Randi K Johnson1,2, Lauren A Vanderlinden3, Brian C DeFelice4, Ulla Uusitalo5, Jennifer Seifert1, Sili Fan4, Tessa Crume1, Oliver Fiehn4, Marian Rewers6, Katerina Kechris3, Jill M Norris1. 1. Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 2. Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 3. Department of Biostatistics & Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 4. UC Davis Genome Center-Metabolomics, University of California Davis, Davis, California, USA. 5. Health Informatics Institute, University of South Florida College of Medicine, Tampa, Florida, USA. 6. Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Abstract
OBJECTIVE: Our aim was to elucidate the role of diet in type 1 diabetes (T1D) by examining combinations of nutrient intake in the progression from islet autoimmunity (IA) to T1D. METHODS: We measured 2457 metabolites and dietary intake at the time of seroconversion in 132 IA-positive children in the prospective Diabetes Autoimmunity Study in the Young. IA was defined as the first of two consecutive visits positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). By December 2018, 40 children progressed to T1D. Intakes of 38 nutrients were estimated from semiquantitative food frequency questionnaires. We tested the association of each metabolite with progression to T1D using multivariable Cox regression. Nutrient patterns that best explained variation in candidate metabolites were identified using reduced rank regression (RRR), and their association with progression to T1D was tested using Cox regression adjusting for age at seroconversion and high-risk HLA genotype. RESULTS: In stepwise selection, 22 nutrients significantly predicted at least two of the 13 most significant metabolites associated with progression to T1D, and were included in RRR. A nutrient pattern corresponding to intake lower in linoleic acid, niacin, and riboflavin, and higher in total sugars, explained 18% of metabolite variability. Children scoring higher on this metabolite-related nutrient pattern at seroconversion had increased risk for progressing to T1D (HR = 3.17, 95%CI = 1.42-7.05). CONCLUSIONS: Combinations of nutrient intake reflecting candidate metabolites are associated with increased risk of T1D, and may help focus dietary prevention efforts.
OBJECTIVE: Our aim was to elucidate the role of diet in type 1 diabetes (T1D) by examining combinations of nutrient intake in the progression from islet autoimmunity (IA) to T1D. METHODS: We measured 2457 metabolites and dietary intake at the time of seroconversion in 132 IA-positive children in the prospective Diabetes Autoimmunity Study in the Young. IA was defined as the first of two consecutive visits positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). By December 2018, 40 children progressed to T1D. Intakes of 38 nutrients were estimated from semiquantitative food frequency questionnaires. We tested the association of each metabolite with progression to T1D using multivariable Cox regression. Nutrient patterns that best explained variation in candidate metabolites were identified using reduced rank regression (RRR), and their association with progression to T1D was tested using Cox regression adjusting for age at seroconversion and high-risk HLA genotype. RESULTS: In stepwise selection, 22 nutrients significantly predicted at least two of the 13 most significant metabolites associated with progression to T1D, and were included in RRR. A nutrient pattern corresponding to intake lower in linoleic acid, niacin, and riboflavin, and higher in total sugars, explained 18% of metabolite variability. Children scoring higher on this metabolite-related nutrient pattern at seroconversion had increased risk for progressing to T1D (HR = 3.17, 95%CI = 1.42-7.05). CONCLUSIONS: Combinations of nutrient intake reflecting candidate metabolites are associated with increased risk of T1D, and may help focus dietary prevention efforts.
Authors: Molly M Lamb; Brittni Frederiksen; Jennifer A Seifert; Miranda Kroehl; Marian Rewers; Jill M Norris Journal: Diabetologia Date: 2015-06-07 Impact factor: 10.122
Authors: Molly M Lamb; Melissa Miller; Jennifer A Seifert; Brittni Frederiksen; Miranda Kroehl; Marian Rewers; Jill M Norris Journal: Pediatr Diabetes Date: 2014-01-20 Impact factor: 4.866
Authors: Sari Niinistö; Hanna-Mari Takkinen; Iris Erlund; Suvi Ahonen; Jorma Toppari; Jorma Ilonen; Riitta Veijola; Mikael Knip; Outi Vaarala; Suvi M Virtanen Journal: Diabetologia Date: 2017-05-04 Impact factor: 10.122
Authors: M Simpson; H Brady; X Yin; J Seifert; K Barriga; M Hoffman; T Bugawan; A E Barón; R J Sokol; G Eisenbarth; H Erlich; M Rewers; J M Norris Journal: Diabetologia Date: 2011-08-20 Impact factor: 10.122
Authors: M M Lamb; X Yin; G O Zerbe; G J Klingensmith; D Dabelea; T E Fingerlin; M Rewers; J M Norris Journal: Diabetologia Date: 2009-06-23 Impact factor: 10.122
Authors: A Floegel; A von Ruesten; D Drogan; M B Schulze; C Prehn; J Adamski; T Pischon; H Boeing Journal: Eur J Clin Nutr Date: 2013-08-14 Impact factor: 4.016
Authors: Matej Oresic; Satu Simell; Marko Sysi-Aho; Kirsti Näntö-Salonen; Tuulikki Seppänen-Laakso; Vilhelmiina Parikka; Mikko Katajamaa; Anne Hekkala; Ismo Mattila; Päivi Keskinen; Laxman Yetukuri; Arja Reinikainen; Jyrki Lähde; Tapani Suortti; Jari Hakalax; Tuula Simell; Heikki Hyöty; Riitta Veijola; Jorma Ilonen; Riitta Lahesmaa; Mikael Knip; Olli Simell Journal: J Exp Med Date: 2008-12-15 Impact factor: 14.307
Authors: Randi K Johnson; Lauren A Vanderlinden; Fran Dong; Patrick M Carry; Jennifer Seifert; Kathleen Waugh; Hanan Shorrosh; Tasha Fingerlin; Brigitte I Frohnert; Ivana V Yang; Katerina Kechris; Marian Rewers; Jill M Norris Journal: Sci Rep Date: 2020-02-28 Impact factor: 4.379
Authors: Patrick M Carry; Lauren A Vanderlinden; Randi K Johnson; Teresa Buckner; Oliver Fiehn; Andrea K Steck; Katerina Kechris; Ivana Yang; Tasha E Fingerlin; Marian Rewers; Jill M Norris Journal: Diabetes Date: 2021-04-16 Impact factor: 9.337
Authors: Tim Vigers; Lauren A Vanderlinden; Randi K Johnson; Patrick M Carry; Ivana Yang; Brian C DeFelice; Alexander M Kaizer; Laura Pyle; Marian Rewers; Oliver Fiehn; Jill M Norris; Katerina Kechris Journal: Metabolites Date: 2021-08-14