Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study

Am J Clin Nutr. 2014 Aug;100(2):708-18. doi: 10.3945/ajcn.113.068577. Epub 2014 Jul 2.

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.

Design: 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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Carbon Isotopes
  • Case-Control Studies
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet / adverse effects*
  • Dietary Proteins / administration & dosage*
  • Dietary Proteins / metabolism
  • England / epidemiology
  • Female
  • Fish Proteins / administration & dosage*
  • Fish Proteins / metabolism
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Nitrogen Isotopes
  • Risk Factors
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Carbon Isotopes
  • Dietary Proteins
  • Fish Proteins
  • Nitrogen Isotopes