Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in DenmarkBMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3547 (Published 19 September 2018) Cite this as: BMJ 2018;362:k3547
- Julie C Antvorskov, assistant professor1,
- Thorhallur I Halldorsson, professor in food science and nutrition2 3 4,
- Knud Josefsen, senior researcher1,
- Jannet Svensson, associate professor5,
- Charlotta Granström, statistician2,
- Bart O Roep, professor6 7,
- Trine H Olesen, research assistant2,
- Laufey Hrolfsdottir, director8,
- Karsten Buschard, professor1,
- Sjudur F Olsen, adjunct professor of nutrition2 9
- 1Bartholin Institute, Rigshospitalet, Ole Måløes Vej 5, 2200 Copenhagen K, Denmark
- 2Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
- 3Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland
- 4Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
- 5Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Children and Adolescents, Copenhagen University Hospital Herlev, Herlev, Denmark
- 6Department of Diabetes Immunology, Diabetes and Metabolism Research Institute at the Beckman Diabetes Research Institute, City of Hope, Duarte, CA, USA
- 7Departments of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands
- 8Department of Education, Science, and Quality, Akureyri Hospital, Akureyri, Iceland
- 9Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Correspondence to: K Josefsen
- Accepted 26 July 2018
Objective To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans.
Design National prospective cohort study.
Setting National health information registries in Denmark.
Participants Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002,
Main outcome measures Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants’ children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes.
Results The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)).
Conclusions High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.
Contributors: JCA initiated the study. SFO was responsible for the data collection. TIH, CG, THO, LH, and SFO were responsible for the dietary database within the Danish National Birth Cohort, including quantification of gluten intake, and JS for type 1 diabetes case validation. TIH and LH carried out the statistical analyses. JCA and TIH drafted the work. JCA, TIH, and KJ wrote the final version of the manuscript. All authors participated in the interpretation of the results as well as revision of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. TIH, CG, THO, and SFO had full access to the server where data were kept. Access by other authors was granted under supervision of those with who had direct access to data. JCA is the guarantor.
Funding: This study was supported by Kirsten and Freddy Johansens Foundation, and by the March of Dimes Foundation (6-FY-96-0240, 6-FY97-0553, 6-FY97-0521, 6-FY00-407), Innovation Fund Denmark (grant No 09-067124, Centre for Fetal Programming), Danish Heart Association, Sygekassernes Helsefond, and the Danish National Research Foundation. The funders had no influence on the study.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Kirsten and Freddy Johansens Foundation, March of Dimes Foundation, Innovation Fund Denmark, Danish Heart Association, Sygekassernes Helsefond, and the Danish National Research Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Data collection in the Danish National Birth Cohort was approved by the Danish National Ethics Board, and all participants provided written informed consent.
Data sharing: Computer codes for the statistical analyses are available on request. The data underlying the presented results in this paper can be shared by sending a request via the regular mechanism for obtaining access to data from the Danish National Birth Cohort (https://www.ssi.dk/English/RandD/Research%20areas/Epidemiology/DNBC/For%20researchers/How%20to%20apply%20for%20data.aspx).
The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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