben Gillard , William Hagopian , Masumeh Chavoshi , Henry Erlich , Steven J. Mack , Anna Lisa Fear , Sandra Ke , Niveen Mulholland , Kasia Bourcier , Thomas Briese , Suzanne Bennett Johnson , Eric Triplett ,
Affiliation
OBJECTIVE
To examine duration of breastfeeding and timing of complementary foods and risk of islet autoimmunity (IA).
RESEARCH DESIGN AND METHODS
The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes (T1D) in the U.S., Finland, Germany, and Sweden. This study included 7,563 children with at least 9 months of follow-up. Blood samples were collected every 3 months from birth to evaluate IA, defined as persistent, confirmed positive antibodies to insulin (IAAs), GAD, or insulinoma antigen-2. We examined the associations between diet and the risk of IA using Cox regression models adjusted for country, T1D family history, HLA genotype, sex, and early probiotic exposure. Additionally, we investigated martingale residuals and log-rank statistics to determine cut points for ages of dietary exposures.
RESULTS
Later introduction of gluten was associated with increased risk of any IA and IAA. The hazard ratios (HRs) for every 1-month delay in gluten introduction were 1.05 (95% CI 1.01, 1.10; P = 0.02) and 1.08 (95% CI 1.00, 1.16; P = 0.04), respectively. Martingale residual analysis suggested that the age at gluten introduction could be grouped as <4, 4-9, and >9 months. The risk of IA associated with introducing gluten before 4 months of age was lower (HR 0.68; 95% CI 0.47, 0.99), and the risk of IA associated with introducing it later than the age of 9 months was higher (HR 1.57; 95% CI 1.07, 2.31) than introduction between 4 and 9 months of age.
CONCLUSIONS
The timing of gluten-containing cereals and IA should be studied further.
中文翻译：
TEDDY 研究中的早期婴儿饮食和胰岛自身免疫。
目的 检查母乳喂养的持续时间和补充食品的时间以及胰岛自身免疫 (IA) 的风险。研究设计和方法 青少年糖尿病环境决定因素 (TEDDY) 研究前瞻性地跟踪了美国、芬兰、德国和瑞典 8,676 名 1 型糖尿病 (T1D) 遗传风险增加的儿童。这项研究包括 7,563 名儿童，并进行了至少 9 个月的随访。从出生起每 3 个月采集一次血样以评估 IA，IA 定义为持续、确认的胰岛素阳性抗体 (IAA)、GAD 或胰岛素瘤抗原 2。我们使用 Cox 回归模型检查了饮食与 IA 风险之间的关联，并根据国家、T1D 家族史、HLA 基因型、性别和早期益生菌暴露进行了调整。此外，我们还研究了鞅残差和对数秩统计，以确定饮食暴露年龄的切点。结果 较晚引入麸质与任何 IA 和 IAA 的风险增加相关。引入麸质每延迟 1 个月，风险比 (HR) 分别为 1.05 (95% CI 1.01, 1.10; P = 0.02) 和 1.08 (95% CI 1.00, 1.16; P = 0.04)。 Martingale 残差分析表明，引入麸质的年龄可分为 <4、4-9 和 >9 个月。 4 月龄之前引入麸质相关的 IA 风险较低（HR 0.68；95% CI 0.47，0.99），而 9 月龄之后引入麸质相关的 IA 风险较高（HR 1.57；95）。 % CI 1.07, 2.31) 与 4 至 9 个月龄之间引入相比。结论 应进一步研究含麸质谷物和 IA 的时机。
更新日期：2018-02-21
中文翻译：
TEDDY 研究中的早期婴儿饮食和胰岛自身免疫。
目的 检查母乳喂养的持续时间和补充食品的时间以及胰岛自身免疫 (IA) 的风险。研究设计和方法 青少年糖尿病环境决定因素 (TEDDY) 研究前瞻性地跟踪了美国、芬兰、德国和瑞典 8,676 名 1 型糖尿病 (T1D) 遗传风险增加的儿童。这项研究包括 7,563 名儿童，并进行了至少 9 个月的随访。从出生起每 3 个月采集一次血样以评估 IA，IA 定义为持续、确认的胰岛素阳性抗体 (IAA)、GAD 或胰岛素瘤抗原 2。我们使用 Cox 回归模型检查了饮食与 IA 风险之间的关联，并根据国家、T1D 家族史、HLA 基因型、性别和早期益生菌暴露进行了调整。此外，我们还研究了鞅残差和对数秩统计，以确定饮食暴露年龄的切点。结果 较晚引入麸质与任何 IA 和 IAA 的风险增加相关。引入麸质每延迟 1 个月，风险比 (HR) 分别为 1.05 (95% CI 1.01, 1.10; P = 0.02) 和 1.08 (95% CI 1.00, 1.16; P = 0.04)。 Martingale 残差分析表明，引入麸质的年龄可分为 <4、4-9 和 >9 个月。 4 月龄之前引入麸质相关的 IA 风险较低（HR 0.68；95% CI 0.47，0.99），而 9 月龄之后引入麸质相关的 IA 风险较高（HR 1.57；95）。 % CI 1.07, 2.31) 与 4 至 9 个月龄之间引入相比。结论 应进一步研究含麸质谷物和 IA 的时机。
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