Abstract 15758: Diabetes is Associated With Higher Lymphocyte G-Protein Coupled Receptor Kinase-2 (grk2) Protein Levels in Patients With Left Ventricle Dysfunction Independently From Heart Failure Status
BACKGROUND: Diabetes mellitus (DM) is associated with impaired prognosis in patients (pts) with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated β-adrenergic receptor (βAR) activation by catecholamines causes G-protein coupled receptor kinase-2 (GRK2) up-regulation, which is responsible for βAR signaling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. In addition, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signaling. The aim of the present study was to compare lymphocyte GRK2 protein levels in pts with HF, with and without DM.
METHODS AND RESULTS: We studied 269 pts with systolic HF (left ventricular ejection fraction [LVEF] 30.63±7.64) with and without DM. No differences between the 2 groups were found for demography, HF etiology, LVEF, NYHA class, norepinephrine (NE) and NTproBNP. GRK2 was significantly higher in DM pts compared to non-DM. At multivariate logistic regression analysis, LVEF, NE, NTproBNP and diabetes independently predict GRK2 levels in the overall population.
Conclusion: DM is associated with significantly more elevated lymphocyte GRK2 protein levels in HF pts, reflecting more compromised cardiac sympathetic derangement, despite similar hemodynamic status and neuro-hormonal activation compared to HF pts without DM. These findings contribute to explain the negative prognostic impact of DM in pts with HF.
- © 2013 by American Heart Association, Inc.