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

Br J Nutr. 2014 Dec 14;112(11):1896-904. doi: 10.1017/S0007114514002852. Epub 2014 Oct 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / prevention & control
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / prevention & control
  • Diet, Mediterranean
  • Female
  • Ferritins / blood
  • Humans
  • Iron / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Transferrin / blood
  • Risk Factors
  • Spain


  • Receptors, Transferrin
  • Ferritins
  • Iron