Iron metabolism is prospectively associated with insulin resistance and glucose intolerance over a 7-year follow-up period: the CODAM study

Objectives: Several markers of iron metabolism have been associated with insulin resistance (IR) and type 2 diabetes mellitus in cross-sectional studies. However, prospective data on these associations are scarce, and it is currently unclear in which tissues iron metabolism may contribute to IR. Therefore, we investigated whether markers of iron metabolism were associated with IR in muscle, liver, and adipocytes, and with glucose intolerance over a 7-year follow-up period. Design and methods: Serum ferritin, transferrin, total iron, non-transferrin-bound iron, and transferrin saturation were determined at baseline of a prospective cohort study in 509 individuals (60 % men, age 59 ± 6.9 years, body mass index 28.5 ± 4.3). Both at baseline and after a 7-year follow-up (n = 386), measures of glucose, insulin (during glucose tolerance tests), and non-esterified fatty acids were obtained. Using generalized estimating equations, we investigated associations between baseline iron markers and indices of muscle, liver, and adipocyte insulin resistance (adipocyte IR), as well as glucose intolerance, over the 7-year period. Results: Over a 7-year period, baseline serum ferritin (per 10 μg/L increase) was positively associated with homeostasis model assessment insulin resistance (HOMA2-IR) [β = 0.77 % (95 % CI 0.50-1.03)], hepatic insulin resistance (hepatic IR) [β = 0.39 % (0.23-0.55)] , adipocyte IR [β = 1.00 % (0.65-1.35)], and AUC glucose [β = 0.32 % (0.18-0.46)] after adjustment for several covariates, including inflammatory markers (all p \u3c 0.001). Similarly, serum transferrin (per 0.1 g/L) was associated with HOMA2-IR [β = 2.66 % (1.55-3.78)], hepatic IR [β = 1.16 % (0.47-1.85)] , adipocyte IR [β = 3.75 % (2.27-5.25)], and AUC glucose [β = 1.35 % (0.74-1.96)] over 7 years. Conclusions: Iron metabolism and related factors may contribute to IR in muscle, liver, and adipocytes, eventually leading to impaired glucose metabolism and hyperglycaemia