TY - JOUR
T1 - Association of multiple biomarkers of iron metabolism and type 2 diabetes
T2 - The EPIC-Inter act study
AU - Podmore, Clara
AU - Meidtner, Karina
AU - Schulze, Matthias B.
AU - Scott, Robert A.
AU - Ramond, Anna
AU - Butterworth, Adam S.
AU - Di Angelantonio, Emanuele
AU - Danesh, John
AU - Arriola, Larraitz
AU - Barricarte, Aurelio
AU - Boeing, Heiner
AU - Clavel-Chapelon, Françloise
AU - Cross, Amanda J.
AU - Dahm, Christina C.
AU - Fagherazzi, Guy
AU - Franks, Paul W.
AU - Gavrila, Diana
AU - Grioni, Sara
AU - Gunter, Marc J.
AU - Gusto, Gaelle
AU - Jakszyn, Paula
AU - Katzke, Verena
AU - Key, Timothy J.
AU - Kühn, Tilman
AU - Mattiello, Amalia
AU - Nilsson, Peter M.
AU - Olsen, Anja
AU - Overvad, Kim
AU - Palli, Domenico
AU - Quirós, J. Ramón
AU - Rolandsson, Olov
AU - Sacerdote, Carlotta
AU - Sánchez-Cantalejo, Emilio
AU - Slimani, Nadia
AU - Sluijs, Ivonne
AU - Spijkerman, Annemieke M.W.
AU - Tjonneland, Anne
AU - Tumino, Rosario
AU - Van Der A, Daphne L.
AU - Van Der Schouw, Yvonne T.
AU - Feskens, Edith J.M.
AU - Forouhi, Nita G.
AU - Sharp, Stephen J.
AU - Riboli, Elio
AU - Langenberg, Claudia
AU - Wareham, Nicholas J.
N1 - Funding Information:
Funding for the InterAct Project was provided by the EU FP6 Programme (grant LSHM-CT-2006-037197).
Publisher Copyright:
© 2016 by the American Diabetes Association.
PY - 2016/4
Y1 - 2016/4
N2 - 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 100μg/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.
AB - 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 100μg/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.
UR - http://www.scopus.com/inward/record.url?scp=84962074006&partnerID=8YFLogxK
U2 - 10.2337/dc15-0257
DO - 10.2337/dc15-0257
M3 - Article
C2 - 26861925
AN - SCOPUS:84962074006
SN - 0149-5992
VL - 39
SP - 572
EP - 581
JO - Diabetes Care
JF - Diabetes Care
IS - 4
ER -
