Porth's Essentials of Pathophysiology, 4e

810

Endocrine System

U N I T 9

insulins, which are used in combination with interme- diate or long-acting insulins, are usually administered immediately before a meal. Intermediate- to long-acting insulins (neutral protamine Hagedorn [NPH], glargine, and detemir) have slower onsets and a longer duration of action. They require several hours to reach therapeutic levels, so their use in type 1 diabetes requires supplemen- tation with rapid- or short-acting insulin. All forms of insulin have the potential to produce hypoglycemia or “insulin reaction” as a side effect (to be discussed). Two intensive treatment regimens—multiple daily injections and continuous subcutaneous infusion of insulin—closely simulate the normal pattern of insulin secretion by the body. With each method, a basal insulin level is maintained, and bolus doses of short- or rapid- acting insulin are delivered before meals. The choice of management is determined by the person with diabetes in collaboration with the health care team. With multiple daily injections (MDIs), the basal insu- lin requirements are met by an intermediate- or long- acting insulin administered once or twice daily. Boluses of rapid- or short-acting insulin are used before meals. The development of convenient injection devices (e.g., pen injectors) has made it easier for people with diabe- tes to comply with algorithms for these insulins that are administered before meals. The continuous subcutaneous insulin infusion (CSII) method uses an insulin pump. With this method, the basal insulin requirements are met by continuous infusion of subcutaneous insulin, the rate of which can be varied to accommodate diurnal variations. 38 The computer-oper- ated pump then delivers one or more set basal amounts of insulin. In addition to the basal amount delivered by the pump, a bolus amount of insulin may be delivered when needed (e.g., before a meal) by pushing a button. Although the pump’s safety has been proven, strict attention must be paid to signs of hyperglycemia. Self-monitoring of blood glucose levels is a necessity when using the CSII method of management. Hyperglycemia and ketotic episodes caused by pump failure, catheter clogging, and infections at the needle site also are possible complications. Candidate selection is crucial to the successful use of the insulin pump. Only people who are highly motivated to do fre- quent blood glucose tests and make daily insulin adjust- ments are candidates for this method of treatment. 38 Pancreas or Islet Cell Transplantation Pancreas or islet cell transplantation is not a lifesaving procedure. It does, however, afford the potential for sig- nificantly improving the quality of life. The most serious problems are the requirement for immunosuppression and the need for diagnosis and treatment of rejection. Investigators are looking for methods of transplanting islet cells and protecting the cells from destruction with- out the use of immunosuppressive drugs. 39 Management of Diabetes in Children Children with diabetes have traditionally been diag- nosed with type 1 diabetes. However, health care pro- viders are finding more children with type 2 diabetes,

a disease that has usually been diagnosed in adults aged 40 years or older. The epidemics of obesity and the low level of physical activity among young people, as well as exposure to diabetes in utero (resulting in epigenetic changes), may be major contributors to the increase in type 2 diabetes during childhood and adolescence. Children with diabetes differ from adults in many respects, including changes in insulin sensitivity related to sexual maturity and physical growth, their ability to provide self-care and their need for supervision in child care and school, and vulnerability to hypoglycemia and diabetic ketoacidosis. 11 While current standards of care for diabetes management reflect the need to main- tain glucose levels as near normal as possible, glycemic goals need to take into account that children younger than 6 or 7 years of age have a form of “hypoglycemic unawareness.” 11 Their counterregulatory mechanisms are immature and they lack the cognitive capacity to rec- ognize and respond to hypoglycemic symptoms, placing them at greater risk for hypoglycemia and its sequelae. Also, unlike adults, young children under 5 years of age are at risk for permanent cognitive impairment after episodes of severe hypoglycemia. 11 Thus, the glycemic goals for children must consider the benefits of long- term health outcomes against the risks of hypoglycemia and the difficulties in achieving normoglycemia in chil- dren. Additional concerns include the effects of drugs developed and tested primarily for adults on growth and brain development in children. Acute Complications The three major acute complications of impaired blood glucose regulation are diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), and hypogly- cemia. All are life-threatening conditions that demand immediate recognition and treatment. The Somogyi effect and dawn phenomenon, which result from the mobilization of counterregulatory hormones, contribute to difficulties with diabetic control. Diabetic Ketoacidosis Diabetic ketoacidosis, characterized by hyperglyce- mia, ketosis, and metabolic acidosis, is an acute life- threatening complication of uncontrolled diabetes. 40–42 Diabetic ketoacidosis primarily affects persons with type 1 diabetes, but may also occur in persons with type 2 diabetes when severe stress such as sepsis or trauma is present. It may be an initial manifestation of previ- ously undiagnosed type 1 diabetes or may result from increased insulin requirements in type 1 diabetes dur- ing stress situations, such as infection or trauma, that increase the release of stress hormones. For example, a mother may bring a child into the clinic or emergency department with reports of lethargy, vomiting, and abdominal pain, unaware that the child has diabetes. In clinical practice, ketoacidosis also occurs with the omission or inadequate use of insulin. Ketoacidosis reflects the effect of insulin deficiency at multiple sites (Fig. 33-10). A lack of insulin results in the