Comparison of Efficacy and Safety of Cilostazol/Extract of Ginkgo biloba vs. Aspirin in Carotid Atherosclerosis in Patients with Diabetes Mellitus (Diabetes Metab J 2026;50:357-67)
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We would like to thank Saleh et al. for their interest in our recent article, “Comparison of efficacy and safety of cilostazol/extract of Ginkgo biloba vs. aspirin in carotid atherosclerosis in patients with diabetes mellitus” [1]. We appreciate their comments on methodological aspects of carotid intima-media thickness (cIMT) measurement and are pleased to have the opportunity to provide further clarification.
In our study, cIMT and plaque assessments were conducted using Philips vascular plaque quantification software (QLAB–VPQ plug-in, Philips Medical Systems, Andover, MA, USA). This validated software enables semi-automated detection of vessel walls and lumen borders from three-dimensional sweep recordings, with manual adjustments applied when necessary. Plaque areas were analyzed sequentially and summed to determine total plaque burden. The procedure was applied consistently throughout the study. Our reference to Polak et al. [2] was intended to provide context regarding the reproducibility of cIMT measurements and the comparison between manual and edge-detection techniques, rather than imply that their exact algorithm was used.
All baseline and follow-up scans were performed at identical carotid artery segments (common carotid artery, bulb, and internal carotid artery) using anatomical landmarks and standardized scanning protocols. Each measurement was repeated three times, and intra- and interobserver reliability was excellent (intraclass correlation coefficient, 0.969), supporting the robustness of our findings. In addition, cIMT measurements were taken at the end-diastolic phase according to Mannheim consensus recommendations, which are widely validated and remain the standard for cIMT assessment. This approach minimizes variability due to arterial wall motion and ensures consistency across repeated measurements.
Finally, cIMT is a simple and widely used measure of carotid atherosclerosis but may not fully represent the complexity of plaque morphology [3]. Specific plaque characteristics, including lipid-rich necrotic core, disseminated calcification, intraplaque hemorrhage, and thin fibrous cap, are strongly associated with plaque vulnerability and cardiovascular risk [4]. However, B-mode ultrasonography has a limited ability to accurately identify these compositional features.
We acknowledge that cIMT is a surrogate marker with inherent limitations. Its submillimeter scale makes it highly sensitive to technical factors, which should be considered when interpreting results. Nonetheless, our randomized design, blind assessment, and consistent methodology across groups help reduce potential bias. Notably, the cilostazol (CTZ)/extract of Ginkgo biloba (EGb) group demonstrated a statistically significant reduction in bulb cIMT compared with aspirin. In addition, this group showed significant increases in high-density lipoprotein cholesterol and decreases in triglycerides, as well as reductions in aspartate aminotransferase and alanine aminotransferase levels, which are well established markers for metabolic risk [5]. These findings are consistent with previous studies and suggest that CTZ and EGb may improve lipid metabolism, endothelial function, and vascular health.
In summary, we would like to thank Saleh et al. for their constructive comments. We hope that these clarifications address the concerns raised and reaffirm that our study provides supportive evidence for CTZ/EGb as a potential strategy to attenuate atherosclerosis in patients with type 2 diabetes mellitus. We agree that larger-scale and longer-term studies are warranted to confirm these findings.
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CONFLICTS OF INTEREST
Sang Yong Kim has been an associate editor of the Diabetes & Metabolism Journal since 2022. He was not involved in the review process of this article. Otherwise, there was no conflict of interest.