Metabolomics and lipid-related dietary patterns in the development of islet autoimmunity: The Environmental Determinants of Diabetes in the Young

Introduction

The role of diet in type 1 diabetes (T1DM) development is poorly understood, perhaps due to differences in biological processing of nutrition. Metabolites, which mark response to diet, in combination with reported intake may help elucidate this role. Therefore, we examined the association of metabolomics and metabolite-related dietary patterns with islet autoimmunity (IA) in The Environmental Determinants of Diabetes in the Young (TEDDY).

Methods

TEDDY follows 8,676 children at high genetic-risk for T1DM. IA is defined by repeated positivity for at least one autoantibody (IAA, GADA, IA-2A). Secondary outcomes include IAA or GADA as first-appearing autoantibody, or multiple autoantibodies (mAb+). IA children identified by May 2012 were matched to controls using risk set sampling. The association of 853 untargeted plasma metabolites with outcomes were tested at 9-months, using conditional logistic regression adjusted for age at blood draw and high-risk HLA genotype. Individual associations were grouped into enriched metabolite sets using ChemRICH. Reported intake from 3-day food records was combined into 20 food groups. Dietary patterns explaining variation in key metabolites from enriched sets were created using reduced rank regression, and tested for association with outcomes using multivariable conditional logistic regression.

Results

infancy, 7.5% of metabolites significantly differed between IA children and controls (nominal-p<0.05); more (15%) differed when restricting to mAb+ cases. Chemically similar sets of unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, galactosylceramides, and phospholipid ethers were inversely associated with mAb+ risk, while dicarboxylic acids increased risk (adjusted-p<0.05). A dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower levels of sphingomyelins was protective for mAb+ (OR=0.67[95%CI=0.48-0.96]). This lipid-related dietary pattern corresponded to decreased intake of dried fruits, legumes, and infant formula, and increased intake of breast milk, red meat, potatoes, and cereals.

Conclusion

The risk for mAb+ decreased by metabolomics factors, possibly by changes in lipid-related dietary intake.