High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study

Abstract

Objective

Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population.

Methods

Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai’an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity.

Results

A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02–1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥35.25μg/mL) levels showed a 2.25-fold (95% CI 1.11–4.57; P = 0.024) increase compared to participants with low L-Val (<27.26 μg/mL) levels after adjusting for MDA and confounding factors.

Conclusion

High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.

Keywords:

• branched chain amino acids
• oxidative stress
• new diagnosed type 2 diabetes mellitus
• hydrophilic interaction chromatography-tandem mass spectrometric method

Data Sharing Statement

All data presented in the manuscript are available upon request.

Ethical Approval

Written informed consent was obtained from all participants who were informed in detail about the objectives and procedures of the study before. This cross-sectional study was rooted in Huaian Diabetes Prevention Program (HADPP) (ChiCTR-TRC-14005029) which was approved by the medical ethics committees of The Affiliated Huaian Hospital of Xuzhou Medical College. This study was conducted in accordance with the Declaration of Helsinki.

Consent

No consent was required for this 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; 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

The authors declare no conflicts of interest.

Additional information

Funding

The work was supported by the National Natural Sciences Foundation of China to Wen Hu (No.81700776), the Health Department Fund Projects of Jiangsu Province to WenHu (No.H2018054) and Major Research plan of the National Natural Science Foundation of China to Hongwen Zhou [grant number 91854122].