Experimental and epidemiological studies have reported positive associations between iron parameters and metabolic dysfunction including: Type 2 diabetes mellitus (T2DM) (1-6), metabolic syndrome (7-15), non-alcoholic fatty liver disease (NAFLD) (16-22) and insulin resistance (23,24) with a number of studies showing that reductions in total body iron via dietary modification (e.g., reducing red meat intake) or phlebotomy lead to increases in insulin sensitivity (25), decreases in insulin resistance (26), and reductions in the prevalence of complications associated with T2DM (5, 27), metabolic syndrome (28) and NAFLD (22, 29). Moreover, the risk associated with these outcomes and total body iron differ between males and females and it has been hypothesized that the divergence in risk of disease due to total body iron is related to the female reproductive lifespan (e.g., age at menarche, parity, oral contraceptive use and age at menopause). Regardless of study design, serum ferritin and transferrin saturation have consistently been used in these investigations to estimate total iron stores, which are affected by inflammation and demonstrate diurnal variation. using FeCOOK is recommended in order to replicate these findings among a larger sample comprised of both males and older females.
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