Serum tumour necrosis factor alpha and insulin resistance in gastrointestinal cancer
Cancer cachexia may be mediated by endogenous peptides such as tumour necrosis factor alpha ( TNF-a). Insulin resistance occurs in these patients, and is also seen experimentally with TNF-a administration. In this study, insulin sensitivity and energy metabolism were measured in I1 patients with gastrointestinal cancer and ten controls, using the euglycaemic glucose clamp and indirect calorimetry. Patients with cancer were significantly more insulin resistant than controls (P < 0.01) and in such patients insulin resistance correlated with serum TNF-u level (rs = 0.74, P < 0.01). Fasting insulin levels also correlated inversely with insulin sensitivity (rs = -0.62, P = 0.003). These results suggest a possible association between endogenous TNF-a production and insulin resistance in patients with gastrointestinal cancer.
Malnutrition caused by mechanical obstruction of the gastrointestinal tract, loss of appetite and abnormalities of host metabolism is common in gastrointestinal cancer'. Aberrations of carbohydrate, fat and protein metabolism have been described in detail in the cancer-bearing host', with resistance to the anabolic effects of insulin playing a prominent role. These abnormalities may be mediated indirectly by endogenous peptides, such as tumour necrosis factor alpha (TNF-a), activated during immune and inflammatory responses to a variety of stimuli'. TNF-a fulfils Koch's postulates as a mediator of fatal sepsis4 and has also been implicated, when produced in lesser amounts, as a possible mediator of cancer-associated cachexia5.
The euglycaemic glucose clamp (EGC) is an established method of assessing insulin resistance in u i v d . The aim of this study was to measure insulin resistance and energy metabolism in patients with gastrointestinal cancer and correlate these with circulating TNF-cr levels.