Dietary Intake and Body Mass Index Influence the Risk of Islet Autoimmunity in Genetically At-Risk Children: A Mediation Analysis Using the TEDDY Cohort

Author:

Andrén Aronsson Carin1ORCID,Tamura Roy2,Vehik Kendra2,Uusitalo Ulla2,Yang Jimin2,Haller Michael J.3,Toppari Jorma45,Hagopian William6,McIndoe Richard A.7,Rewers Marian J.8,Ziegler Anette-G.9,Akolkar Beena10,Krischer Jeffrey P.2,Norris Jill M.11,Virtanen Suvi M.121314,Elding Larsson Helena115ORCID

Affiliation:

1. Department of Clinical Sciences, Lund University, Malmo, Sweden

2. Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

3. University of Florida Diabetes Institute, Gainesville, FL, USA

4. Department of Pediatrics, Turku University Hospital, Turku, Finland

5. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland

6. Pacific Northwest Research Institute, Seattle, WA, USA

7. Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA

8. Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA

9. Institute of Diabetes Research, Helmholtz Zentrum München and Klinikum rechts der Isar, Technische Universität München, Forschergruppe Diabetes e.V, Neuherberg, Germany

10. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

11. Department of Epidemiology, University of Colorado Denver, Colorado School of Public Health, Aurora, CO, USA

12. Finnish Institute for Health and Welfare, Department of Public Health and Welfare, Helsinki, Finland

13. Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland

14. Center for Child Health Research, Tampere University and University Hospital, Tampere, Finland and Research, Development, and Innovation Center, Tampere University Hospital, Tampere, Finland

15. Department of Pediatrics, Skane University Hospital, Malmo, Lund, Sweden

Abstract

Background/Objective. Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods. Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results. We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042 . Conclusions. This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Hindawi Limited

Subject

Endocrinology, Diabetes and Metabolism,Pediatrics, Perinatology and Child Health,Internal Medicine

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