Short-term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả: Tarik Delko, Michael Epstein, Adhideb Ghosh, Vasco Iten, Michael Kühne, Christian Meier, Alaa Othman, Caspar Joyce Peterson, Stéphanie Pfammatter, Isabel Reinisch, Eleonora Seelig, Patricia Arroyo Tardio, Susanne Thierry, Christian Wolfrum, Nicola Zamboni, Christine S Zuern

Ngôn ngữ: eng

Ký hiệu phân loại: 979.704 Statehood period, 1889-

Thông tin xuất bản: United States : Diabetes care , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 752844

 OBJECTIVE: Glucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms. RESEARCH DESIGN AND METHODS: This single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants. The trial was conducted at the University Hospital Basel, Basel, Switzerland. Participants received prednisone 30 mg/day in combination with metformin or placebo for two 7-day periods (1:1 randomization). The primary outcome, change in insulin sensitivity, was assessed using a two-sided paired t test. Before and after each study period, we conducted a mixed-meal tolerance test, blood metabolomics, and RNA sequencing of subcutaneous adipose tissue biopsy specimens. RESULTS: Metformin improved insulin sensitivity as assessed by the Matsuda index (n = 17
  mean change -2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin
  mean difference of change -4.94 [95% CI, -7.24, -2.65]
  P <
  0.002). Metabolomic and transcriptomic analyses revealed that metformin altered fatty acid flux in the blood and downregulated genes involved in fatty acid synthesis in adipose tissue. Metformin reduced markers of protein breakdown and bone resorption. Furthermore, metformin downregulated genes responsible for AMPK inhibition and affected glucagon-like peptide 1 and bile acid metabolism. CONCLUSIONS: Metformin prevents GC-induced insulin resistance and reduces markers of dyslipidemia, myopathy, and, possibly, bone resorption through AMPK-dependent and -independent pathways.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 36225755 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH