810
U N I T 9
Endocrine System
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
