The Mechanism of the Carbohydrate Intolerance of Cirrhosis*

Abstract

Cirrhosis of the liver is frequently associated with carbohydrate intolerance but it is unknown whether this intolerance is due to increased hepatic glucose production (HGP), decreased glucose utilization, or both. HGP and the MCR of glucose [(MCR)G] were measured at steady state, basally and during an infusion of insulin (25 mU/kg x h) and glucose (11 mumol/kg x min), in 11 cirrhotics and 8 controls using the technique of a primed constant infusion of [3H]3-glucose. HGP was also estimated at nonsteady state during an infusion of glucagon (8 ng/kg x min). Basal HGP was significantly lower in cirrhotics compared to controls (10.2 +/- 0.6 vs. 13.2 +/- 0.6 mumol/kg x min; P < 0.0025). During the insulin/glucose infusion, HGP was suppressed to the same degree in both groups [in controls by 83% (13.2 +/- 0.6 to 2.2 +/- 0.8 mumol/kg x min) and in cirrhotics by 87% (10.2 +/- 0.6 to 1.3 +/- 0.4 mumol/kg x min)]. After the glucagon infusion, HGP rose by a similar degree in cirrhotics and controls. In contrast, basal (MCR)G was significantly lower in the nondiabetic cirrhotics (2.1 +/- .02 ml/kg x min; P < 0.005) and diabetic cirrhotics (1.2 +/- 0.2 ml/kg x min; P < 0.0005) compared to that in the control subjects (2.8 +/- 0.2 ml/kg x min). Moreover, there was a highly significant (P < 0.001) negative correlation between basal (MCR)G and the fasting glucose level (r = 0.82), and the degree of glucose intolerance as expressed by the 2-h glucose level determined by the oral glucose tolerance test (r = 0.87). It is concluded that the glucose intolerance of cirrhosis is due to a defect in peripheral glucose utilization.

Indirect Calorimetry and Anthropometry to Estimate Energy Metabolism in Patients with Liver Cirrhosis

“…Decrease in glucose oxidation in cirrhosis is explained by the lower production rate of glucose from glycogen (24), decrease in peripheral glucose use (24), and decrease in hepatic glycogen stores (25). In the present study, npRQ correlated significantly with %AC and %AMC.…”

Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients

“…The insulin infusion rate used during the euglycaemic clamp was considerably higher than that shown to completely suppress HGO in both control subjects and non-diabetic cirrhotic patients [45,46]. Both methods confirmed the presence of marked insulin resistance in the non-diabetic cirrhotic patients and there was a strong correlation between indices of insulin sensitivity derived by the two methods, suggesting that the minimal model provides a useful measure of insulin sensitivity in cirrhosis.…”

Liver transplantation in cirrhotic patients with diabetes mellitus: Midterm results, survival, and adverse events

“…Patients with pre-OLT DM not requiring treatment also had a greater incidence of post-OLT DM during the first year, but the difference between these patients and those without DM lost its significance later. Post-OLT DM was very infrequent in patients without DM before OLT, and none of the patients with normal OGTT results had post-OLT DM at any of the times studied (3,12,24, and 36 months). As shown, the incidence of post-OLT DM is greatest in the early post-OLT period, probably because of the greater doses of immunosuppressive drugs used during this period and the persistence of some degree of portasystemic shunting.…”

“…[1][2][3] Insulin resistance has been found in most patients with cirrhosis. [4][5][6] It seems to be caused mainly by a deficiency in insulin-stimulated glycogen synthesis in the muscle.…”