Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2021; 12(11): 1856-1874
Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1856
Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review
Sofia Antoniou, Katerina K Naka, Marios Papadakis, Aris Bechlioulis, Agathocles Tsatsoulis, Lampros K Michalis, Stelios Tigas
Sofia Antoniou, Agathocles Tsatsoulis, Stelios Tigas, Department of Endocrinology, University of Ioannina, Ioannina 45110, Greece
Katerina K Naka, Aris Bechlioulis, Lampros K Michalis, 2nd Department of Cardiology and Michaelidion Cardiac Center, University of Ioannina, Ioannina 45110, Greece
Marios Papadakis, Department of Surgery II, University of Witten-Herdecke, Wuppertal 42283, Germany
Author contributions: Antoniou S and Papadakis M conceptualized the study and analyzed relevant studies for inclusion; Antoniou S, Naka KK and Tigas S designed the manuscript; Antoniou S, Papadakis M, Bechlioulis A, Tsatsoulis A and Michalis LK performed the literature search; Antoniou S drafted the manuscript; all authors reviewed and approved the final draft of the manuscript.
Conflict-of-interest statement: No conflict of Interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marios Papadakis, MD, MSc, PhD, Research Scientist, Surgeon, Department of Surgery II, University of Witten-Herdecke, Heusnerstrasse 40, Wuppertal 42283, Germany. marios_papadakis@yahoo.gr
Received: May 5, 2021
Peer-review started: May 5, 2021
First decision: July 15, 2021
Revised: July 29, 2021
Accepted: October 9, 2021
Article in press: October 9, 2021
Published online: November 15, 2021
Processing time: 193 Days and 20.5 Hours
Abstract

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.

Keywords: Glycemic control; Atherosclerosis; Type 2 diabetes mellitus; Cardiovascular disease; Carotid intima media thickness

Core Tip: Progression or even regression of atherosclerosis is possible in type 2 diabetes mellitus, especially at an early stage of the disease, with better glycemic control and use of newer agents, such as dipeptidyl peptidase 4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Despite considerable evidence, especially for structural markers like intima media thickness or coronary artery calcification, and pulse wave velocity, larger and longer trials are needed to establish their clinical utility and correlation with clinical end-points.