الفهرس 
GLUCOREGULATION IN THE HUMAN BODYOnly 14 pages are availabe for public view
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Abstract
Glucose oxidation is a major source of energy for many cells of the body. The major pathways of glucose oxidation are Glycolysis and Krebs cycle.
Glycolysis is a series of biochemical reactions by which glucose is converted to pyruvate in aerobic condition or converted to lactate in anaerobic condition. Also amino acids are produced from intermediates of glycolysis, so glycolysis has great importance.
The Krebs citric acid is often called the final common pathway of metabolism as it provides a pathway for the oxidation of acetyl-CoA which results from glucose catabolism.
When blood glucose decreases, free glucose formed is released to the blood, as the main function of liver glycogen is to maintain blood glucose level especially during fasting or carbohydrate deficiency. This is done through Gluconeogenesis and Glycogenolysis.
The concentration of glucose in the blood is normally tightly regulated despite a significant fluctuation in supply and demand. The control of blood glucose concentration occurs via an interaction between hormonal, neural and hepatic autoregulatory mechanisms.
The human body is programmed to maintain constant homeostasis of all body systems through a complex neuroendocrine and autonomic network. Critical illness alters this homeostasis through various exaggerated autonomic and cytokine responses. The mechanisms that are impaired include glucose cellular transport, peripheral and hepatic insulin uptake.
Critically ill patients in ICU commonly enter a hyper-metabolic state, with distinct alterations in their carbohydrate metabolism as part of the physiologic stress response.
Previously, hyperglycemia was explained as an appropriate response to stress. This ‘‘diabetes of injury’’ was once considered a compensatory response that seemed to show the mandatory metabolic re-arrangements required to cope with critical stress. However, it is now being recognized as a predictor of negative outcomes in critically ill patients imposing a range of adverse effects.
The phenomenon of stress hyperglycemia results primarily from excessive release of counter regulatory hormones and cytokines; thus the sicker the patient, in general, the more likely the occurrence of elevations in blood glucose.
In the acute phase of critical illness it is assumed that the elevated levels of glucagon, cortisol and growth hormones jointly cause:
Increased hepatic Gluconeogenesis.
Hypermetabolism.
Negative nitrogen balance.
Hyperglycemia.
Hyperinsulinemia.
Insulin resistance.
Until recently, it was considered acceptable to tolerate blood glucose levels up to 220 mg/dl in fed critically ill patients. Nowadays, it is suggested by most studies that all seriously ill ICU patients with blood glucose concentrations above 150 mg per dl, should be treated with a continuous intravenous infusion of regular insulin.
Stress is more appropriately viewed as an insulin-resistant state since hyperglycemia typically occurs in the setting of a normal or increased plasma insulin concentration. However, a ’normal’ value of insulin is actually low relative to the degree of hyperglycemia.
Insulin Resistance is a condition in which defects in the action of insulin are such that normal levels of insulin do not trigger the signal for glucose absorption. The result is hyperinsulinemia to maintain euglycemia.
Insulin resistance may be expressed in many ways in critically ill patients due to many mechanisms such as:
True versus pseudo-insulin resistance.
Peripheral versus central insulin resistance.
Chronic versus acute insulin resistance.
Insulin resistance results from inherited and acquired influences. Hereditary causes include mutations of insulin receptor, glucose transporter, and signaling proteins. Acquired causes include physical inactivity, diet, medications, chronic hyperglycemia (glucose toxicity), increased free fatty acids, and the aging process.
Molecular consequences of insulin resistance can be expressed by impaired insulin signaling, inflammation and impaired fibrinolysis, while clinical consequences include hyperglycemia induced tissue damage, hypertension, dyslipidemia, metabolic syndrome and cardiovascular diseases.
Complications of insulin resistance include acute metabolic complications as severe hyperglycemia and hypoglycemia, angina, myocardial infarction, stroke, transient ischemic attack, peripheral vascular disease, renal diseases and ocular complications.
In clinical practice, no single laboratory test is used to diagnose insulin resistance. Diagnosis is based on clinical findings corborated with laboratory tests. Routine laboratory measurements in the evaluation of patients with insulin resistance syndrome include plasma glucose and glucohemoglobin levels, fasting insulin level, lipid profile, electrolyte levels, homocysteine, urine analysis, and many other laboratory studies.
The hyperinsulinemic-euglycemic clamp technique is the most scientifically sound technique for measuring insulin sensitivity, and it’s against this standard that all other tests are usually compared.
Treatment of insulin resistance can be achieved through pharmacological therapy, surgical procedures and various consultations. The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Medications that reduce insulin resistance include biguanides and thiazolidinediones, which have insulin-sensitizing and antihyperglycemic effects. Large quantities of insulin are also used in overcoming insulin resistance.