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 µg/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 <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) µU/ml and 262 (152) µU/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.

Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma

“…With regard to hepatocarcinogenesis, SSTR-2, -3, and -5 are particularly of interest. The activation of SSTR-2 and SSTR-3 leads to the inhibition of angiogenesis, cell proliferation and a reduced secretion of growth hormones (Dasgupta 2004;Garcia et al 2002;Lahlou et al 2003;Florio et al 2003;Saito et al 2002;Mazziotti et al 2002;Scharf et al 2001;Bevan 2005). Octreotide, a somatostatin analogue, can be applied for the detection and treatment of distinct tumour entities (Reubi et al 1999(Reubi et al , 2001Blaeker et al 2004;Dasgupta 2004).…”

The level of fasting serum insulin, but not adiponectin, is associated with the prognosis of early stage hepatocellular carcinoma

“…There are a few studies on the prognostic value of hyperinsulinemia on patients with HCC. Saito et al have demonstrated that the area under the plasma insulin curve for the oral glucose tolerance test can serve as a significant prognostic tool, and can assist in forecasting the doubling time of HCC (16), and that continuous infusion of octreotide in five patients inhibited insulin secretion resulting in a decrease in the HCC growth rate.…”

“…It has been reported that insulin displays growth promoting and anti-apoptotic effects on human hepatoma cells in vitro and in animal models (10,14,15). Moreover, Saito et al have ONCOLOGY REPORTS 22: 1415-1424, 2009 The level of fasting serum insulin, but not adiponectin, is associated with the prognosis of early stage hepatocellular carcinoma previously reported that postprandial hyperinsulinemia is associated with the accelerated growth of HCC (16). Recently, adiponectin, a physiologically active polypeptide secreted exclusively by adipose tissue, has been the focus of research interest as a factor involved in glucose metabolism.…”

Obesity and non-insulin-dependent diabetes mellitus in Swiss-Webster mice associated with late-onset hepatocellular carcinoma

“…Questions remain as to the role of hyperinsulinemia in carcinogenesis. High insulin levels, known hepatocyte mitogens, and growth promotants in murine and human HCC (Saito et al 2002, Boissan et al 2005 may have accelerated the growth of tumors resulting from unrelated causes or background genetic mutations. Although limited numbers of aged, nondiabetic male SW were available for study (nZ4), no gross tumors were seen in these mice or in aged nondiabetic females.…”