Polyethylene Glycol Loxenatide Injection (GLP-1) Protects Vascular Endothelial Cell Function in Middle-Aged and Elderly Patients With Type 2 Diabetes by Regulating Gut Microbiota

Abstract

Objective: To evaluate the protective effect of Polyethylene Glycol Loxenatide Injection (Glucagon-like peptide-1, GLP-1) on endothelial cells from middle-aged and elderly patients with newly diagnosed or poorly controlled type 2 diabetes mellitus (T2DM). GLP-1 weekly formulation was analyzed for cardiovascular disease protection and correlated with intestinal flora.Design: Stool samples were collected from middle-aged and elderly patients with new-onset or poorly controlled type 2 diabetes in Longhu People’s Hospital and Shantou Central Hospital from June 2019 to November 2019. Samples were collected at week 0, 4, and 8 of treatment with GLP-1 weekly formulations. Samples were analyzed for metagenomic sequencing. Analysis was performed to compare the characteristics of the gut microbiota at week 0, 4, and 8 of GLP-1 treatment and to correlate different microbiota with characteristic clinical parameters.Results: Statistical differences were found in blood glucose lowering, cardiovascular endothelial, and inflammation-related indices between week 0 and W4 and in blood glucose lowering and cardiovascular endothelial indices from week 0 to 8 in the newly diagnosed or poorly controlled type 2 diabetic patients treated with GLP-1. Changes in gut microbiota at week 0, 4, and 8 after using GLP-1 were not statistically different, but had an overall trend of rising and then falling, and with different bacteria, that were correlated with different clinical indicators.Conclusion: GLP-1 improves endothelial cell function indicators in middle-aged and elderly diabetic patients, which may be related to its alteration of the population numbers of gut microbiota such as Acinetobacter, Eubacterium ramulus ATCC 29099, and Bacteroides_faecis. This study provides a guidance for the treatment of type 2 diabetic patients.

The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus—A Systematic Review

“…In particular, at the genus level, there was one significant difference at baseline, week 4, and week 8— Acinetobacter —and at the species level— Acinetobacter-unclassified . The improvement in vascular endothelial function (determined by the tissue factor, plasminogen activator inhibitor-1, Endothelin-1, von Willebrand factor, tissue type fibrinogen activator, Prostaglandin I2 (PGI2), and LDL-cholesterol) was positively associated with Bacteroides and Afebola and negatively correlated with Acinetobacter baumannii [ 38 ].…”

Role of gut microbiota in the pathogenesis and treatment of diabetes mullites: Advanced research-based review

“…GLP-1 will be increasingly released when GPR43 is activated, which enhances insulin secretion, suppresses glucagon production, and increases satiety ( Tolhurst et al, 2012 ). Of note, GLP-1 might also improve endothelial cell function by changing the composition of gut microbiota ( Chen et al, 2022 ). The GPR43 transgenic mouse showed improved metabolic parameters, such as reduced obesity, improved homeostasis, improved lean meat quality, and higher GLP-1 secretion ( Bjursell et al, 2011 ; Tolhurst et al, 2012 ; Kimura et al, 2013 ).…”

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review

“…Therefore, when the intestinal gram-negative bacteria change, it can affect the inflammatory state in the body. At the same time, some cytokines, such as IL-10 and IL-22, can play an anti-inflammatory role, while Enterobacter, Bacteroides fragilis, Achmania mucophilus, and Lactobacillus plantarum can induce the production of these cytokines ( Zhu et al., 2018 ; Chen et al., 2022 ). Secondly, GM can affect intestinal barrier function.…”