Insulin resistance and body composition in cancer patients.

Cancer cachexia, weight loss with altered body composition, is a multifactorial syndrome propagated by symptoms that impair caloric intake, tumor byproducts, chronic inflammation, altered metabolism, and hormonal abnormalities. Cachexia is associated with reduced performance status, decreased tolerance to chemotherapy, and increased mortality in cancer patients. Insulin resistance as a consequence of tumor byproducts, chronic inflammation, and endocrine dysfunction has been associated with weight loss in cancer patients. Insulin resistance in cancer patients is characterized by increased hepatic glucose production and gluconeogenesis, and unlike type 2 diabetes, normal fasting glucose with high, normal or low levels of insulin. Cancer cachexia results in altered body composition with the loss of lean muscle mass with or without the loss of adipose tissue. Alteration in visceral adiposity, accumulation of intramuscular adipose tissue, and secretion of adipocytokines from adipose cells may play a role in promoting the metabolic derangements associated with cachexia including a proinflammatory environment and insulin resistance. Increased production of ghrelin, testosterone deficiency, and low vitamin D levels may also contribute to altered metabolism of glucose. Cancer cachexia cannot be easily reversed by standard nutritional interventions and identifying and treating cachexia at the earliest stage of development is advocated. Experts advocate for multimodal therapy to address symptoms that impact caloric intake, reduce chronic inflammation, and treat metabolic and endocrine derangements, which propagate the loss of weight. Treatment of insulin resistance may be a critical component of multimodal therapy for cancer cachexia and more research is needed.