β-Adrenergic Responsiveness in the Type 2 Diabetic Heart: Effects on Cardiac Reserve

Abstract

Type 2 diabetes (T2D) is associated with reduced cardiac reserve and aerobic capacity. Altered myocardial autonomic nervous regulation has been demonstrated in humans with diabetes (indirectly) and animal models (directly). Purpose This study aimed to determine the chronotopic and inotropic response of the type 2 diabetic heart to β-adrenergic stimulation. Methods Eight people with uncomplicated T2D and seven matched controls performed a dual-energy x-ray absorptiometry scan and VO 2peak test. Plasma catecholamines were determined at rest and during peak exercise. On a second visit, HR and left ventricular contractility were assessed using echocardiography during supine rest, parasympathetic blockade (atropine), and during incremental β-adrenergic stimulation (dobutamine). Results VO 2peak and HR reserve were lower in T2D (P < 0.05) as expected. Both groups increased norepinephrine comparably (P = 0.23) during peak exercise; however, epinephrine increased less in the T2D group (P < 0.05). The dobutamine dose required to achieve 85% of age-predicted maximal HR was 36% higher in CON (P < 0.05). Resting HR was higher (P < 0.01) and stroke volume indexed to fat free mass was smaller (P < 0.05) in T2D. During dobutamine infusion the response (% change) in HR, end-diastolic volume FFM, stroke volume, ejection fraction, and cardiac output were not different between the groups. However, HR was higher (P < 0.01) and end-diastolic volume indexed to fat free mass (P < 0.01), stroke volume FFM (P < 0.01), ejection fraction (P < 0.05), and stroke work (P < 0.01) were lower in T2D. Conclusions Although the type 2 diabetic heart worked at smaller volumes, the HR and contractile response to β-adrenergic stimulation were unaffected by diabetes. The reduced cardiac reserve observed in uncomplicated T2D was not explained by impaired myocardial sympathetic responsiveness but may reflect changes in the loading conditions or function of the diabetic left ventricle.