Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. May 20, 2015; 5(2): 110-119
Published online May 20, 2015. doi: 10.5493/wjem.v5.i2.110
Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus
Hiroyuki Konya, Masayuki Miuchi, Kahori Satani, Satoshi Matsutani, Yuzo Yano, Taku Tsunoda, Takashi Ikawa, Toshihiro Matsuo, Fumihiro Ochi, Yoshiki Kusunoki, Masaru Tokuda, Tomoyuki Katsuno, Tomoya Hamaguchi, Jun-ichiro Miyagawa, Mitsuyoshi Namba
Hiroyuki Konya, Satoshi Matsutani, Yuzo Yano, Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Hyogo 659-8502, Japan
Masayuki Miuchi, Kahori Satani, Taku Tsunoda, Takashi Ikawa, Toshihiro Matsuo, Fumihiro Ochi, Yoshiki Kusunoki, Masaru Tokuda, Jun-ichiro Miyagawa, Mitsuyoshi Namba, Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Tomoyuki Katsuno, Division of Innovative Diabetes Treatment, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Tomoya Hamaguchi, Center of Diabetes Therapy, Department of Internal Medicine, Itami City Hospital, Itami, Hyogo 664-8540, Japan
Author contributions: Konya H and Namba M were involved in collecting the required publications and editing the manuscript; Konya H wrote the manuscript; all authors organized the structure of the review.
Conflict-of-interest: We have no conflict of interest related to the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Hiroyuki Konya, MD, PhD, Department of Internal Medicine, Ashiya Municipal Hospital, 39-1, Asahigaoka-cho, Ashiya, Hyogo 659-8502, Japan.
Telephone: +81-797-312156 Fax: +81-797-228822
Received: October 4, 2014
Peer-review started: October 5, 2014
First decision: December 12, 2014
Revised: January 28, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 20, 2015

Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.

Keywords: Asymmetric dimethylarginine, Biomarker, Diabetes mellitus, Cardiovascular complications, Incretin

Core tip: Asymmetric dimethylarginine (ADMA) is an emerging independent biomarker for prospective cardiovascular (CV) complications. In our study, the results show that the cases with a high level of ADMA could have diabetes mellitus CV (DMCV) complications in the future within five years. Furthermore, not only ADMA but also urinary albumin was associated with DMCV complications in the multiple regression analyses. The clinical acceptation of this parameter will rely on the availability of therapies to immediately reduce ADMA such as incretin-based drugs, which could support the part of ADMA as an etiologic risk factor.