Porth's Essentials of Pathophysiology, 4e

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Diabetes Mellitus and the Metabolic Syndrome

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growth hormone levels that occur during periods of stress and periods of growth in children can produce the entire spectrum of metabolic abnormalities associated with poor regulation, despite optimized insulin treatment. Glucocorticoid Hormones. The glucocorticoid hor- mones, which are synthesized in the adrenal cortex along with other corticosteroid hormones, are critical to survival during periods of fasting and starvation. They stimulate gluconeogenesis by the liver, sometimes producing a 6- to 10-fold increase in hepatic glucose production. These hormones also moderately decrease tissue use of glucose. There are several steroid hormones with glucocor- ticoid activity; the most important of these is cortisol, which accounts for approximately 95% of all gluco- corticoid activity (see Chapter 32). Almost any type of stress, whether physical or emotional, causes an imme- diate increase in adrenocorticotropic hormone (ACTH) secretion by the anterior pituitary gland, followed within minutes by greatly increased secretion of cortisol by the adrenal gland. Hypoglycemia is a potent stimulus for cortisol secretion. In predisposed persons, the prolonged elevation of glucocorticoid hormones can lead to hyper- glycemia and the development of diabetes mellitus. In people with diabetes, even transient increases in cortisol can complicate control. ■■ The body predominantly metabolizes glucose and fatty acids for energy.The brain depends exclusively on glucose for its energy. Body tissues obtain glucose from the blood.The liver stores excess glucose as glycogen and it uses gluconeogenesis to convert amino acids, lactate, and glycerol into glucose during fasting or when glucose intake does not keep pace with demand. ■■ Blood glucose levels reflect the difference between the amount of glucose released into the circulation by the liver and the amount of glucose removed from the blood by body tissues. Fats, which serve as an efficient source of fuel for the body, are stored in adipose tissue as triglycerides, which consist of three fatty acids linked to a glycerol molecule. In situations that favor fat breakdown, such as fasting or diabetes mellitus, the triglycerides in adipose tissue are broken down and the fatty acids are used as fuel or transported to the liver, where they are converted to ketones. ■■ Proteins, which are made up of amino acids, are essential for the formation of all body structures. Unlike glucose and fatty acids, there is only a limited facility for storage of excess amino SUMMARY CONCEPTS

Diabetes Mellitus The term diabetes is derived from a Greek word mean- ing “going through,” and mellitus from the Latin word for “honey” or “sweet.” Reports of the disorder can be traced back to the first century ad , when Aretaeus the Cappadocian described the disorder as a chronic afflic- tion characterized by intense thirst and voluminous, honey-sweet urine: “the melting down of flesh into urine.” It was the discovery of insulin by Banting and Best in 1922 that transformed the once-fatal disease into a manageable chronic health problem. 7 Diabetes is a disorder of carbohydrate, protein, and fat metabolism resulting from a lack of insulin avail- ability or a reduction in the biologic effects of insulin. It can represent an absolute insulin deficiency, impaired release of insulin by the pancreatic beta cells, inadequate or defective insulin receptors or postreceptor regulation, or the production of inactive insulin or insulin that is destroyed before it can carry out its action. Classification and Etiology Although diabetes mellitus clearly is a disorder of insu- lin availability, it is not a single disease. A revised clas- sification system, which was developed in 1997 by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, divides diabetes into four clinical acids in the body. Because fatty acids cannot be converted to glucose, the body must break down proteins and use the amino acids for gluconeogenesis. ■■ Energy metabolism is controlled by a number of hormones, including insulin, glucagon, epinephrine, growth hormone, and the glucocorticoids. Of these hormones, only insulin has the effect of lowering the blood glucose level. It does this by facilitating the transport of glucose into body cells and decreasing the liver’s production and release of glucose into the bloodstream. Insulin also has the effect of decreasing lipolysis and the use of fats as a fuel source. ■■ Other hormones—glucagon, epinephrine, growth hormone, and the glucocorticoids—maintain or increase blood glucose concentrations. Glucagon and epinephrine promote glycogenolysis, and glucagon and the glucocorticoids increase gluconeogenesis. Epinephrine and glucagon also increase the use of fat for energy by increasing the release of fatty acids from adipose tissue cells. Growth hormone decreases the peripheral utilization of glucose.