Dysmetabolic iron overload and cardiometabolic diseases. Cause-effect relationship or indirect association?

The prevalence of cardiometabolic diseases is increasing all over the world. Insulin resistance has been proposed as one major factor of the Metabolic syndrome (MetS) that ultimately leads to type 2 Diabetes Mellitus (T2DM). The relationship between iron status and MetS has been scarcely described. This mini-review presents on one hand the existing knowledge on the effects of excess body iron (iron overload) on insulin resistance and on the other the link between hyperglycemia and alterations in iron metabolism. When the binding capacity of serum transferrin exceeds normal levels, free-iron induces the formation of reactive oxygen species (ROS) which may increase oxidative stress and cause tissue damage. In addition, ROS have been linked to insulin resistance, reduction in adiponectin release, and non-alcoholic fatty liver, among others. It is also discussed that as a consequence of glucose excess, transferrin, as other proteins, becomes glycated decreasing its iron binding capacity resulting in elevated free-iron levels and the consequent deleterious effects. As in both, T2DM and hemochromatosis patients, a significant high ferritin-dyslipemia relationship has been reported, present review hypothesizes that iron stored as “ferritin” partially escapes to plasma contributing to the vicious circle. Increases in liver free fatty acids availability and gluconeogenesis aggravate insulin resistance, giving rise to adyslipemic profile. Nonetheless, several points and action mechanisms are still poorly understood and require more studies to elucidate the role of iron in the etiology of cardiometabolic diseases. Finally, it is suggested that subjects predisposed to cardiometabolic diseases and/or to accumulate iron should limit the prolonged consumption of iron supplements or iron fortified foods. Strategies to decrease the bioavailability of iron in such vulnerable population groups, such as recommending high vegetable diets, deserve future investigation.Study partially granted by project AGL 2014-53207-C2-2R.Peer reviewe