Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.

Abstract

OBJECTIVE:

Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.

RESEARCH DESIGN AND METHODS:

The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population.

RESULTS:

Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 μg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-glutamyl transferase. Elevated TSAT (≥45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01).

CONCLUSIONS:

The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.

• Authors: Clara Podmore, Karina Meidtner, Matthias B Schulze, Robert A Scott, Anna Ramond, Adam S Butterworth, Emanuele Di Angelantonio, John Danesh, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Françoise Clavel-Chapelon, Amanda J Cross, Christina C Dahm, Guy Fagherazzi, Paul W Franks, Diana Gavrila, Sara Grioni, Marc J Gunter, Gaelle Gusto, Paula Jakszyn, Verena Katzke, Timothy J Key, Tilman Kühn, Amalia Mattiello, Peter M Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Emilio Sánchez-Cantalejo, Nadia Slimani, Ivonne Sluijs, Annemieke M W Spijkerman, Anne Tjonneland, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Edith J M Feskens, Nita G Forouhi, Stephen J Sharp, Elio Riboli, Claudia Langenberg, Nicholas J Wareham
• Journal: Diabetes care (Diabetes Care) Vol. 39 Issue 4 Pg. 572-81 (Apr 2016) ISSN: 1935-5548 [Electronic] United States
• PMID: 26861925 (Publication Type: Journal Article)
• Copyright: © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Biomarkers
• Transferrin
• C-Reactive Protein
• Ferritins
• Iron
• gamma-Glutamyltransferase
• Alanine Transaminase

Topics

• Adult
• Aged
• Aged, 80 and over
• Alanine Transaminase (blood)
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Diabetes Mellitus, Type 2 (blood, epidemiology)
• Female
• Ferritins (blood, metabolism)
• Follow-Up Studies
• Humans
• Incidence
• Iron (blood, metabolism)
• Male
• Middle Aged
• Multivariate Analysis
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Transferrin (metabolism)
• Young Adult
• gamma-Glutamyltransferase (blood)