Mechanisms of insulin resistance in cancer associated malnutrition

This study has evaluated insulin resistance under steady-state conditions using the glucose clamp technique. Euglycaemic clamp investigations were conducted at 4-5 different insulin levels (70-1600 mUl-1) in five malnourished cancer patients, four well-nourished Intensive Care Unit patients (ICU) and 11 well-nourished individuals. Whole body uptake of glucose was measured. In three cancer patients the flux of glucose across the leg was measured. Cancer patients had significantly reduced fasting insulin concentrations, while ICU patients had increased levels compared to controls. The fasting levels of glucose did not differ among the groups. Both insulin sensitivity and responsiveness were reduced by 50% in cancer and ICU patients. At insulin levels of 200-250 mUl-1, approximately 80% of the whole body glucose uptake could be accounted for by the peripheral tissues. This study confirms that insulin resistance is a significant metabolic alteration in cancer associated malnutrition. The results demonstrate both decreased insulin sensitivity and responsiveness.