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. 2026 Jul;42(5):e70196.
doi: 10.1002/dmrr.70196.

Retinol, Carotenoid, and Tocopherol Intake and Status, and the Risk of Islet Autoimmunity and Type 1 Diabetes: The Environmental Determinants of Diabetes in the Young Study

Leena Hakola  1   2   3 , Joanna L Clasen  4 , Ulla Uusitalo  4 , Carin Andrén Aronsson  5   6 , Sandra Hummel  7 , Markus Mattila  1   2 , Sari Niinistö  3 , Jorma Toppari  8   9 , Anette-G Ziegler  7 , William A Hagopian  10 , Beena Akolkar  11 , Marian J Rewers  12 , Richard A McIndoe  13 , Åke Lernmark  5 , Jeffrey P Krischer  4 , Jill M Norris  14 , Iris Erlund  15 , Suvi M Virtanen  1   2   3   16   17 ; TEDDY Study Group
Affiliations

Retinol, Carotenoid, and Tocopherol Intake and Status, and the Risk of Islet Autoimmunity and Type 1 Diabetes: The Environmental Determinants of Diabetes in the Young Study

Leena Hakola et al. Diabetes Metab Res Rev. 2026 Jul.

Abstract

Aims: To study the associations of dietary intake of A and E vitamins, as well as plasma retinols, carotenoids, and tocopherols in relation to development of islet autoimmunity and progression to T1D.

Materials and methods: The Environmental Determinants of Diabetes in the Young (TEDDY) Study followed 7659 newborns with genetic susceptibility to T1D for 6 years in the USA, Finland, Germany, and Sweden. Dietary vitamin intake was assessed repeatedly with 3-day food-records in full cohort at ages 6 months to 6 years. Plasma retinols, carotenoids, and tocopherols were analysed in a nested case-control setting with 359 children with islet autoimmunity and 1033 matched controls.

Results: In the full cohort analyses, dietary intake of retinol, β-carotene, and vitamin E was not associated with the risk of islet autoimmunity or progression to T1D. Further, none of the plasma retinol, carotenoid, and tocopherol biomarkers were associated with islet autoimmunity or T1D in the full nested case-control analyses. We observed effect modification by country, breastfeeding, sex, and follow-up time for both intake and biomarkers of vitamins on the risk of islet autoimmunity or T1D, and some subgroup associations. Finally, a plasma carotenoid metabolite (likely zeinoxanthin) (OR 0.61, 95% CI 0.39, 0.95, p = 0.03) and γ-carotene at 6 months (OR 0.65, 95% CI 0.45, 0.94, p = 0.02) were inversely associated with the odds of developing GADA-first.

Conclusions: Retinol, carotenoids and tocopherols were not consistently associated with islet autoimmunity. This study adds to the understanding of factors and their interactions related to T1D development.

Keywords: birth cohort; carotenoids; diabetes mellitus, type 1; retinol; tocopherols; vitamin A; vitamin E.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Adjusted associations between plasma retinol, carotenoids, and tocopherols and risk of islet autoimmunity (A) and type 1 diabetes (T1D) (B) in children aged 6 months to 6 years, the TEDDY nested case‐control study. Biomarkers were modelled as mean of all visits before islet autoimmunity, and at 6 months of age. Mean models include 359 matched sets for islet autoimmunity and 104 for T1D; 6‐month models include 285 for islet autoimmunity and 81 for T1D. Islet autoimmunity and persistent confirmed islet autoimmunity to at least autoantibody. Control children were matched for FDR, clinical centre, and sex. OR (95% CI, confidence interval) were based on conditional logistic regression ran separately for each biomarker. Adjusted for HLA‐DR3/4 genotype (yes, no), breastfeeding at 6 months (yes, no), and cholesterol. C2 (likely lutein metabolite), C6 (likely rubixanthin), and C7 (likely zeinoxanthin) are minor carotenoids/carotenoid metabolites.
FIGURE 2
FIGURE 2
Adjusted associations between plasma retinols, carotenoids, and tocopherols and risk of IAA‐first (A) and GADA‐first (B) islet autoimmunity in children aged 6 months to 6 years, the TEDDY nested case‐control study. The number of IAA‐first cases/controls was 172/485 in mean models and 144/381 in 6‐month models. Respective numbers for GADA‐first are 120/354 and 90/249. Control children were matched for FDR, clinical centre, and sex. OR (95% CI, confidence interval) were based on conditional logistic regression ran separately for each biomarker. Adjusted for HLA‐DR3/4 genotype (yes, no), breastfeeding at 6 months (yes, no), and cholesterol. Biomarkers were modelled as means of all visits before islet autoimmunity, and at 6 months of age. C2 (likely lutein metabolite), C6 (likely rubixanthin), and C7 (likely zeinoxanthin) are minor carotenoids/carotenoid metabolites.
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