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

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.

Low-Protein Infant Formula Enriched with Alpha-Lactalbumin during Early Infancy May Reduce Insulin Resistance at 12 Months: A Follow-Up of a Randomized Controlled Trial

“…Accelerated weight gain during childhood, particularly during the first two years of life, has been linked to the development of auto-antibodies to pancreatic beta-cells, a first sign of the autoimmune process leading to clinical type 1 diabetes in genetically predisposed children [42,43]. Furthermore, associations have recently been found between high protein-energy intake in early childhood and increased risk of developing a specific type of auto-antibody to pancreatic beta-cells (GAD65) in children at risk of developing type 1 diabetes [44]. The precise mechanism behind this association is yet to be clarified, but protein-induced high BCAA concentrations with subsequently high insulin and IGF-1 levels are likely to be involved in the process.…”

Presence of Type 1 Diabetes-Related Autoantibodies in Pediatric Population in Bosnia and Herzegovina

“…The presence of GAD and IA-2 are associated with older age, and GAD additionally with female gender ( 7 ). Autoantibodies can appear very early in life, and the order of appearance is related to genotype ( 8 ).…”