TYPE 1 DIABETES MELLITUS

Type 1 diabetes mellitus is a disorder that involves an absolute or relative deficiency of insulin, which is
in contrast to type 2, where insulin production is only reduced. Type 1 diabetes is equal in incidence in
boys and girls and affects approximately 1 of every 500 children and adolescents in the United States
(Sherr & Weinzimer, 2012).

Etiology

The disease apparently results from immunologic damage to islet cells in susceptible individuals. Why
autoimmune destruction of islet cells occurs is unknown, but children with the disorder have a high
frequency of certain human leukocyte antigens (HLAs), particularly HLA-DR3 and HLA-DR4, located
on chromosome 6, that may lead to susceptibility. If one child in a family has diabetes, the chance that a
sibling will also develop the illness is higher than in other families because siblings also tend to have one
of the specific HLA that are associated with the disease

Pathophysiology

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder characterized by the destruction of insulin-
producing beta cells in the pancreas. The pathophysiology of T1DM involves several key processes:

1. Autoimmune response: In individuals with a genetic predisposition, an autoimmune response is

triggered, leading to the destruction of beta cells in the islets of Langerhans within the pancreas.
The exact cause of this autoimmune response is not fully understood but is believed to involve a
combination of genetic and environmental factors.

2. Destruction of beta cells: Immune cells, particularly T lymphocytes, infiltrate the pancreatic
islets and initiate an attack on the beta cells. This immune-mediated destruction leads to a
significant reduction in insulin production.

3. Insulin deficiency: As the beta cells are progressively destroyed, insulin production decreases.
Insulin is a hormone responsible for regulating blood glucose levels by facilitating the uptake of
glucose into cells. The deficiency of insulin in T1DM results in elevated blood glucose levels
(hyperglycemia) as glucose cannot enter cells effectively.

4. Hyperglycemia and glucosuria: With insufficient insulin, glucose remains in the bloodstream,
leading to hyperglycemia. The kidneys attempt to filter out the excess glucose, but when blood
glucose levels exceed the renal threshold, glucose spills into the urine (glucosuria). This leads to
increased urine production (polyuria) and increased thirst (polydipsia).

Management of T1DM typically involves exogenous insulin administration, frequent blood

glucose monitoring, carbohydrate counting, and lifestyle modifications to maintain stable blood
glucose levels and prevent complications.
Disease Process

Insulin acts as a key that allows glucose to enter body cells for energy. However, certain cells, including
those in the brain, erythrocytes, leukocytes, intestinal mucosa, and kidney epithelium, can function
without insulin for glucose transport. In the absence of insulin, glucose accumulates in the bloodstream,
leading to hyperglycemia. The kidneys respond to hyperglycemia by excreting excess glucose into the
urine, causing glycosuria and fluid loss (polyuria). The loss of fluid triggers thirst (polydipsia), resulting
in the three main symptoms of diabetes: polyuria, polydipsia, and hyperglycemia. Since cells can't utilize
glucose, the body starts breaking down protein and fat for energy. Metabolizing fat leads to weight loss,
elevated levels of ketone bodies in the bloodstream (resulting in high serum cholesterol levels and
ketoacidosis), and the presence of ketones in the urine. Potassium and phosphate, acting as buffers, leave
cells and are excreted, causing an electrolyte imbalance. Untreated diabetic children experience weight
loss, acidosis from ketone accumulation, dehydration, and an electrolyte imbalance. Inadequate glucose
utilization for energy hinders proper growth, resulting in stunted growth and underweight.

Assessment

Although children may be prediabetic for some time, the onset of symptoms in childhood is usually
abrupt. Parents notice increased thirst and increased urination (which may be recognized first as bed-
wetting [enuresis] in a previously toilet-trained child). The dehydration may cause constipation.

Laboratory Studies

In some children, diabetes is detected at a routine health screening. For others, although the disease has
been progressing internally for some time, outward symptoms have such an abrupt onset that the child is
in a coma from acidosis and hyperglycemia by the time it is detected. Laboratory studies usually show a
random plasma glucose level greater than 200 mg/dl (normal range, 70 to 110 mg/dl fasting; 90 to 180
mg/dl not fasting) and significant glycosuria

Two diagnostic tests, the fasting blood glucose test and the random blood glucose test, are used to
confirm diabetes. A diagnosis of diabetes is established if one of the following three criteria is present on
two separate occasions:

• Symptoms of diabetes plus a random blood glucose level greater than 200 mg/dl

• A fasting blood glucose level greater than 126 mg/dl

• A 2-hour plasma glucose level greater than 200 mg/dl during a 75-g oral glucose tolerance test (GTT)

Typically, a GTT involves the oral ingestion of a concentrated glucose solution followed by blood
glucose levels drawn at fasting (baseline), after 1 hour, and after 2 hours. The test is difficult for children
to undergo because it requires them to fast for 8 2967 hours, drink an overly sweet solution, and submit to
painful, intrusive procedures (routine application of lidocaine/prilocaine [EMLA] cream to finger stick or
venipuncture sites and use of intermittent infusion devices greatly reduces this problem). Do not take
blood for glucose analysis from functioning IV tubing to try to help with pain because the glucose in the
IV solution will cause the serum reading to be abnormally high.

Other Diagnostic Tests

If diabetes is detected, the diagnostic workup also usually includes an analysis of blood samples for pH,
partial pressure of carbon dioxide (PCO2 ), sodium, and potassium levels; a white blood cell count; and a
glycosylated hemoglobin (HbA1c) evaluation. Normally, the hemoglobin in red blood cells carry only a
trace of glucose. If serum glucose is excessive, however, excess glucose attaches itself to hemoglobin
molecules, creating HbA1c. In nondiabetic children, the usual HbA1c value is 1.8 to 4.0. A value greater
than 6.0 reflects an excessive level of serum glucose. Measuring HbA1c has advantages because it not
only provides information on what is the child’s present serum glucose level but what the serum glucose
levels have been during the preceding 3 to 4 months (red blood cells have a life span of 120 days).

If the potassium level of the blood is low, a child may need an electrocardiogram to observe for T-wave
abnormalities, the mark of potassium deficiency. The white blood cell count of a child with diabetes may
be elevated even though no infection is present, apparently as a response to the ketoacidosis. The
presence of infection must always be suspected, however, because it is often a precipitant to a diabetic
crisis. For this reason, nose and throat cultures may be obtained as well.

Therapeutic Management

Therapy for children with type 1 diabetes involves insulin administration, regulation of nutrition and
exercise, stress management, and monitoring blood glucose and urine ketone levels. Upon diagnosis,
children are usually admitted to the hospital for approximately 3 days for extensive education and care.
Initially, insulin is administered intravenously (IV) at a dose of 0.1 to 0.2 units per kilogram of body
weight per hour to correct hyperglycemia and ketoacidosis. Once the blood glucose level falls below 200
mg/dl, the IV insulin infusion is gradually reduced. Regular insulin is typically used for emergency
replacement due to its fast-acting properties. Glucose may also be added to the infusion to prevent further
breakdown of fats and protein. After 24 hours, oral feedings can replace the IV route as the child's serum
glucose levels normalize. Management in the following days is guided by serum glucose determinations.
The child may transition to subcutaneous injections of regular insulin alone for the first 1 or 2 days and
then introduce intermediate-acting insulin when oral fluids are tolerated, usually on the second day of
therapy.

Insulin Administration

Types of insulin vary as to their time of onset, peak action, and duration of action (Table 48.4). Children
can be regulated on a variety of insulin programs, but typically receive a combined insulin dose of 0.4 to
0.7 units per kilogram of body weight daily in two divided doses (one before breakfast and one before
dinner); adolescents may need as much as 1.2 units per kilogram daily divided into the two doses. The
most common mixture of insulin used with children is a combination of an intermediate-acting insulin
and a regular insulin, usually in a 2:1 ratio or 0.75 units of the intermediate-acting insulin to 0.33 units
regular insulin, and given in the same syringe, although this prescription varies for individual children.
The morning dose is two thirds of the total daily dose; the evening dose is the remaining one third.
The advantage of using two different types of insulin

Using two different types of insulin in a child with diabetes offers the advantage of having peak effects at
different times. Short-acting insulins peak around 3 to 4 hours after administration, providing maximum
effect between 10 AM and 12 noon when taken before breakfast. Intermediate-acting insulin, on the other
hand, peaks around 8 to 14 hours after administration, typically in the late afternoon, just before dinner.
These peak times are crucial to remember as they are when a child is most likely to experience symptoms
of hypoglycemia. Some children may require three or four daily insulin injections to prevent
hyperglycemia, allowing for greater flexibility in activity and calorie consumption. Parents are educated
on insulin algorithms or protocols that consider their child's activity level and meal size, allowing for
adjustments in insulin doses. The time between insulin injection and a meal is called "lag time," and it can
be increased to prevent hyperglycemia if the premeal blood glucose is above the target range or decreased
to prevent hypoglycemia if the blood glucose is low. Insulin glargine (Lantus) is a long-acting insulin that
lasts 24 hours and can be used in combination with three doses of regular insulin before meals to regulate
glucose levels. However, it cannot be mixed with other insulins due to its low pH.

Insulin Pumps

An insulin pump is an automatic device approximately the size of an iPhone. It delivers insulin at a
constant rate, so it regulates serum glucose levels better than periodic injections (Buchko, Artz, Dayhoff,
et al., 2012). To use a pump, a syringe of regular insulin is placed in the pump chamber; a length of thin
polyethylene tubing leads to the child’s abdomen, where it is implanted into the subcutaneous tissue of
the abdomen by a small-gauge needle. Women who develop gestational diabetes also use insulin pumps;
therefore, these are illustrated and the care is described in Chapter 20. Most children adjust well to pump
therapy and prefer it to daily injections.

Inhalation Insulin

Inhalation insulin is not available as yet but may be in the future; production of it is in experimental trials.
Difficulties with development are constructing an accurate delivery system and determining how the
development of a cold or allergies that cause edema of the nasal membrane will affect drug absorption
(Boss, Petrucci, & Lorber, 2012).

Nutrition

In order to know how much insulin to give before a meal, parents need to learn to count the total
carbohydrate amount in food by carefully reading food labels. An insulin-to[1]carbohydrate ratio is then
calculated individually for each child depending on age and activity to guide insulin administration. For
example, if a child is prescribed an insulin[1]to-carbohydrate ratio of 1 unit of insulin to each 10 g of
carbohydrates and the meal the child will be served contains 50 g carbohydrates, the parent would
administer 5 units of regular insulin before the meal. An overall meal pattern should include three spaced
meals that are high in fiber plus a snack in the midmorning, midafternoon, and evening to keep
carbohydrate amounts as level as possible during the day. Most parents need to meet with a nutritionist to
discuss what a “meal high in fiber” means, how to become adept at carbohydrate counting, and what
meals are best to serve to their age child.

Self-Monitoring of Blood Glucose

Children as young as early school age can learn the techniques of finger puncture and reading a
computerized monitor. Using a spring-loaded injection pen helps minimize pain; an automatic readout
monitor simplifies the procedure (Fig. 48.8). Children are adolescents, however, before they can be
counted on to independently monitor their serum glucose levels on a daily basis.

Urine Testing

Urine testing is not used routinely but is used to test for ketonuria if the child develops a gastrointestinal
“flu” and is not able to eat. Acetone revealed by a test strip is a sign fat is being used for energy or that
the child is becoming acidotic.

The “Honeymoon” Period

After a child’s diagnosis has been confirmed and the blood glucose level has been initially regulated by
insulin, a honeymoon period may follow, during which only a minimal amount of insulin, or none at all,
is needed for glucose regulation. This apparently occurs because the exogenous insulin stimulates the islet
cells to produce a small amount of natural insulin, as if they are being reminded of their function. After a
month or even up to a year, however, the islet cells will begin to fail once again, and diabetic symptoms
will recur. This can be upsetting to parents if they began to believe their child was wrongly diagnosed or
that a cure had taken place. Caution both the parents and the child that symptoms will inevitably recur.

Stress Adjustment

Whenever children with diabetes undergo a stressful situation, either emotionally or physically, they may
need increased insulin to maintain glucose homeostasis. When children are seen at healthcare facilities for
periodic checkups, ask them whether they are having any difficulty with blood testing or insulin injection
and how things are at home and at school to detect their stress level.

Try to interview children separately from their parents, so they can feel free to talk about anything that
may be happening or going wrong. If a child is experiencing stress because of school, parents may have
to meet with school officials to help them view the child as well, not ill, so that they will allow
participation in all activities, including sports. Sometimes, children are embarrassed to have to do blood
glucose testing in school, especially in a public lavatory. It may be easier for them if they can go to the
nurse’s office for privacy when testing.

Complications
 If an infection occurs and the child’s temperature rises, insulin resistance increases, causing a need for
additional insulin. Teach parents to notify their primary healthcare provider if their child appears to be ill
(particularly if the child is nauseated or vomiting) for careful observation and a change in insulin dosage
if necessary. If a child with diabetes is scheduled for surgery, careful regulation on the day of surgery and
in the immediate postoperative period is essential, especially if oral fluids will be restricted.

Many long-term body changes such as arteriosclerosis (hardening of artery walls), which can lead to
general poor circulation and kidney disease, and thickening of retinal capillaries and cataract formation,
which ultimately can result in blindness, occurring because of chronic hyperglycemia, are not a major part
of disease management in childhood because their onset does not begin until adulthood. It is not too early,
however, when discussing hyperglycemia to mention that it does have long-term effects if not regulated
beginning in childhood.

Type 2 Diabetes Mellitus (T2D)

Type 2 DM is a separate disease from type 1 diabetes and is not caused by autoimmune factors. While it
was traditionally seen in older adults, T2D is now observed in overweight school-aged children as well.
Risk factors for T2D include a strong family history of diabetes, certain ethnic backgrounds, poor diet
high in fats and carbohydrates, lack of regular exercise, and the development of polycystic ovary
syndrome (PCOS). Symptoms of T2D often become apparent during puberty due to increased insulin
resistance caused by sex hormones. Common symptoms include glucose in urine, acanthosis nigricans
(dark shiny patches on the skin), and reduced thirst or increased urination. Screening with a fasting blood
sugar test is recommended for children with a family history of T2D, susceptible genetic groups,
symptoms such as acanthosis nigricans or high blood pressure, and should be repeated every two years.
Although the pancreatic islet cells in T2D can still produce some insulin, therapy primarily involves
nutrition and exercise, similar to type 1 diabetes, along with oral antiglycemic agents like metformin.
T2D is a chronic condition that persists into adulthood and can lead to complications such as
atherosclerosis, kidney disease, poor wound healing, and vision problems. Proper management and
education are crucial in preventing hyperglycemia and its associated vascular complications, allowing
individuals with T2D to lead healthy lives whether at home or away from home.

The Parathyroid Glands

The four parathyroid glands, located posterior and adjacent to the thyroid gland, regulate serum levels of
calcium in the body by controlling the rate of bone metabolism through the secretion of parathyroid
hormone. This hormone is unique in that it is not under the control of the pituitary gland but rather is
controlled by negative feedback from the circulating serum levels of calcium and how much vitamin D is
present to allow absorption of calcium from the gastrointestinal tract into the bloodstream.

HYPOCALCEMIA

Hypocalcemia is a lowered blood calcium level that occurs to some extent in all newborns before they
begin sucking well. It occurs because phosphorus and calcium levels are always maintained in an inverse
proportion to each other in the bloodstream (if phosphorus levels rise, calcium levels decrease, and vice
versa). Hypocalcemia may be caused, therefore, by a change in either calcium or phosphorus metabolism
(Thomas, Smith, White, et al., 2012).
Assessment

Hypocalcemia tends to occur in infants who experienced birth anoxia (phosphorus is released with
anoxia), in immature infants (the parathyroid glands are immature), and in infants of women with diabetes
(it tends to accompany the hypoglycemia that occurs in these infants shortly after birth).

The chief sign of hypocalcemia is neuromuscular irritability, referred to as latent tetany. This occurs if the
blood calcium level falls below 7.5 mg/dl. The newborn will demonstrate jitteriness when handled or if
the infant has been crying for an extended period.

Four methods are used to produce the clinical manifestations of tetany for diagnosis, as shown in Table
48.6. Any of these tests are helpful in determining whether a newborn’s jitteriness is a result of
hypocalcemia or a central nervous system concern.

Pathophysiology

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and
impaired insulin secretion. The pathophysiology of T2DM involves multiple interconnected factors:

1. Insulin resistance: The primary defect in T2DM is insulin resistance, in which cells in the body
become less responsive to the effects of insulin. As a result, glucose uptake by cells is impaired,
leading to elevated blood glucose levels. Adipose tissue, particularly visceral fat, releases
increased levels of free fatty acids, which contribute to insulin resistance.

2. Impaired insulin secretion: In addition to insulin resistance, individuals with T2DM often have
reduced insulin secretion by the beta cells of the pancreas. The exact mechanism for this impaired
secretion is not fully understood, but it is thought to involve dysfunction and loss of beta cell
mass over time.

3. Hyperglycemia and glucotoxicity: Insulin resistance and impaired insulin secretion result in
chronic hyperglycemia. Persistently elevated blood glucose levels can further damage pancreatic
beta cells, exacerbating insulin secretion impairment. This vicious cycle is known as
glucotoxicity.

4. Dysregulated hepatic glucose production: In T2DM, the liver may overproduce glucose,
contributing to hyperglycemia. Insulin normally suppresses hepatic glucose production, but in
T2DM, this regulation is disrupted.

5. Incretin dysfunction: Incretins are hormones released by the gut after a meal, such as glucagon-
like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). They enhance
insulin secretion and suppress glucagon release, helping to regulate blood glucose levels. In
T2DM, there is a reduction in incretin-mediated effects, leading to inadequate insulin response
after meals.

6. Adipokine imbalance: Adipose tissue secretes various bioactive substances called adipokines,
which play a role in regulating metabolism. In T2DM, there is an imbalance of adipokines, with
 increased release of pro-inflammatory adipokines (such as tumor necrosis factor-alpha) and
reduced release of anti-inflammatory adipokines (such as adiponectin). This imbalance
contributes to insulin resistance and systemic inflammation.

7. Genetic and environmental factors: Both genetic and environmental factors contribute to the
development of T2DM. Genetic predisposition can influence insulin sensitivity, insulin secretion,
and other metabolic processes. Environmental factors, such as sedentary lifestyle, poor dietary
choices, obesity, and chronic stress, can further promote insulin resistance and beta cell
dysfunction.

Understanding the pathophysiology of T2DM is crucial because it guides the management and treatment
of the condition. By targeting the underlying mechanisms, healthcare providers can develop
individualized treatment plans to improve insulin sensitivity, enhance insulin secretion, and regulate
blood glucose levels. Lifestyle modifications, such as regular physical activity, a healthy diet, weight
management, and stress reduction, are essential in managing T2DM. Medications that address insulin
resistance, stimulate insulin secretion, and regulate glucose metabolism are also commonly prescribed.
Furthermore, understanding the pathophysiology helps in the development of new therapeutic approaches
and strategies for preventing and managing T2DM-related complications, such as cardiovascular disease,
kidney dysfunction, and neuropathy.

Therapeutic Management

Treatment is aimed at increasing the calcium level in the blood above the point of latent tetany. This can
be administered orally as 10% calcium chloride if the infant can and will suck. Otherwise, it will be given
IV as a 10% solution of calcium gluconate. Newborns who are having generalized seizures may require
anticonvulsant therapy in addition to the calcium gluconate to halt the seizures. Emergency equipment for
intubation to relieve laryngospasm should be available.

After immediate therapy to increase the low blood calcium levels, infants are given oral calcium therapy
until their calcium level stabilizes at greater than 7.5 mg/dl. Because vitamin D is necessary for the
absorption of calcium from the gastrointestinal tract, the infant also may be given a vitamin D supplement
such as calcitriol.

Metabolic Disorders (Inborn Errors of Metabolism)

Many causes of hormonal deficiency or excess in children are not related to the endocrine glands and the
highly complex system of feedback and communication between these glands and the pituitary but rather
are due to inherited biochemical disorders that disrupt the metabolism of amino acids, proteins,
carbohydrates, or lipids. Many of these disorders are evident at or soon after birth and can cause
irreversible cognitive challenge and early death, making early detection and treatment crucial. Gene
therapy is expected to be available in the future to reverse symptoms of these disorders (van Karnebeek &
Stockler, 2012).

Assessment
 Early identification of the disorder is essential to prevent the child from becoming severely cognitively
challenged. Because of this, all infants in the United States are screened at birth by blood spot analysis
after receiving 2 full days of breast or formula feedings. If an infant is born at home or is discharged from
a hospital or birthing center before the second day of life, remind the parents to have the test performed
on the second or third day after birth. If a newborn did not suck well, so there is a question as to whether
the baby received adequate milk for the test to be effective, the test can be repeated at the second week of
life during a healthcare visit.

Therapeutic Management

Phenylketonuria (PKU) is primarily managed through dietary restriction, which has been the main
treatment for over 50 years. Large neutral amino acids and the drug sapropterin (Kuvan) have been
suggested as alternative treatments. Infants diagnosed with PKU are placed on a formula low in
phenylalanine, and breastfeeding may be limited to provide some phenylalanine. As the child grows
older, providing adequate nutrition becomes challenging due to the absence of natural proteins with low
phenylalanine levels. Dietary management involves balancing the child's nutritional needs while keeping
blood phenylalanine levels low. Foods high in protein, such as meats, eggs, and milk, are high in
phenylalanine, while foods low in phenylalanine include orange juice, bananas, potatoes, lettuce, spinach,
and peas. Special formulas like Lofenalac can be used to prepare treat foods. Regular monitoring of blood
and urine phenylalanine levels, as well as hemoglobin levels to detect anemia, is essential. Obesity
screening is necessary due to the high carbohydrate content of the PKU diet. Parents should be supported
and allowed to express their feelings about the challenges of maintaining their child's restricted diet.
Adolescents with PKU may become fatigued with the constant testing and restrictive diet, so their coping
abilities should be assessed.