Both insulin sensitivity and glucose sensitivity are impaired in patients with non-diabetic liver cirrhosis

Abstract

Background: Careful nutritional support is required in patients with liver cirrhosis due to their glucose intolerance. To elucidate the mechanism of glucose intolerance in cirrhotics, we measured insulin secretion, whole body insulin sensitivity (SI), and glucose sensitivity (SG) in non-diabetic cirrhotics. Methods: Eight patients with compensated cirrhosis who showed normal fasting blood glucose levels and non-diabetic curves on a 75 g oral glucose tolerance test participated in this study. Four normal volunteers were selected as controls. After an overnight fast, glucose was injected intravenously at 300 mg kg −1 in 2 min followed 20 min later by intravenous insulin at 0.02 U kg −1 in 5 min. Sequential blood samples were drawn from 20 min before the glucose injection to 3 h post-injection, and plasma glucose and insulin levels were determined. Plasma glucose and insulin disappearance curves were analyzed using the minimal compartment model, and kinetic parameters, including glucose clearance (KG), insulin secretion, SI and SG, were estimated. Results: KG was slower in cirrhosis than in controls, although not significant ( P=0.051). Insulin secretion was not different between the two groups. However, SI was significantly lower in cirrhotics (0.814×10 −4 min −1 pM −1; 0.572–1.403×10 −4 min −1 pM −1) as compared to controls (1.643×10 −4 min −1 pM −1; 0.678–2.085×10 −4 min −1 pM −1) ( P=0.029). SG was also lower in the cirrhosis (0.0154 min −1; 0.0071–0.0208 min −1) than in the control group (0.0211 min −1; 0.0184–0.0260 min −1) ( P=0.026). Conclusion: Both SI and SG are already impaired in non-diabetic cirrhotic patients even when KG is minimally delayed and insulin secretion has not yet been affected.