Journal article
Metabolomic signatures of dietary carbohydrates and differential association with type 2 diabetes
Nature Health, Vol.1(1), pp.145-157
01/2026
DOI: 10.1038/s44360-025-00023-8
Abstract
Metabolomic indices summarizing diet-related metabolic responses are instrumental for examining and replicating diet–disease associations. Here we aim to identify metabolomic signatures characterizing the amounts and types of dietary carbohydrate and assess their associations with type 2 diabetes (T2D) risk. Nutritional metabolomics indices were developed using data from 1,196 healthy participants in the Lifestyle Validation Study with 7-day diet records (7DDRs). Elastic net regression within cross-validation was used to derive metabolomic indices of total carbohydrates and primary food sources. Replication was conducted using feeding menu data among 153 women from the Nutrition and Physical Activity Assessment Study. Associations with incident T2D were examined using multivariable Cox regression in 11,454 participants from the Nurses’ Health Study, Nurses’ Health Study II and Health Professionals Follow-up Study. Metabolites positively associated with total carbohydrates and added sugars mainly included glycerolipids (diacylglycerols and triglycerides), whereas glycerophospholipids (phosphatidylethanolamines and phosphatidylcholines) were inversely associated. Whole grains were linked to betaine, 3-indolepropionic acid (IPA) and hippuric acid; vegetables and legumes to IPA,
N
-acetylornithine and pipecolic acid; and fruits to proline-betaine and IPA. Identified metabolomic signatures showed significant correlations with a 7-day diet record-assessed diet in the Lifestyle Validation Study (Pearson
r
0.33–0.65). In the Nutrition and Physical Activity Assessment Study, the metabolomic index of total carbohydrates was also significantly correlated with intake (
r
= 0.40). Signatures for total carbohydrates, added sugars, refined grains and potatoes were associated with higher T2D risk (HR per s.d. (95% confidence interval): 1.07 (1.02–1.12), 1.09 (1.03–1.14), 1.12 (1.07–1.18) and 1.36 (1.29–1.43)), whereas whole grain, vegetable, fruit and legume signatures were inversely associated (HR per s.d. (95% confidence interval): 0.73 (0.70–0.77), 0.95 (0.90–0.99), 0.88 (0.83–0.92) and 0.93 (0.88–0.97)). The metabolomic signatures of carbohydrate sources were differentially associated with T2D risk, highlighting the utility of blood metabolomics to objectively capture dietary carbohydrates and support dietary guidelines emphasizing fruits, vegetables and whole grains for diabetes prevention.
Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.
Details
- Title: Subtitle
- Metabolomic signatures of dietary carbohydrates and differential association with type 2 diabetes
- Creators
- Xiaowen Wang - Harvard UniversityPengfei Xia - Harvard UniversityFenglei Wang - Harvard UniversityZhiyuan Wu - Harvard UniversityYang Hu - Harvard UniversityA. Heather Eliassen - Harvard UniversityOana A. Zeleznik - Brigham and Women's HospitalShilpa N. Bhupathiraju - Harvard UniversitySeyed Mohammad Mousavi - Harvard UniversityRoss L. Prentice - Fred Hutch Cancer CenterLesley F. Tinker - Fred Hutch Cancer CenterCheng Zheng - University of Nebraska Medical CenterSimin Liu - University of California, IrvineYing Huang - Fred Hutch Cancer CenterSandi L. Navarro - Fred Hutch Cancer CenterMary C. Playdon - University of UtahSteven C. Moore - National Cancer InstituteLinda Snetselaar - University of IowaFred K. Tabung - The Ohio State UniversityJoAnn E. Manson - Brigham and Women's HospitalLihong Qi - University of California, DavisDaniel Raftery - University of WashingtonWalter C. Willett - Harvard UniversityJohanna W. Lampe - University of WashingtonMarian L. Neuhouser - Fred Hutch Cancer CenterQi Sun - Harvard University
- Resource Type
- Journal article
- Publication Details
- Nature Health, Vol.1(1), pp.145-157
- DOI
- 10.1038/s44360-025-00023-8
- ISSN
- 3005-0693
- eISSN
- 3005-0693
- Publisher
- Nature Publishing Group UK
- Number of pages
- 13
- Grant note
- NNF24SA0092022 / Novo Nordisk Fonden (Novo Nordisk Foundation) (https://doi.org/10.13039/501100009708) 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005 / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) (https://doi.org/10.13039/100000050) National Institutes of Health (grant No. UM1 CA186107, U01 CA176726, U01 CA167552, P01 CA87969, R01 HL034594, R01 HL035464, R01 HL60712, R01 DK120870, R01 DK126698, R01 DK119268, U2C DK129670, DK119268, R01 ES022981, R01 ES036206, R21 AG070375, P30 DK035816, P30 CA015704, R01 CA119171)
- Language
- English
- Date published
- 01/2026
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9985121598102771
Metrics
1 Record Views