Long- but not Short-Term Multifactorial Intervention Improves Endothelial Dysfunction in Patients with Diabetes Mellitus Type 2 and Coronary Artery Disease

Abstract

PURPOSE: We set out to assess the impact of 4 weeks in-hospital and further 5 months ambulatory multifactorial intervention program on changes of coronary risk factors and endothelial dysfunction of coronary arteries in patients with diabetes mellitus type 2 (DM) and coronary artery disease (CAD). METHODS: 24 patients with DM+CAD were randomized to either a multifactorial risk factor intervention program (I), which focused on high-intensity exercise training (6x15 min bicycle /day, 5 days / week) during a 4-week in-hospital phase, followed by 30 min ergometer / day, 5 days / week during a further 5 months home-based exercise phase, or a control group (C) in which usual care was rendered by patients' private physicians. Changes in diameter of coronary arteries in response to intracoronary infusion of increasing concentrations of acetylcholine (0.072, 0.72, 7.2 g/min) was assessed by quantitative coronary angiography and mean peak flow velocity by Doppler velocimetry. RESULTS: At baseline there were no significant differences between groups in the parameters studied (p=n.s.). After 4 weeks and 6 months there was significant improvement in I with regard to body weight, triglycerides, HbA1c, and maximal work capacity (all at least p < 0.05), whereas there were no differences observed in C (all p=n. s). Invasive measurements of endothelial function were not different at baseline and 4 weeks but showed significant improvement after 6 months in I (all at least p < 0.05) but not C. After 6 months but not after 4 weeks there was significant improvement in the diameter of epicardial coronary arteries and mean peak flow velocity both after acetylcholine or adenosine infusion in I (all p < 0,05), whereas in C values remained essentially unchanged. CONCLUSIONS:There was significant improvement in the risk factor profile of patients with DM+CAD after 4 weeks and 6 months. Although 4 weeks of intervention were too short to induce significant changes in endothelial function, beneficial changes became apparent at 6 months. The ability of the endothelium to restore its function only after prolonged intervention may be explained by the advanced disease progression which is typical for diabetics and responsible for patients' worse prognosis.