Insulin sensitivity and body composition in cirrhosis: changes after TIPS

Area of Science:

• Endocrinology
• Gastroenterology
• Metabolic Research

Background:

• Transjugular intrahepatic porto-systemic shunt (TIPS) is known to increase body cell mass (BCM) in liver cirrhosis patients.
• The underlying mechanisms for this BCM increase remain unidentified but may involve alterations in insulin sensitivity and glucose metabolism.

Purpose of the Study:

• To investigate the physiological mechanisms responsible for the increase in body cell mass (BCM) following transjugular intrahepatic porto-systemic shunt (TIPS) placement in patients with liver cirrhosis.
• To assess changes in insulin sensitivity, glucose metabolism, and related hormonal profiles before and after TIPS.

Main Methods:

• Eleven patients with liver cirrhosis underwent assessment before and six months after TIPS.
• Methods included bioimpedance analyses for body cell mass, oral glucose tolerance tests, and hyperinsulinemic euglycemic clamps with tracer-determined endogenous glucose production.
• Measurements also included fasting glucose and insulin, C-peptide, insulin clearance, and levels of growth hormone, cortisol, and glucagon.

Main Results:

• Body cell mass (BCM) increased by 4.8 kg post-TIPS. Fasting insulin levels rose, and glucose intolerance worsened, indicated by increased oral glucose tolerance test areas under the curve for glucose and insulin.
• Peripheral and hepatic insulin sensitivity, assessed by glucose infusion rates and glucose tracer disappearance, remained unchanged.
• Fasting endogenous glucose production did not change and was equally suppressed by insulin, with no significant alterations in insulin clearance or counter-regulatory hormone levels.

Conclusions:

• Transjugular intrahepatic porto-systemic shunt (TIPS) insertion leads to increased body cell mass (BCM) in liver cirrhosis patients, accompanied by enhanced hyperinsulinemia and aggravated glucose intolerance.
• The anabolic effect of TIPS is not linked to improvements in insulin sensitivity, suggesting a mechanistically unexplained pathway, possibly involving reduced hepatic insulin exposure.
• The study highlights a discrepancy between BCM increase and metabolic changes, indicating that the anabolic benefits of TIPS are not mediated by improved insulin sensitivity.