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

Aronsson, Carin Andrén LU orcid ; Tamura, Roy ; Vehik, Kendra LU ; Uusitalo, Ulla ; Yang, Jimin ; Haller, Michael J. ; Toppari, Jorma ; Hagopian, William ; McIndoe, Richard A. and Rewers, Marian J. , et al. (2023) In Pediatric Diabetes 2023.
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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Diabetes
volume
2023
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:37614409
  • scopus:85168618367
ISSN
1399-543X
DOI
10.1155/2023/3945064
language
English
LU publication?
yes
id
d7ba4a7c-e8da-4a9c-b698-403fb80aee1c
date added to LUP
2023-11-10 13:43:09
date last changed
2025-03-25 15:26:51
@article{d7ba4a7c-e8da-4a9c-b698-403fb80aee1c,
  abstract     = {{<p>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.</p>}},
  author       = {{Aronsson, Carin Andrén and Tamura, Roy and Vehik, Kendra and Uusitalo, Ulla and Yang, Jimin and Haller, Michael J. and Toppari, Jorma and Hagopian, William and McIndoe, Richard A. and Rewers, Marian J. and Ziegler, Anette G. and Akolkar, Beena and Krischer, Jeffrey P. and Norris, Jill M. and Virtanen, Suvi M. and Larsson, Helena Elding}},
  issn         = {{1399-543X}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Pediatric Diabetes}},
  title        = {{Dietary Intake and Body Mass Index Influence the Risk of Islet Autoimmunity in Genetically At-Risk Children : A Mediation Analysis Using the TEDDY Cohort}},
  url          = {{http://dx.doi.org/10.1155/2023/3945064}},
  doi          = {{10.1155/2023/3945064}},
  volume       = {{2023}},
  year         = {{2023}},
}