Cardiac and plasma catecholamine responses to exercise in patients with type 2 diabetes: prognostic implications for cardiac-cerebrovascular events

BACKGROUND: Patients with diabetes mellitus have an altered exercise plasma catecholamine response, which may be related to the abnormal sympathoadrenal function and autonomic neuropathy. Presence of autonomic neuropathy is associated with poor prognosis, but relationship between exercise plasma catecholamine and prognosis has not been investigated. This study determined if altered plasma catecholamine response to exercise was associated with cardiac-cerebrovascular events. METHODS: Forty patients with type 2 diabetes without apparent macrovascular complications and 30 control subjects performed treadmill exercise with serial measurements of plasma norepinephrine and epinephrine. Clinical, exercise, and catecholaminergic variables considered relevant to the cardiac-cerebrovascular events were examined by Cox regression model. Analysis of 24-hour heart rate variability was performed in a subgroup of patients. RESULTS: During 7.2 years, 8 patients, but no control subjects, had events (3 myocardial and 5 cerebral infarctions). Compared with Event(-) patients, Event(+) patients had: (1) orthostatic hypotension; (2) lower peak exercise heart rate; (3) lower plasma norepinephrine immediately after exercise; and (4) lower plasma epinephrine at peak exercise. High frequency components in heart rate variability analysis were diminished in Event(+) patients. Multivariate analysis showed that peak heart rate (P = 0.04) and plasma epinephrine at peak exercise (P = 0.03) were independent predictors of subsequent events. CONCLUSIONS: These data suggest that chronotropic incompetence and lower plasma epinephrine response to exercise are associated with high risk of cardiac-cerebrovascular events in patients with type 2 diabetes.