The Association Between Plasma Fatty Acid and Cognitive Function Mediated by Inflammation in Patients with Type 2 Diabetes Mellitus

Abstract

Purpose

To verify the mediating role of inflammatory factors in plasma fatty acid-induced changes in cognitive function in patients with type 2 diabetes mellitus (T2DM).

Patients and Methods

In this study, we evaluated the cognitive function of 372 Chinese patients (the average age was 58.00 (52.50, 63.00) years) with T2DM by using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), with plasma fatty acids measured by gas chromatography analysis and inflammatory cytokines determined by immune turbidimetric analysis and enzyme-linked immunosorbent assay (ELISA) to investigate whether there was a correlation between the plasma fatty acids, inflammatory cytokine levels and cognitive test scores in Chinese patients with T2DM.

Results

We found that the increase of waist circumference and hip circumference might lead to cognitive impairment and induce the inflammatory response. Higher saturated fatty acids (SFAs) levels in plasma were linked to cognitive decline, while higher monounsaturated fatty acids (MUFAs) intake might be a protective factor for cognitive function. In addition, higher levels of plasma n-6 polyunsaturated fatty acids (n-6 PUFAs) stood out as having association with lower cognitive function scores, while higher level of plasma C22:6 n-3 could be a predictor of better cognitive function. In our study, higher SFAs led to higher proinflammatory factor levels. Apart from that, MUFAs and stearoyl-CoA desaturase-18 (SCD-18) were positively related to hypersensitive C-reactive protein (hs-CRP). Meanwhile, higher level of plasma C20:0 could lead to better MMSE delayed recall by reduce the expression of hs-CRP.

Conclusion

Levels of plasma SFAs, C18:3 n-6, and C20:3 n-6 could be a predictor for worse cognitive function, while MUFAs and C22:6 n-3 could be a predictor for better cognitive function. The level of hs-CRP could be a mediator of C20:0 induced the change of cognitive function.

Keywords:

• cognitive function
• inflammatory cytokines
• plasma fatty acids
• T2DM
• the mediation model

Abbreviations

AD, Alzheimer’s disease; BMI, body mass index; D5D, delta-5-desaturase; D6D, delta-6-desaturase; ELISA, enzyme-linked immunosorbent assay; LCSFAs, long chain saturated fatty acids; HOMA-IR, homeostatic model assessment-IR; hs-CRP, hypersensitive C-reactive protein; IDF, International Diabetes Mellitus; IL, interleukin; ET, endotoxin; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; MUFAs, monounsaturated fatty acids; NF-κB, nuclear factor kappa B; OGTT, oral glucose tolerance test; PUFAs, polyunsaturated fatty acids; QUICKI, quantitative sensitivity check index; SCD, stearoyl-CoA desaturase; SFAs, saturated fatty acids; T2DM, type 2 diabetes mellitus; TLRs, toll-like receptors; TNFα, tumor necrosis factor-α.

Data Sharing Statement

The data that support the findings of this study are available on request from the corresponding author. The manuscript has been posted to the preprint server Research Square, the link was as follows ” DOI:10.21203/rs.3.rs-577863/v3”.

Ethics Statement

We confirm that the data accessed in this study complies with relevant data protection and privacy legislation.

Ethics Approval and Informed Consent

This research was approved by the Ethics Committee of the Beijing Friendship Hospital, Capital Medical University (Beijing, China) (2015-P2-090-02).

Acknowledgments

Thanks for all the participants in this study.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the Beijing Natural Science Foundation (NO. 7222242) and the National Natural Science Foundation of China (NO. 81472982).