Insulin sensitivity and body composition in cirrhosis: changes after TIPS

Abstract

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7-7.3]. Fasting (f)-insulin increased from 123 +/- 81 to 193 +/- 124 pmol/l (P = 0.03), whereas f-glucose was unchanged (6.0 +/- 0.8 vs. 6.2 +/- 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7-22%) and 53% (CI: 14-90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 +/- 1.82 vs. 4.85 +/- 2.37 mg.kg(-1).min(-1)) and glucose tracer-based rate of disappearance were unchanged (5.01 +/- 1.61 vs. 4.97 +/- 2.13 mg.kg(-1).min(-1)). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 +/- 0.42 vs. 2.42 +/- 0.58 mg.kg(-1).min(-1)) and was suppressed equally by insulin (1.1 +/- 0.1 vs. 1.0 +/- 0.1 mg.kg(-1).min(-1)). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.