title: Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study.
abstract: BACKGROUND
  Stable-isotope ratios of carbon (¹³C/¹²C, expressed as δ¹³C) and nitrogen (¹⁵N/¹⁴N, or δ¹⁵N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods.
  
  
  OBJECTIVE
  The objective was to investigate dietary correlates of δ¹³C and δ¹⁵N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study.
  
  
  METHODS
  Serum δ¹³C and δ¹⁵N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of δ¹³C and δ¹⁵N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression.
  
  
  RESULTS
  Mean (±SD) δ¹³C and δ¹⁵N were -22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and δ¹³C (r = 0.22) and δ¹⁵N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with δ¹³C but was significantly correlated with δ¹⁵N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ≤ 0.013). δ¹³C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas δ¹⁵N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001).
  
  
  CONCLUSIONS
  The isotope ratios δ¹³C and δ¹⁵N may both serve as potential biomarkers of fish protein intake, whereas only δ¹⁵N may reflect broader animal-source protein intake in a European population. The inverse association of δ¹³C but a positive association of δ¹⁵N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Pinal S
authors.initials: PS
authors.lastname: Patel
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Andrew J M
authors.initials: AJ
authors.lastname: Cooper
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Tamsin C
authors.initials: TC
authors.lastname: O'Connell
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Gunter G C
authors.initials: GG
authors.lastname: Kuhnle
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Kneale
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Angela M
authors.initials: AM
authors.lastname: Mulligan
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: From the MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom (PSP, AJMC, SB, NJW, and NGF); the Department of Archaeology & Anthropology, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO); the McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, United Kingdom (TCO and CKK); the University of Reading, Reading, United Kingdom (GGCK); and the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (AMM, RNL, K-TK, and GGCK).
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002247:Carbon Isotopes; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000378:metabolism; D004739:England / Q000453:epidemiology; D005260:Female; D029941:Fish Proteins / Q000008:administration & dosage* / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009587:Nitrogen Isotopes; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D002247:Carbon Isotopes; D004044:Dietary Proteins; D029941:Fish Proteins; D009587:Nitrogen Isotopes