To define the influence of weight loss on the severity of metabolic abnormalities in patients with the same stage and primary site of cancer, hepatic glucose production (HGP) and nutritional status were determined in 44 patients with advanced, Stage D colorectal carcinoma and compared to values in seven cancer-free controls. The colorectal cancer patients were divided into three groups based upon percentage of ideal body weight. HGP was determined in all participants after an overnight fast by using a 3- or 4-h primed, continuous infusion of [6-3H]glucose. Fasting glucose, insulin, cortisol, thyroxine, triiodothyronine, and growth hormone values were also determined. Mean HGP was significantly elevated in colorectal carcinoma patients versus normal subjects (2.35 ± 0.89 (SD) mg/kg/min versus 1.75 ± 0.16; P < 0.01). The most severely malnourished group (ideal body weight < 90%) demonstrated the greatest increase in HGP (2.98 ± 0.73 mg/kg/min). Growth hormone mean fasting levels were significantly elevated in the colorectal carcinoma population compared to the normal subjects (2.9 ± 3.1 ng/ml versus 0.5 ± 0.2; P < 0.001). The most severely malnourished group also demonstrated the highest growth hormone levels. The rate of HGP was significantly correlated with fasting growth hormone levels (r = 0.71; P < 0.001) and not significantly correlated to cortisol, insulin, thyroxine, triiodothyronine, or glucose levels in carcinoma patients. Thus, the elevation in HGP seen in patients with colorectal carcinoma is related to the severity of weight loss and is associated with elevations in fasting growth hormone.
This work was supported in part by Clinical Nutrition Research Unit Young Investigator Award 5PO1-CA42710; NIH Grant R01-CA37320 (NCI); and Clinical Associate Physician Award, NIH General Clinical Research Center Program M01RR 00425.