Hormonal Response to Injury Infection and Cancer

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Infection, cancer, or any injury to the body result in an increase in counterregulatory hormones as well as insulin concentration. As a result of cancer, sepsis, or injury, many patients develop the syndrome of insulin resistance even though they had no history of diabetes prior to cancer. In cancer patients, when the overall injury is smaller, many studies have failed to demonstrate an elevation in counterregula-tory hormones. Mild elevations in cortisol concentrations may contribute to the protein catabolism and increased gluconeogenesis. When serum insulin is measured with a sensitive assay, cancer patients demonstrate a small but significant elevation in serum insulin concentration. This is consistent with the observation that these patients have insulin resistance. Cancer patients, like diabetics, have a reduced glucose utilization and loss of the first-phase insulin response, and many have an increased fasting hepatic glucose production rate. As mentioned previously, underweight cancer patients frequently have increased fatty acid oxidation and plasma fatty acid appearance rates. Triglyceride hydrolysis involves much more than fat oxidation, so albumin-bound fatty acids are used partially for energy but many are utilized for reesterification or substrate cycling back to triglyceride.

The rise in serum cortisol as the host's response to the tumor is one of many factors that are responsible for the development of insulin resistance. Insulin resistance is easy to diagnosis because the patient's fasting glucose will be elevated. An elevated fasting glucose level of approximately 110mg/dl is a good marker of insulin resistance. This is not likely seen in mild injury alone unless the patient has a predisposition to the development of diabetes mellitus. Although insulin resistance is present, the presence of frank diabetes (blood glucose level >126mg/dl or >7 mm) is not common in cancer or mild injury. It is more common in patients with severe infection or injury. Although most of the counterregulatory hormones are usually normal, serum cortisol and/or glucagon can be mildly elevated. Newer glucagon assays measure the normal value as 35-45 ng/ml, so a significant increase in injury can be detected, which was difficult to do with the older Unger assay. Recent data from pancreatic cancer patients have shown elevated glucagon concentrations, which may be contributing to the development of diabetes. Earlier work found that GH secretion was increased in cancer patients by 24-h analysis and by random sampling. However, after careful study, the increase in GH does not appear to have a major influence on hepatic glucose metabolism. Although there may be a small effect on glycogen breakdown, the major effect is likely via inhibition of glucose utilization in the skeletal muscle.

The sick euthyroid state, in which total tri-iodothyronine (T3) concentrations are reduced in severely injured and infected patients, is common. This is likely a normal response to conserve energy in the injured person as the body's ability to convert the stored form of a thyroid hormone (thyroxine (T4)) into the active form of thyroid hormone, T3, becomes impaired. T4 is converted to an inactive thyroid hormone known as reverse-T3 hormone (rT3). This event may have evolved as a necessary energy-saving response during a severe injury or illness to reduce the known contribution of T3 to resting energy expenditure. The low T3 syndrome is an adaptive way to reduce the normal day-today effect of T3 on resting energy expenditure. This process can occur in the aggressive cancers, for which the patient's response is similar to that of an injury response.

In septic and injured patients, all counterregulatory hormones are routinely elevated, contributing to an increase in protein catabolism, glucose production, gluconeogenesis, and glycogen breakdown and a major reduction in glucose utilization and anabolism.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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