William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Adult Critical Care Unit, Royal London Hospital, London, UK.
JPEN J Parenter Enteral Nutr. 2023 May;47(4):459-475. doi: 10.1002/jpen.2481. Epub 2023 Feb 22.
Skeletal muscle wasting is a determinant of physical disability in survivors of critical illness. Intramuscular bioenergetic failure, altered substrate metabolim, and inflammation are likely underpinning mechanisms. We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, on muscle-related outcomes in adults.
We included randomized controlled trials in which pioglitazone was administered (no dose/dosage restrictions) and muscle-related outcomes were reported. We searched MEDLINE, CENTRAL, EMBASE, CINAHL, and trial registries. Risk of bias was assessed using RoB 2. Primary outcomes were physical function and symptoms, muscle mass and function, or body composition and muscular compositional change. Secondary outcomes included muscle insulin sensitivity, mitochondrial effects, and intramuscular inflammation.
Fourteen studies over 19 publications (n = 474 patients) were included. Lean body mass was unaffected in three studies (n = 126) and increased by 1.8-1.92 kg in two studies (P = 0.02 and 0.003, respectively; n = 48). Pioglitazone was associated with increased peripheral insulin sensitivity (+23%-72%, standardized mean difference of 0.97 from trial start point to end point [95% CI, 0.36-1.58; n = 213]). Treatment reduced intramuscular tumor necrosis factor-α (TNF-α) levels (-30%; P = 0.02; n = 29), with mixed effects on serum TNF-α and intramyocellular lipid concentrations. Treatment increased intramuscular markers of adenosine triphosphate (ATP) biosynthesis (ATP5A [+33%, P ≤ 0.05], ETFA [+60%, P ≤ 0.05], and CX6B1 [+ 33%, P = 0.01] [n = 24]), PGC1α and PGC1β messenger RNA expression (P < 0.05; n = 26), and AMPK phosphorylation (+38%, P < 0.05; n = 26). These data have low-quality evidence profiles owing to risk of bias.
Pioglitazone therapy increases skeletal muscle insulin sensitivity and can decrease intramuscular inflammation.
骨骼肌减少是危重病幸存者身体残疾的决定因素。肌肉内的生物能量衰竭、代谢底物改变和炎症可能是潜在的机制。我们研究了过氧化物酶体增殖物激活受体 γ 激动剂吡格列酮对成人肌肉相关结局的影响。
我们纳入了吡格列酮给药（无剂量/剂量限制）且报告肌肉相关结局的随机对照试验。我们检索了 MEDLINE、CENTRAL、EMBASE、CINAHL 和试验注册处。使用 RoB 2 评估偏倚风险。主要结局是身体功能和症状、肌肉质量和功能或身体成分和肌肉组成变化。次要结局包括肌肉胰岛素敏感性、线粒体效应和肌肉内炎症。
纳入了 19 篇出版物中的 14 项研究（n=474 名患者）。在三项研究中（n=126），瘦体重没有变化，在两项研究中（P=0.02 和 0.003，分别；n=48）增加了 1.8-1.92kg。吡格列酮与外周胰岛素敏感性增加有关（+23%-72%，试验起点到终点的标准化均数差为 0.97[95%CI，0.36-1.58；n=213]）。治疗降低了肌肉内肿瘤坏死因子-α（TNF-α）水平（-30%；P=0.02；n=29），对血清 TNF-α 和肌内脂质浓度的影响不一。治疗增加了肌肉内三磷酸腺苷（ATP）合成的标志物（ATP5A[+33%，P≤0.05]、ETFA[+60%，P≤0.05]和 CX6B1[+33%，P=0.01]）[n=24]、PGC1α 和 PGC1β信使 RNA 表达（P<0.05；n=26）和 AMPK 磷酸化（+38%，P<0.05；n=26）。由于偏倚风险，这些数据的证据质量等级较低。
吡格列酮治疗可增加骨骼肌胰岛素敏感性，并可减少肌肉内炎症。
