First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study

Abstract

OBJECTIVEStudies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow’s milk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort.RESEARCH DESIGN AND METHODSThe Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D. Autoantibodies to insulin, GAD65, and IA2 were measured regularly to define islet autoimmunity. Information on formula feeding was collected by questionnaires at 3 months of age.RESULTSIn survival analyses, after adjustment for family history with T1D, HLA genotype, sex, country, delivery mode, breast-feeding ≥3 months, and seasonality of birth, we observed no significant association with islet autoimmunity in infants who received extensively hydrolyzed compared with nonhydrolyzed cow’s milk–based formula as the first formula during the first 3 months (adjusted hazard ratio 1.38 [95% CI 0.95; 2.01]), and a significantly increased risk for extensively hydrolyzed formula introduced during the first 7 days (adjusted hazard ratio 1.57 [1.04; 2.38]). Using a partially hydrolyzed or other formula as the first formula, or no formula, was not associated with islet autoimmunity risk.CONCLUSIONSThese results add to the existing evidence that islet autoimmunity risk is not reduced, and may be increased, by using hydrolyzed compared with nonhydrolyzed cow’s milk–based infant formula as the first formula in infants at increased genetic risk for T1D.

The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update

“…Exposure to probiotics in early infancy was found to decrease the risk of IA in the highest risk children [9], while use of hydrolyzed infant formula increased the risk of IA [13]. Intake of soluble fiber is not associated with IA [16].…”

Combination Immunotherapy for Type 1 Diabetes

“…A study of infants with a first-degree relative with T1D found that infants receiving hydrolyzed casein-based formula in place of breast milk were less likely to be positive for two or more autoantibodies, versus infants receiving conventional formula. At study end, no difference in autoantibodies or diabetes incidence was evident seven years post intervention (33, 34). The FINDIA pilot study found that removal of bovine insulin from formula resulted in blunted progression of additional islet autoantibodies three years after intervention compared to conventional cow’s milk formula, supporting the idea of restoration of tolerance.…”

Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study

“…HLA‐DR‐DQ genotype, family history of type 1 diabetes, sex, and country (as a strata) were adjusted in the Cox PH models. Cox PH analysis with additional adjustment for factors previously identified in TEDDY (probiotic introduced before 28 days vs other, type of infant formula during the first 3 months, weight at 12 months, T1D‐related single‐nucleotide polymorphisms (SNPs) [rs2476601 in PTPN22, rs2816316 in RGS1, rs2292239 in ERBB3, rs3184504 in SH2B3, rs4948088 in COBL, rs1004446 in INS, rs1270876 in CLEC16A, rs10517086] and two SNPs in complement genes [rs1143678 and rs4597342 in ITGAM]) were also performed as sensitivity analyses.…”

“…HLA-DR-DQ genotype, family history of type 1 diabetes, sex, and country (as a strata) were adjusted in the Cox PH models. Cox PH analysis with additional adjustment for factors previously identified in TEDDY [24][25][26][27][28] (probiotic introduced before 28 days vs other, type of infant formula during the first 3 months, weight at 12 months, T1D-related single- Table 1.…”