PuSH - Publikationsserver des Helmholtz Zentrums München: Dietary intake and body mass index influence the risk of islet autoimmunity in genetically at-risk children: A mediation analysis using the TEDDY Cohort.

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Aronsson, C.A.* ; Tamura, R.* ; Vehik, K.* ; Uusitalo, U.* ; Yang, J.* ; Haller, M.J.* ; Toppari, J.* ; Hagopian, W.* ; McIndoe, R.A.* ; Rewers, M.J.* ; Ziegler, A.-G. ; Akolkar, B.* ; Krischer, J.P.* ; Norris, J.M.* ; Virtanen, S.M.* ; Larsson, H.E.*

Dietary intake and body mass index influence the risk of islet autoimmunity in genetically at-risk children: A mediation analysis using the TEDDY Cohort.

Pediatr. Diabetes 2023:11 (2023)

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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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