Clinical efficacy and metabolomics study of Wendan Decoction in the treatment of phlegm-dampness obstructive sleep apnea-hypopnea syndrome with type 2 diabetes mellitus

Abstract

Ethnopharmacological relevance: Wendan Decoction (WDD) is one of the classic traditional Chinese prescriptions that has been used in the treatment of type 2 diabetes mellitus (T2DM), metabolic syndrome, obstructive sleep apnea-hypopnea syndrome (OSAHS) and so on. The therapeutic effects and mechanism of WDD remain to be explored, especially from the perspective of metabolomics, oxidative stress and inflammation.

Aim of the study: To investigate the therapeutic and metabolic regulatory effects and the underlying mechanism of WDD in OSAHS with T2DM patients.

Materials and methods: All included patients were from Rudong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu Province, China. Both groups received lifestyle interventions; at the same time, all of them were administered metformin (1500 mg/day) and dapagliflozin (10 mg/day), and the treatment group was administered WDD orally. All patients were treated for two months. Before and after treatment, the changes in clinical symptoms and signs of the two groups of patients were evaluated, and the detection indicators such as body mass index (BMI), apnea-hypopnea index (AHI), lowest arterial oxygen saturation (LSaO₂), Epworth sleepiness scale (ESS), percentage of total sleep time with oxygen saturation <90% (TST90), fasting plasma glucose (FPG), 2-h post-load glucose(2h-PG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)，hemoglobin A1c (HbA1c), blood lipid levels, as well as the adverse reactions and compliance of the patients were observed and detection of serum metabolites in patients to screen out specific biomarkers. The serum metabolic profile of WDD in OSAHS with T2DM patients was explored using ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q Orbitrap HRMS).

Results: After treatment with WDD for 8 weeks, biochemical indicators, including BMI, FPG, 2h-PG, blood lipid, FINS, HbA1c, AHI, ESS, LSaO₂, TST90, and HOMA-IR, were significantly improved. Serum metabolomic analysis showed that metabolites were differentially expressed before and after WDD-treated patients. Metabolomics results revealed that WDD regulated the biomarkers, such as DL-arginine, guaiacol sulfate, azelaic acid, phloroglucinol, uracil, L-tyrosine, cascarillin, Cortisol and L-alpha-lysophosphatidylcholine. Pathway enrichment analysis showed that the metabolites were associated with oxidative stress and inflammation.

Conclusion: The study based on clinical research and metabolomics indicated that WDD can improve OSAHS with T2DM through multiple targets and pathways, and it may be a useful alternative therapy for the treatment of OSAHS with T2DM patients.

Keywords: Metabolomics; OSAHS; Phlegm-dampness; Type 2 diabetes mellitus; Wendan Decoction.