To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.