Abstract Body (Do not enter title and authors here): Introduction: Although diabetes mellitus (DM) and endothelial dysfunction are thought to affect atherogenic processes, we know little about the clinical impact of endothelial dysfunction on evolutional mechanisms of DM.
Hypothesis: This study assessed hypothesis that endothelial dysfunction accelerates diabetic evolution and adverse clinical events.
Methods: Endothelial dysfunction was graded by reactive changes in lumen diameter of right brachial artery following transient forearm occlusion (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with stable coronary artery disease using high-resolution ultrasonography.
The enrolled patients were categorized into 3 groups according to the values of FMD, and their glucose tolerance and adverse clinical events were followed-up for 36 months or more. We prospectively followed up diabetic evolution, which was defined as newly diagnosed DM by 75g-OGTT or new administration of an antidiabetic agent.
Results: For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD<4%; Group-L, n=174), more frequently manifested diabetic evolution [Group-L versus Group-M with mild endothelial dysfunction (4%≤FMD<8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, n=173): 25 (14.4%) versus 12 (7.0%) plus 7(4.0%), p<0.001, by Kaplan-Meier analysis].
The patients in Group-L more frequently resulted in fatal events [Group-L versus Group-M plus Group-H: 15(8.6%) versus 4(2.3%) plus 2(1.2%), p<0.001].
HbA1c significantly elevated in Group-L (5.9±0.6 to 6.2±0.9, p=0.009) but not in Group-M or in Group-H.
Cox proportional hazard model analysis including clinical variables showed that severe endothelial dysfunction was a significant predictor for future diabetic evolution (hazard ratio=2.69, p=0.011) and all-causal death (hazard ratio=5.87, p=0.009).
Conclusions: This is the first clinical ultrasonic vascular investigation demonstrating that endothelial dysfunction accelerates diabetic evolution and causes excess of fatal events and strategies based on practical status of endothelial dysfunction are required for metabolic and prognostic management.