Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2024; 15(6): 1263-1271
Published online Jun 15, 2024. doi: 10.4239/wjd.v15.i6.1263
Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes
Xiang-Yu Gao, Chen-Xia Zhou, Hong-Mei Li, Min Cheng, Da Chen, Zi-Yi Li, Bo Feng, Jun Song
Xiang-Yu Gao, Chen-Xia Zhou, Hong-Mei Li, Da Chen, Zi-Yi Li, Bo Feng, Jun Song, Department of Endocrinology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Xiang-Yu Gao, Department of Endocrinology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266000, Shandong Province, China
Min Cheng, Department of Immunization Program, Huangdao District Center for Disease Prevention and Control, Qingdao 266400, Shandong Province, China
Co-first authors: Xiang-Yu Gao and Chen-Xia Zhou.
Co-corresponding authors: Jun Song and Bo Feng.
Author contributions: Song J and Feng B designed the study and provided critical suggestions of the manuscript and should be considered as co-corresponding authors; Gao XY and Zhou CX analyzed the data, illustrated the results, and wrote the initial manuscript, these authors contributed equally to this work; Li HM and Cheng M participated in samples collection and information input; Chen D and Li ZY corrected language errors and revised the article critically for important intellectual content.
Supported by the Academic Leaders Training Program of Pudong Health Bureau of Shanghai, No. PWRd2023-03; Clinical Research Fund of Shanghai Municipal Commission of Health, No. 202040136; National Natural Science Foundation of China, No. 82070842; and Jiangxi Health Commission Science and Technology Plan Project, No. 202212838 and No. 202212852.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Shanghai East Hospital (Approval No. 2021023).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: All datasets generated for this study were all included in the manuscript files and the raw data may be obtained from the corresponding author for appropriate justification.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Song, PhD, Department of Endocrinology, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. songjuntj@tongji.edu.cn
Received: December 22, 2023
Revised: March 28, 2024
Accepted: April 24, 2024
Published online: June 15, 2024
Abstract
BACKGROUND

Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM).

AIM

To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels.

METHODS

A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.

RESULTS

The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-β was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control.

CONCLUSION

The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

Keywords: Type 2 diabetes mellitus, Hemoglobin A1c, Proton magnetic resonance spectroscopy, Neurotransmitters, Central neuropathy

Core Tip: Diabetic neuropathy is one of the most common chronic complications, and its pathogenesis has not been fully clarified until now, especially the central neuropathy. Cognitive dysfunction is the main manifestation of central neuropathy, although cognitive impairments tend to be neglected in diabetes, there is factually increasing evidence linking diabetes mellitus (DM) to cognitive dysfunction. Several studies indicated that the changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities. Here, we described the relationship between cerebral neurotransmitters concentrations that were measured using proton magnetic resonance spectroscopy and hemoglobin A1c levels in patients with type 2 DM.