European Heart Journal Advance Access published online on November 12, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp482
Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus
1 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 650 Charles E. Young Drive South, B2-085J CHS, Box 95648, Los Angeles, CA 90095-6948, USA
2 Département de Médicine Interne, Service Cardiologie, Hôpitaux Universitaires de Genève (HUG), Genève, Switzerland
3 Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
4 Institute for Medical Statistics and Biometry, Albert Ludwig University, Freiburg, Germany
Received 14 July 2009; revised 10 September 2009; accepted 1 October 2009 * Corresponding author. Tel: +1 310 825 3076, Fax: +1 310 267 2677, Email: hschelbert{at}mednet.ucla.edu
Aims: To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU).
Methods and results: In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima–media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P 
0.036 and r = 0.46, P 0.055) and with an improvement in endothelium-related 
MBF to CPT and to adenosine (r = 0.46, P 0.038 and r = 0.36, P 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in MBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P 0.001 by one-way analysis of variance).
Conclusion: In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.
Key Words: Cardiovascular disease prevention • Carotid IMT • Coronary artery calcification • Coronary circulation • Endothelium • Diabetes mellitus • Positron emission tomography