Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes.

AIMS: To investigate the association between circulating non-transferrin-bound iron [NTBI], and markers of oxidative stress, endothelial function and inflammation in subjects with type 2 diabetes and non-diabetic subjects with varying degrees of obesity. METHODS: Plasma NTBI was measured by HPLC, together with total iron, iron-binding capacity, transferrin saturation and soluble transferrin receptor, together with total and reduced ascorbate, malondialdehyde [MDA], E-selectin and high-sensitivity c-reactive protein [hs-CRP] in groups of 28 subjects with type 2 diabetes, 28 non-obese controls and 17 obese non-diabetic subjects. RESULTS: Levels of NTBI were higher than controls in the diabetes group, but the total serum iron levels were lower. MDA levels were higher than controls in both the diabetes and obese groups, and this was associated with higher levels of oxidised ascorbate. hs-CRP levels were higher in both the diabetes and obese groups, and E-selectin was significantly higher in the diabetes group. There were strong positive correlations between HbA1c levels and NTBI [P<0.01], HbA1c and E-selectin [P<0.001] and NTBI and E-selectin [P<0.02] in the diabetes group. CONCLUSION: These results support the hypothesis that iron-mediated oxidative stress may be a mechanism linking poor glycaemic control with vascular dysfunction in type 2 diabetes.

On the source of the non-transferrin-bound iron which accumulates in packed red blood cell units during storage.

BACKGROUND: Recent studies have shown large increases in non-transferrin-bound iron (NTBI) and biomarkers of oxidative stress in the extracellular medium of packed red blood cell units during storage. It has been further suggested that transfusion-mediated iron and oxidative load may contribute to transfusion-related morbidity in premature babies. The origin and nature of the NTBI is currently unclear, but the release of iron from oxidatively modified haemoglobin and haem has been suggested. The purpose of this study was to investigate whether this may be the case. MATERIALS AND METHODS: The concentration of haem in the extracellular fluid of paediatric packed cell units stored from 3 to 35 days was measured using a commercial haem assay. In vitro studies were conducted using haem (haemin; ferriprotoporphyrin IX chloride) to determine whether the NTBI assay was able to react with and measure iron associated with haem in the presence and absence of oxidising agents. RESULTS: The level of haem in the extracellular fluid of paediatric packed cell units rose gradually from day 3 to day 21, then more rapidly to day 35. Very little NTBI was released from haem in the absence of oxidising agents, but the amount rose in a dose- and time-dependent manner in proportion to the oxidation of haem by incubation with H2O2. DISCUSSION: The results of the study imply that the NTBI measured in previous studies may derive from the oxidatively modified haem that builds up in the extracellular fluid of packed red blood cell units during storage. The potential influence of this on transfusion mediated morbidity is discussed.

Red meat, dietary heme iron, and risk of type 2 diabetes: the involvement of advanced lipoxidation endproducts.

There is growing evidence of disordered iron homeostasis in the diabetic condition, with links proposed between dietary iron intakes and both the risk of disease and the risk of complications of advanced disease. In the United States, Britain, and Canada, the largest dietary contributors of iron are cereals and cereal products and meat and meat products. This review discusses the findings of cohort studies and meta-analyses of heme iron and red meat intakes and the risk of type 2 diabetes. These suggest that processed red meat is associated with increased risk, with high intakes of red meat possibly also associated with a small increased risk. Historically, humans have relied on large quantities of heme iron and red meat in their diets, and therefore it is paradoxical that iron from meat sources should be associated with the risk of type 2 diabetes. A reason for this association may be drawn from studies of dietary advanced glycation and lipoxidation endproducts present in processed food and the mechanisms by which insulin output by pancreatic islet cells might be influenced by the protein modifications present in processed red meat.