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

Ilias Tsiakas; Maria Kosmidou; Grigorios Despotis; Dimitrios Biros; Spiridon Tsiouris; Xanthi Xourgia; Lampros Lakkas; Georgios S. Markopoulos; Eleni Bairaktari; Georgios Kolios; Haralampos Milionis; George Kalambokis

Authors Ilias Tsiakas, Maria Kosmidou, Grigorios Despotis, Dimitrios Biros, Spiridon Tsiouris, Xanthi Xourgia, Lampros Lakkas, Georgios S. Markopoulos, Eleni Bairaktari, Georgios Kolios, Haralampos Milionis, George Kalambokis.

Abstract

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; newlydiagnosed, 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 OGTTHD 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.

Keywords Hepatogenous diabetes, oral glucose tolerant test, metformin, systemic inflammation, circulatory function

Ann Gastroenterol 2025; 38 (5): 545-553