Increased Serum Trimethylamine N-Oxide Level in Type 2 Diabetic Patients with Mild Cognitive Impairment

Abstract

Purpose

Trimethylamine N-oxide (TMAO) is a metabolite of phosphatidylcholine in red meat and other diets, which is associated with cardiovascular and other diseases. The aim of this study is to evaluate the associations of serum TMAO with mild cognitive impairment (MCI) in the Chinese type 2 diabetes mellitus (T2DM) population.

Materials and Methods

A total of 253 hospitalized T2DM patients and 150 healthy controls were included in this cross-sectional study. Montreal Cognitive Assessment (MoCA) assessed the cognition function, and the 253 T2DM patients were divided into 74 subjects with MCI and 179 with non-MCI. Demographic data and biochemical test results were evaluated. Serum TMAO level was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Results

A higher serum TMAO level was observed in T2DM patients compared with the healthy controls (P < 0.001). Among all T2DM patients, the MCI group (n = 74) showed higher serum TMAO levels than the non-MCI group. Spearman correlation test showed that TMAO levels were significantly positively correlated with age (r = 0.147, P = 0.019), body mass index (BMI) (r = 0.153, P = 0.015), diabetes duration (r = 0.160, P = 0.011), HbA1c (r = 0.138, P = 0.029), triglyceride (TG) (r = 0.138, P = 0.029), creatinine (r = 0.184, p = 0.003), hs-CRP (r = 0.243, P < 0.001), and were negatively correlated with HDL-C (r = −0.144, P = 0.022), BDNF (r = −0.165, p = 0.009), and MoCA (r = −0.386, P < 0.001) score (all P < 0.05). Multivariable Logistic regression identified high serum TMAO level as a significant independent factor of MCI in the T2DM patients (OR = 1.404, 95% CI = 1.255–1.571; P < 0.001).

Conclusion

Our study showed that T2DM patients with MCI have elevated serum TMAO levels.

Keywords:

• trimethylamine N-oxide
• type 2 diabetes mellitus
• mild cognitive impairment
• Montreal Cognitive Assessment
• healthy control

Ethics Statement

All methods and procedures used in this study were in agreement with the ethical principles and standards of the institutional and national bioethical commission and with the Helsinki Declaration of 1964 and its later revisions. The Ethics Committee of Shanghai University of Medicine and Health Science Affiliated Zhoupu Hospital approved this study. All subjects provided informed consent to participate in the study.

Acknowledgment

We sincerely thank all of the participants in our study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; they took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors in this article declared that they do not have any conflict of interest.

Additional information

Funding

The work was supported by The work was supported by 1) Health plan scientific research project of Shanghai Pudong New Area Health Committee (pw2020A-63); 2)The Outstanding Clinical Discipline Project of Shanghai Pudong (Grant No. : PWYgy2021-02).