Serum ferritin and glucose homeostasis: change in the association by glycaemic state

Data on the association between body iron and glucose homeostasis by the three glycaemic states are scarce. Thus, we investigated the association between body iron as assessed by a serum ferritin concentration and glucose homeostasis using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) and beta cell function (HOMA-BcF) in different glycaemic states.

A cross-sectional analysis was conducted in 2541 men aged 42-60 years in 1984-1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Subjects were classified into the three glycaemic states, normoglycaemia, prediabetes and type 2 diabetes (T2D), by fasting plasma glucose measurements and the information collected at study visit. The association between serum ferritin quartiles and HOMA-IR and HOMA-BcF for each glycaemic state was examined by analysis of covariance and linear regression analysis.

The mean age and serum ferritin concentrations were 53.1 years (standard deviation = 5.7, range = 42.0-61.3 years) and 166.2 µg/L (standard deviation = 141.7, range = 11-960 µg/L), respectively. After multivariable adjustments, a weak and direct association was observed between serum ferritin quartiles and HOMA-IR in normoglycaemia (P-trend = 0.001) but a direct association in prediabetes (P-trend = 0.007) and in T2D (P-trend = 0.078). In HOMA-BcF, the association was weak and direct in normoglycaemia (P-trend = 0.003), direct in prediabetes (P-trend = 0.005) and inverse in T2D (P-trend = 0.105). Strongest associations were observed in prediabetes (β = 0.25, 95% confidence interval = 0.14-0.36 and P = 0.004 in HOMA-IR; β = 0.23, 95% confidence interval = 0.15-0.31 and P = 0.008 in HOMA-BcF) after a 100-µg/L increase in serum ferritin (log-transformed).

These data suggest that both the strength and the direction of the association between body iron stores and glucose homeostasis are dependent on the glycaemic state of the population.