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Protective effect of intranasal insulin on postoperative cognitive dysfunction in elderly patients with metabolic syndrome undergoing noncardiac surgery: a randomized clinical trial

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Abstract

Background

Insulin plays a crucial and multifactorial role in cognitive activity, with insulin resistance appearing in neurodegenerative and metabolic diseases. Insulin resistance contributes to the pathobiology of postoperative cognitive dysfunction (POCD) in experimental models, which can be rescued by intranasal insulin administration.

Aims

To test the effect of intranasal insulin on the incidence of POCD in elderly patients with metabolic syndrome.

Methods

The study was designed as a randomized, double-blind, placebo-controlled clinical trial. 116 elderly participants were randomly assigned to receive either 40 IU insulin (n = 58) or placebo (n = 58) for 7 days. The primary outcome was the incidence of POCD at 7 days and 3 months after surgery. Secondary outcomes included the degree of peripheral insulin resistance postoperatively, changes in peripheral inflammation levels and the safety of interventions.

Results

The results showed that POCD occurred in the insulin group on the 7th postoperative day in 11 (20.8%) patients, which was fewer than the 23 (45.1%) patients in the placebo group (P = 0.008). The insulin group indicated better cognitive functional performance on language and memory test than the placebo group (P < 0.05). Mean peripheral plasma concentration of TNF-α (P < 0.05) and CRP (P < 0.001) in the insulin group was significantly declined compared with the placebo group on D3 and D7.

Conclusions

Intranasal insulin administration reduced the incidence of POCD and alleviated peripheral inflammatory levels in elderly patients with metabolic syndrome.

Trial registry

Chinese Clinical Trial Registry (ChiCTR1800015502).

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Data availability

The originale contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.

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Acknowledgements

Assistance with the article: we thank all included patients, all physicians, paramedics and nurses from the participating hospitals, who supported the protocol development, implementation and compliance adherence of this clinical trial. We thank all departments of the Third Xiangya Hospital of Central South University involved in the project: Departments of General Surgery, Thoracic Surgery, Urological Surgery, Orthopedic Surgery and Central Lab.

Funding

The trial was funded by the National Natural Science Foundation of China 81901842, China Primary Health Care Foundation YLGX-WS-2020003 and Natural Science Foundation of Hunan Province 2021JJ40936.

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Authors and Affiliations

  1. Department of Anesthesia, The Third Xiangya Hospital of Central South University, Changsha, China

    Yang Mi, Ouyang Wen, Long Ge, Liu Xing, Tong Jianbin, Tang Yongzhong & He Xi

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  1. Yang Mi
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  2. Ouyang Wen
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  3. Long Ge
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  4. Liu Xing
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  5. Tong Jianbin
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  6. Tang Yongzhong
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  7. He Xi
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Contributions

HX, YM, LG and OW: designed the study. Material preparation and data collection were performed by LG and TY. LX and TJ: was responsible for the statistical design of the study and for carrying out the statistical analysis. The first draft of the manuscript was written by YM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to He Xi.

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Conflict of interest

All the authors declare that there is no conflict of interest.

Ethical approval

Ethical approval for this study (ethical code: K18193) was provided by the Ethical Committee of the Third Xiangya Hospital of Central South University.

Informed consent

Informed consent was obtained from all subjects involved in the study.

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Mi, Y., Wen, O., Ge, L. et al. Protective effect of intranasal insulin on postoperative cognitive dysfunction in elderly patients with metabolic syndrome undergoing noncardiac surgery: a randomized clinical trial. Aging Clin Exp Res 35, 3167–3178 (2023). https://doi.org/10.1007/s40520-023-02593-7

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  • DOI: https://doi.org/10.1007/s40520-023-02593-7

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