显性和亚临床肝源性糖尿病及二甲双胍治疗对肝硬化腹水患者循环功能、肾功能、血流动力学、炎症活性及预后的影响。
Impact of overt and subclinical hepatogenous diabetes and metformin treatment on circulatory function, renal function and hemodynamics, inflammatory activity, and prognosis in patients with cirrhosis and ascites.
作者信息
Tsiakas Ilias, Kosmidou Maria, Despotis Grigorios, Biros Dimitrios, Tsiouris Spiridon, Xourgia Xanthi, Lakkas Lampros, Markopoulos Georgios S, Bairaktari Eleni, Kolios Georgios, Milionis Haralampos, Kalambokis Georgios
机构信息
First Division of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece (Ilias Tsiakas, Grigorios Despotis, Dimitrios Biros, Haralampos Milionis, Georgios Kalambokis).
Third Department of Internal Medicine, Papageorgiou Hospital, Thessaloniki, Greece (Maria Kosmidou).
出版信息
Ann Gastroenterol. 2025 Sep-Oct;38(5):545-553. doi: 10.20524/aog.2025.0990. Epub 2025 Aug 14.
BACKGROUND
Hepatogenous diabetes (HD) is common in advanced cirrhosis. The oral glucose tolerant test (OGTT) is frequently diagnostic, as fasting blood glucose (FBG) may be normal. We investigated the impact of FBG- and OGTT-diagnosed HD, and metformin treatment, on circulatory function, renal function and perfusion, and inflammatory activity in patients with cirrhosis and ascites. Also, long-term prognosis of HD under metformin/metformin-based treatment was assessed.
METHODS
Mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, glomerular filtration rate (GFR), renal blood flow (RBF), and plasma levels of lipopolysaccharide-binding protein (LBP), tumor-necrosis factor-α (TNF-α) and interleukin-6 were evaluated at baseline in patients with and without HD, and after 6 months of metformin treatment for newly diagnosed HD.
RESULTS
Compared to OGTT-HD (n=34) and no-HD (n=37), FBG-HD patients (n=35; newly-diagnosed, n=13) had significantly lower SVR (P=0.02/P=0.01), GFR (P=0.01/P=0.008) and RBF (P=0.02/P=0.01), and significantly higher CO (P=0.04/P=0.03), PRA (P=0.009/P=0.006), and levels of LBP (P=0.01/P=0.008) and TNF-α (P=0.03/P=0.02). Initiation of metformin in OGTT-HD and FBG-HD patients induced significant increases in SVR (P=0.02/P=0.04), GFR (P=0.02/P=0.04) and RBF (P=0.04/P=0.05), and significant decreases in PRA (P=0.02/P=0.03) and LBP (P=0.02/P=0.04). Three-year survival in OGTT-HD was significantly higher than in FBG-HD (75.3% vs. 55.3%; P=0.03) and similar to no-HD (81.7%).
CONCLUSIONS
Circulatory function and renal function and perfusion are aggravated by FBG-HD compared to OGTT-HD or no-HD, possibly because of greater inflammatory activity, while they improve significantly after metformin treatment. Early treatment of HD with metformin may improve prognosis.
背景
肝源性糖尿病（HD）在晚期肝硬化患者中很常见。口服葡萄糖耐量试验（OGTT）常用于诊断，因为空腹血糖（FBG）可能正常。我们研究了FBG诊断的HD和OGTT诊断的HD以及二甲双胍治疗对肝硬化腹水患者循环功能、肾功能及灌注和炎症活性的影响。此外，还评估了二甲双胍/基于二甲双胍治疗下HD的长期预后。
方法
在有或无HD的患者基线时，以及新诊断HD患者接受二甲双胍治疗6个月后，评估平均动脉压（MAP）、心输出量（CO）、体循环血管阻力（SVR，以MAP/CO比值表示）、血浆肾素活性（PRA）、血浆醛固酮、肾小球滤过率（GFR）、肾血流量（RBF）以及脂多糖结合蛋白（LBP）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6的血浆水平。
结果
与OGTT-HD患者（n = 34）和无HD患者（n = 37）相比，FBG-HD患者（n = 35；新诊断患者，n = 13）的SVR（P = 0.02/P = 0.01）、GFR（P = 0.01/P = 0.008）和RBF（P = 0.02/P = 0.01）显著降低，而CO（P = 0.04/P = 0.03）、PRA（P = 0.009/P = 0.006）以及LBP水平（P = 0.01/P = 0.008）和TNF-α水平（P = 0.03/P = 0.02）显著升高。OGTT-HD和FBG-HD患者开始使用二甲双胍后，SVR（P = 0.02/P = 0.04）、GFR（P = 0.02/P = 0.04）和RBF（P = 0.04/P = 0.05）显著升高，PRA（P = 0.02/P = 0.03）和LBP（P = 0.02/P = 0.04）显著降低。OGTT-HD患者的三年生存率显著高于FBG-HD患者（75.3%对55.3%；P = 0.03）且与无HD患者相似（81.7%）。
结论
与OGTT-HD或无HD相比，FBG-HD会加重循环功能、肾功能及灌注，可能是因为炎症活性更强，而二甲双胍治疗后这些情况会显著改善。早期使用二甲双胍治疗HD可能改善预后。
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