Aims Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM.

Methods Middle‐aged normoglycaemic men (n = 895) participating in a prospective cohort study were followed up after 4 years.

Results At baseline proportions of serum esterified and non‐esterified saturated fatty acids were increased and polyunsaturated fatty acids decreased in men who after 4 years had developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid composition as recorded in 4‐day dietary records were noted. In logistic regression analyses adjusting for age; obesity; and fasting lipid, glucose and insulin concentrations, men with proportions of non‐esterified and esterified linoleate in the upper third had nearly half the risk for IFG or DM compared with the lower third. In covariate analyses, baseline non‐esterified linoleate proportions were associated with changes in fasting insulin and glucose concentrations over the 4‐year follow‐up. Baseline esterified fatty acid composition was also associated with changes in insulin.

Conclusions High serum linoleate proportions decreased the risk of developing IFG or DM in middle‐aged men over a 4‐year follow‐up, possibly mediated in part by insulin resistance. These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism.