Excess body iron and the risk of type 2 diabetes mellitus: a nested case–control in the PREDIMED (PREvention with MEDiterranean Diet) study

Victoria Arija, José C Fernández-Cao, Josep Basora, Mònica Bulló, Nuria Aranda, Ramón Estruch, Miguel A Martínez-González, Jordi Salas-Salvadó

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6·0 (interquartile range 3·9-6·5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 μg/l in males and >139 μg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3·62, 95 % CI 1·32, 19·95; P= 0·022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3·02, 95 % CI 1·09, 8·39; P= 0·042), but no association with sTfR (OR 1·29, 95 % CI 0·51, 3·23; P= 0·722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and β-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.