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BIOC33H3 (127)

Diabetes Mellitus

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Biological Sciences
Stephen Reid

Chapter 49: Diabetes Mellitus  Diabetes mellitus is a chronic multisystem disorder of glucose metabolism related to absent or insufficient insulin supplies and/or poor utilization of the insulin that is available.  The two most common types of diabetes are classified as type 1 or type 2 diabetes mellitus. Gestational diabetes, prediabetes, and secondary diabetes are other classifications of diabetes commonly seen in clinical practice. TYPE 1 DIABETES  Type 1 diabetes mellitus most often occurs in people who are under 30 years of age, with a peak onset between ages 11 and 13, but can occur at any age.  Type 1 diabetes is the end result of a long-standing process where the body’s own T cells attack and destroy pancreatic beta cells, which are the source of the body’s insulin.  Because the onset of type 1 diabetes is rapid, the initial manifestations are usually acute. The classic symptoms are polyuria, polydipsia, and polyphagia.  The individual with type 1 diabetes requires a supply of insulin from an outside source (exogenous insulin), such as an injection, in order to sustain life. Without insulin, the patient will develop diabetic ketoacidosis (DKA), a life-threatening condition resulting in metabolic acidosis. PREDIABETES  Prediabetes is a condition where blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes. Most people with prediabetes are at increased risk for developing type 2 diabetes and if no preventive measures are taken, they will usually develop it within 10 years.  Long-term damage to the body, especially the heart and blood vessels, may already be occurring in patients with prediabetes. TYPE 2 DIABETES  Type 2 diabetes mellitus is, by far, the most prevalent type of diabetes, accounting for over 90% of patients with diabetes.  In type 2 diabetes, the pancreas usually continues to produce some endogenous (self-made) insulin. However, the insulin that is produced is either insufficient for the needs of the body and/or is poorly used by the tissues.  The most important risk factors for developing type 2 diabetes are believed to be obesity, specifically abdominal and visceral adiposity. Also, individuals with metabolic syndrome are at an increased risk for the development of type 2 diabetes.  Some of the more common manifestations associated with type 2 diabetes include fatigue, recurrent infections, recurrent vaginal yeast or monilia infections, prolonged wound healing, and visual changes. GESTATIONAL DIABETES  Gestational diabetes develops during pregnancy and is detected at 24 to 28 weeks of gestation, usually following an oral glucose tolerance test.  Although most women with gestational diabetes will have normal glucose levels within 6 weeks postpartum, their risk for developing type 2 diabetes in 5 to 10 years is increased.  A diagnosis of diabetes is based on one of three methods: (1) fasting plasma glucose level, (2) random plasma glucose measurement, or (3) 2-hour oral glucose tolerance test.  The goals of diabetes management are to reduce symptoms, promote well-being, prevent acute complications of hyperglycemia, and prevent or delay the onset and progression of long-term complications. These goals are most likely to be met when the patient is able to maintain blood glucose levels as near to normal as possible. INSULIN THERAPY  Exogenous (injected) insulin is needed when a patient has inadequate insulin to meet specific metabolic needs.  Insulin is divided into two main categories: short-acting (bolus) and long-acting (basal) insulin. Basal insulin is used to maintain a background level of insulin throughout the day and bolus insulin is used at mealtime.  A variety of insulin regimens are recommended for patients depending on the needs of the patient and their preference.  Routine administration of insulin is most commonly done by means of subcutaneous injection, although intravenous administration of regular insulin can be done when immediate onset of action is desired.  The technique for insulin injections should be taught to new insulin users and reviewed periodically with long-term users.  The speed with which peak serum concentrations are reached varies with the anatomic site for injection. The fastest absorption is from the abdomen.  Continuous subcutaneous insulin infusion can be administered using an insulin pump, a small battery-operated device that resembles a standard paging device in size and appearance. The device is programmed to deliver a continuous infusion of rapid-acting or short-acting insulin 24 hours a day and at mealtime, the user programs the pump to deliver a bolus infusion of insulin.  An alternative to injectable insulin is inhaled insulin. Exubera is a rapid-acting, dry powder form of insulin that is inhaled through the mouth into the lungs prior to eating via a specially designed inhaler.  Hypoglycemia, allergic reactions, lipodystrophy, and the Somogyi effect are problems associated with insulin therapy. o Lipodystrophy (atrophy of subcutaneous tissue) may occur if the same injection sites are used frequently. o The Somogyi effect is a rebound effect in which an overdose of insulin induces hypoglycemia. Usually occurring during the hours of sleep, the Somogyi effect produces a decline in blood glucose level in response to too much insulin. o The dawn phenomenon is characterized by hyperglycemia that is present on awakening in the morning due to the release of counterregulatory hormones in the predawn hours. ORAL AGENTS  Oral agents (OAs) are not insulin, but they work to improve the mechanisms by which insulin and glucose are produced and used by the body. OAs work on the three defects of type 2 diabetes, including (1) insulin resistance, (2) decreased insulin production, and (3) increased hepatic glucose production.  Sulfonylureas are frequently the drugs of choice in treating type 2 diabetes due to the decreased chance of prolonged hypoglycemia. The primary action of the sulfonylureas is to increase insulin production from the pancreas.  Like the sulfonylureas, meglitinides increase insulin production from the pancreas. But because they are more rapidly absorbed and eliminated, they offer a reduced potential for hypoglycemia.  Metformin (Glucophage) is a biguanide glucose-lowering agent. The primary action of metformin is to reduce glucose production by the liver.  α-Glucosidase inhibitors, also known as “starch blockers,” these drugs work by slowing down the absorption of carbohydrate in the small intestine.  Sometimes referred to as “insulin sensitizers,” thiazolidinediones are most effective for people who have insulin resistance. They improve insulin sensitivity, transport, and utilization at target
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