Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma

Abstract

Background: Cirrhotic patients with hepatocellular carcinoma (HCC) frequently have impaired glucose metabolism.

Aims: To investigate whether impaired glucose metabolism affects the growth rate of the tumour.

Patients and methods: Tumour doubling time (DT), assessed by ultrasound imaging analysis, was measured in 60 patients with single small HCC (diameter <30 mm). DT was compared with plasma insulin and glucose concentrations following the oral glucose tolerance test (OGTT). The effect of continuous infusion of octreotide (a somatostatin analogue 200 microg/day) for three months on DT in five cases was assessed.

Results: The 60 patients were divided into two groups because the median DT was 140 days: rapid growth group (DT <or=140 days, n=30) and slow growth group (DT >140 days, n=30). Fasting plasma insulin concentration and area under the plasma insulin curve (AUC(ins)) of the OGTT (10.4 (6.2) microU/ml and 262 (152) microU/ml/h, respectively; mean (SD)) in the rapid growth group were significantly higher than those in the slow growth group (7.6 (4.3) and 146 (140), respectively) (p=0.041 and p=0.0006, respectively). In contrast, fasting plasma glucose concentration and area under the plasma glucose curve (AUC(gluc)) in the rapid growth group were significantly lower than those in the slow growth group (p=0.0003 and p=0.0012, respectively). Univariate and multivariate analyses of logistic regression models demonstrated that AUC(ins) was a significant factor contributing to the growth rate of HCC (p=0.001 and p=0.016, respectively). AUC(ins) significantly decreased after octreotide treatment (p<0.02) but AUC(gluc) did not significantly change. DT after treatment increased in three of the five patients and could not be calculated in the remaining two patients because of no change in the diameter of the tumour.

Conclusions: These data suggest that postprandial hyperinsulinaemia is associated with accelerated HCC growth.

Figure 1

Effects of octreotide on plasma insulin and glucose concentrations during the oral glucose tolerance test (OGTT) in five patients with hepatocellular carcinoma (mean (SD)). (A) Comparison of the areas under the plasma glucose curve (AUC_gluc) for the OGTT before and after octreotide treatment (NS). (B) Comparison of the areas under the plasma insulin curve (AUC_ins) for the OGTT before and after octreotide treatment (p<0.02, Wilcoxon signed ranks test).

Figure 2

Changes in doubling time of hepatocellular carcinoma before and after octreotide treatment in five patients with an area under the plasma insulin curve (AUC_ins) of ≤205 μU/ml/h or AUC_ins >205 μU/ml/h before octreotide treatment.