This study was undertaken in acute myocardial infarction (AMI) patients with noninsulin-dependent diabetes mellitus (type 2 DM) to investigate their impaired chronotropic response to exercise. Seventy-one AMI subjects entered the study, 30 with type 2 DM and 41 age-and body mass index-matched non-DM (control) patients. One month after the onset of AMI, these patients underwent cardiopulmonary exercise testing on a treadmill under a ramp protocol. Anaerobic threshold (AT) and peak oxygen uptake (peak VO2) were determined as indicators of exercise capacity. Plasma norepinephrine (NE) concentration was measured in blood samples obtained at 2 time points: during pre-exercise rest and immediately after peak exercise. The change in NE concentration during exercise, as an index of sympathetic nervous activity, was calculated as a percentage:∆ NE=[(NE during exercise)-(resting value)]/(resting value)× 100. The change in heart rate (HR) during exercise was calculated as a simple difference:∆ HR=[(peak HR)-(rest HR)]. Index of chronotropic response to exercise was then quantified as the∆ HR/∆ NE during exercise. No significant intergroup differences in ejection fraction at rest or HR at peak exercise were observed. However, VO2 at AT, peak VO2,∆ HR, and∆ HR/∆ NE were significantly lower in the type 2 DM group than in the non-DM group.∆ HR correlated with VO2 at AT (r= 0.49, P< 0.001) and with peak VO2 (r= 0.53, P< 0.001) in all subjects. Also,∆ HR/∆ NE correlated with VO2 at AT (r= 0.42, P< 0.001) and with peak VO2 (r= 0.44, P< 0.001) in all subjects. AMI patients with type 2 DM had impaired cardiopulmonary responses to maximal and submaximal exercise testing and impaired chronotropic response to exercise, even though their cardiac function at rest was similar to that of non-DM AMI patients. The data suggest that one mechanism of impaired cardiopulmo-