Vol. 15 •Issue 1
• Page 39
Type 1 Diabetes In Children and Adolescents
An Overview of Real-Life Issues
By Deborah Lees Holtorf, NP
You send your last patient for lab work and return to your desk. Phone messages and voicemails await attention. The first voicemail is from the school nurse for your patient "Annie." She would like you to discuss several issues with Annie's parents at the child's next clinic visit. "You should see what she brings for snack," she exclaims on the message. "Yesterday, it was a package of chocolate chip cookies! And now they want her to check her blood sugar in the classroom instead of in my office. I just don't think that is safe."
Throughout the United States, providers are struggling to help families make the lifestyle changes necessary to prevent children from developing type 2 diabetes. Annie, however, has type 1 diabetes, diagnosed when she was 18 months old. Now 10 and in fifth grade, Annie is an excellent student and vigorous participant in soccer and gymnastics.
Clinical Background
Diabetes is group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. A number of diabetes types are classified within this broad definition. Nurse practitioners in primary care are most likely to encounter type 1, type 2 and gestational diabetes but should be alert to the variety of endocrinopathies, genetic syndromes and diseases of the exocrine pancreas that may cause or confer a higher risk of diabetes. Type 2 diabetes accounts for 90% to 95% of all diabetes worldwide. Type 1 diabetes comprises 5% to 10% of all diabetes and is still the most common form of diabetes in children and adolescents.1
Type 1 diabetes is characterized by autoimmune destruction of the insulin producing beta cells of the pancreas leading to absolute insulin deficiency. The presence of one or more autoimmune antibodies, including islet cell antibodies, insulin antibodies, autoantibodies to glutamic acid decarboxylase, and autoantibodies to tyrosine phosphatases IA-2 and IA-2 beta, confirms a diagnosis of type 1 diabetes in 85% to 90% of people with the disease. People with type 1 diabetes are more prone to other autoimmune disorders.1
Etiology and Epidemiology
The incidence of type 1 diabetes in children and adolescents has risen sharply over the last 50 years. While the greatest rise has occurred in children between birth and age 4, the number of children diagnosed between the ages of 5 and 14 has also risen dramatically. Evidence suggests that increasing disease in these age groups reflects a shift in the age of diagnosis rather than an overall increase in the lifetime incidence of type 1 diabetes.2 Genetic susceptibility must be present for type 1 diabetes to develop, but many people who are susceptible do not develop the disease. In an analysis of 228 twin pairs in Finland, the incidence of type 1 diabetes in both twins was 27.3% in monozygotic twin pairs and 3.8% in dizygotic twin pairs. Concordance rose to about 50% when the first twin was diagnosed before age 10.3
Viruses (particularly enteroviruses), childhood immunizations and infant feeding practices have all been anecdotally associated with the onset of type 1 diabetes, but only congenital rubella has been conclusively linked to an increased risk of disease. No association has been found between childhood immunizations and increased risk for type 1 diabetes.4 A relationship between early introduction of cow's milk and type 1 diabetes has been demonstrated in some studies but not in others. The results of a recent study suggest that susceptible infants exposed to cereal before age 4 months or after 7 months may be at greater risk of developing the disease.5
Two broad theories relating to the earlier age of onset of autoimmunity, the accelerator hypothesis and the hygiene hypothesis, provoke lively discussion among diabetes researchers and providers. The accelerator theory notes that the increased incidence of type 1 diabetes in younger children tracks with more rapid growth and increasing overweight in the same population. Simply put, this theory proposes that early rapid growth overtaxes pancreatic beta cells, making them more susceptible to early autoimmune attack.5 The hygiene hypothesis, originally used to explain the rise in asthma and allergy, proposes that the immature immune system requires exposure to a range of pathogens to become fully functional. In developed societies, lack of crowding, infrequent early exposure to farm animals and the widespread use of products such as antibacterial soap limit such exposure.2
Diagnosis
Type 1 diabetes has a broad range of presentations, from the incidental finding of glucosuria at a child's annual exam to coma resulting from diabetic ketoacidosis.
Typically, a child or adolescent is diagnosed with diabetes when parents seek an explanation for the child's polyuria, polydipsia, polyphagia, fatigue and weight loss or slowed growth. Abdominal pain and nausea may be present. Fungal infections, especially vaginal candidiasis in girls, are common at diagnosis.
Diabetes is diagnosed according to American Diabetes Association (ADA) criteria. One of the following must be present:
Symptoms of diabetes and a casual plasma glucose 200 mg/dL or higher. Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia and unexplained weight loss.
Fasting plasma glucose of 126 mg/dL or higher. Fasting is defined as no caloric intake for at least 8 hours.
2-hour plasma glucose of 200 mg/dL or higher during an oral glucose tolerance test. The test should be performed as described by the World Health Organization using a glucose load of 75 grams anhydrous glucose dissolved in water or 1.75 g/kg body weight if weight is less than 40 pounds.1
These criteria do not differentiate among types of diabetes, and the distinction between type 1 and type 2 diabetes cannot always be made at the time of diagnosis. Most prepubertal children of normal weight are assumed to have type 1 diabetes, but overweight adolescents — even those with a positive family history of type 2 diabetes — may have positive antibodies indicating autoimmune disease. In the past, we assumed that patients with type 2 diabetes did not develop ketoacidosis. But it is possible for an adolescent presenting in ketoacidosis to be antibody-negative and able to control his or her diabetes with lifestyle changes and oral diabetes medication once the disease is stabilized. All children and adolescents who present acutely with diabetes are initially managed with insulin.
About 25% of infants and children in the United States are in diabetic ketoacidosis (DKA) at the time of diagnosis. DKA is a medical emergency with a mortality rate varying from 0.15% to 0.3%. DKA is defined by a blood bicarbonate less than 15 mmol/L or pH less than 7.25 (7.3 if arterial or capillary). Death from DKA can be attributed to a number of causes but most frequently is a result of cerebral edema, which is more common in young children.6
Insulin
Until 1922, when Frederick Banting, MD, and colleagues successfully used insulin derived from ox pancreas to treat diabetes in a human, a diagnosis of type 1 diabetes predicted sure death. Today, a variety of human insulins and analogs are available, and early death from diabetes is rare.
A child or adolescent with a new diagnosis of type 1 diabetes is immediately treated with insulin. A child in DKA receives insulin by intravenous drip until stabilized. The child who is not acutely ill at diagnosis can be managed with subcutaneous insulin. Initial dosage is approximately 0.5 to 1.0 unit per kilogram of body weight per day.
Traditionally, the total insulin dose was divided into two to three daily injections using a combination of rapid-acting and intermediate- or long-acting insulin. More recently, long-acting "peakless" basal insulins, such as glargine (Lantus) and detemir (Levemir), may be used in combination with rapid-acting insulin. These basal-bolus insulin programs give about half the total daily dose as basal insulin and the other half as boluses of rapid-acting insulin intended to cover carbohydrate and correct hyperglycemia as needed. Available rapid-acting insulins are insulin aspart (Novolog), insulin glulisine (Apidra) and insulin lispro (Humalog).
Caregivers must calculate bolus insulin using ratios that are individualized for the child. The insulin-to-carbohydrate ratio is the number of grams of carbohydrate covered by a single unit of rapid-acting insulin. The correction or sensitivity factor is the reduction in blood sugar produced by a unit of rapid-acting insulin expressed in milligrams per deciliter. A target blood sugar is assigned so that a correction dose can be calculated by subtracting target blood sugar from actual blood sugar and dividing it by the correction factor. The resulting number represents the units of rapid-acting insulin required to bring blood sugar to target.
The same logic is programmed into newer insulin pumps. Insulin pumps use only rapid-acting insulin delivered through a subcutaneously inserted cannula. A portion of this insulin is given slowly and continuously to provide for basal need, and a portion is delivered as programmed by the pump wearer or caretaker when carbohydrate coverage or a blood glucose correction is required.
In theory, the child or adolescent who is receiving insulin according to a basal-bolus plan can eat as frequently and as much carbohydrate as a peer without diabetes. If he or she is not using a pump, however, each meal or snack containing carbohydrate will require an additional small injection.
Type 1 Diabetes Management
The ADA recommends that, when possible, all children with new-onset diabetes be evaluated by a team that consists of a pediatric endocrinologist, a nurse educator, a dietitian and a mental health provider.7 The pediatric diabetes team recognizes that children with diabetes are not just small adults. Parents who have diabetes quickly recognize the increased complexity of managing their child's disease.
There are advantages to being able to hospitalize newly diagnosed children, even those who are not acutely ill at presentation. A short stay in the hospital provides an opportunity for families to begin to work through a wide array of emotional responses while learning the basic survival skills necessary for diabetes management. Blood glucose monitoring, insulin injection technique and basic meal planning or carbohydrate counting can be systematically taught in a safe, supervised setting. An outpatient pediatric diabetes clinic that has flexible availability to work intensively with families during the immediate post-diagnosis period offers similar advantages.
Caregivers should be able to communicate with the child's diabetes providers on a daily basis if necessary during the first several weeks after diagnosis. Pancreatic beta cells not already destroyed by the autoimmune process at the time of diagnosis may regain function, resulting in a temporary remission. Insulin needs may decrease rapidly during this phase and then increase again when the remaining beta cells are destroyed.
Perhaps the most important influence on current diabetes management, the Diabetes Control and Complications Trial (DCCT) followed more than 1,400 volunteers with type 1 diabetes in 29 medical centers in the United States and Canada for 6.5 years. The study compared the effects of two treatment approaches, standard management and intensive management, on the development of long-term complications of diabetes. The results showed that lowering blood glucose through intensive management significantly reduced the risk of eye, kidney and nerve disease.8 Because the most significant side effect of intensive diabetes treatment was hypoglycemia, and the youngest participants in the trial were 13 years old, the DCCT researchers did not recommend intensive treatment for children under 13 as a result of the trial.
Since the DCCT, the development of more rapid-acting analog insulins and more widespread use of insulin pump therapy have increased the safety of intensive management in young children as well as adolescents. Using insulin lispro, researchers lowered hemoglobin A1c (a measure of average blood glucose over the most recent 2 to 3 months) in children without increasing the incidence of severe hypoglycemia.9 The use of insulin pumps has also been associated with decreased risk of severe hypoglycemia.10
The ADA recommendation for glycemic control in children and adolescents takes into account hypoglycemia risk, relatively low risk of diabetes complications before puberty, and developmental and psychological issues common in children and adolescents. In its position statement, the ADA notes that goals should be individualized and that lower goals may be reasonable based on benefit-risk assessment.7 The ADA recommendations are outlined in the table accompanying this article.
Glycemic control is regularly assessed by monitoring patterns in blood glucose readings and the measurement of A1c. Children with type 1 diabetes should also be screened for microalbuminuria, hypertension, dyslipidemia, retinopathy and associated autoimmune conditions including thyroid disease and celiac disease. Guidelines for these screenings are provided within the ADA recommendations for children and adolescents.7
Achieving recommended glycemic control is only part of successful diabetes management in children and adolescents. If blood glucose levels are maintained in target range at the expense of the child's timely achievement of normal developmental milestones, one set of risks has been traded for another. Diabetes management is complex and constant. Even among capable and well informed children, the multifaceted work of managing diabetes exceeds developmental capacity until late adolescence. The young person who willingly and ably takes over blood glucose checking and insulin administration often tires of the unrelenting nature of these tasks. Handing this work back to an adult caregiver, however, may be perceived as failure by children and caregivers alike.
Managing diabetes successfully through the adolescent years is particularly tricky. Normal development requires that the adolescent seek increased freedom from adult supervision. Equally a part of normal development is the adolescent's inability to relate current action to future conditions. Infrequent blood sugar monitoring and insulin omission may signal "diabetes burnout" or deeper depression. Young people with diabetes may self-report depressive symptoms meeting the clinical cut-off for clinical depression at about twice the rate predicted for young people in general.11 Purposeful insulin omission by adolescents, usually girls, to control weight is a particularly dangerous behavior and should be considered whenever a young person with diabetes presents with rapid weight loss and a high A1c level.
Quality of Life
In addition to dedicated families, an involved diabetes team and alert primary care providers, community resources are needed to shape an environment within which the child with diabetes can flourish. Since most children spend much of their time in school, a well-informed school nurse can be a strong ally.
Children with diabetes are protected from discrimination under the Americans with Disabilities Act. In addition to a medical management plan, a 504 plan should be in place that includes diabetes education for all involved school personnel, permission to treat hypoglycemia wherever and whenever it occurs, access to insulin as needed, unfettered bathroom and drinking water access, blood glucose parameters for academic testing, and excused absence for diabetes-related illness and medical appointments. Students with diabetes must be able to safely participate in gym, school sports and other school activities. The school must make provisions for the student with diabetes to go on class field trips whether or not his or her parent attends. A sample 504 plan is available on the ADA Web site at www.diabetes.org.
Participation in sports and other physically strenuous activities should not be limited by type 1 diabetes. Physical activity increases sensitivity to insulin and, with appropriate planning, can improve glycemic control.
Many children with type 1 diabetes find blood glucose checks the most difficult part of diabetes management. Recently, two subcutaneously inserted sensors that allow the wearer to track trends in blood glucose levels have been approved by the FDA for patients 18 and older (the DexCom STS by Dexcom Inc. and the Guardian RT by Medtronic). These sensors typically remain in place for 3 days and must be regularly calibrated with a conventional glucometer. Neither sensor communicates directly with the dosing software of an insulin pump, but data from the Guardian RT can be transmitted to Medtronic's newest insulin pumps. These new tools for continuous glucose monitoring are causing considerable excitement within the diabetes community because they represent a step toward the availability of a "smart pump" that may someday respond to blood glucose levels automatically.
Putting It Into Practice
It is now time to return to the response to Annie's school nurse. As long as cookies fit into Annie's meal plan or can be covered by a bolus of insulin, she is allowed to eat them. If the school has healthy snack guidelines for all children, Annie can be asked to follow them unless she is treating low blood sugar. With regard to checking blood glucose in the classroom, if Annie is capable of performing her own checks safely and is willing to do so in the classroom, she should not be required to miss academic or social time to go to the nurse's office. To make the nurse and school staff feel more at ease, written protocols should be available for the treatment of hypoglycemia and for use of the pump to correct hyperglycemia or cover carbohydrate. These actions can be verified by a trained adult in Annie's classroom.
As long as Annie, her family and others who are involved in her care are well-informed and willing to work together, the only obvious indication that Annie has type 1 diabetes will be the insulin pump clipped to her belt.
References
1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29(suppl 1):S43-S48.
2. Gale EA. The rise of childhood type 1 diabetes in the 20th century. Diabetes. 2002;51(12):3353-3361.
3. Hyttinen V, et al. Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes. 2003;52(4):1052-1055.
4. Graves PM, et al. Lack of association between early childhood immunizations and beta cell autoimmunity. Diabetes Care. 1999;22(10):1694-1697.
5. Devendra D, et al. Type 1 diabetes: recent developments. BMJ. 2004;328(7442):750-754.
6. Wolfsdorf J, et al. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159.
7. Silverstein J, et al. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186-212.
8. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329(14):977-986.
9. Chase HP, et al. The impact of the Diabetes Control and Complications Trial and Humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes. Diabetes Care. 2001;24(3):430-434.
10. Plotnick L, et al. Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. Diabetes Care. 2003;26(4):1142-1146.
11. Hood KK, et al. Depressive symptoms in children and adolescents with type 1 diabetes: association with diabetes-specific characteristics. Diabetes Care. 2006;29(6):1389-1391.
Deborah Lees Holtorf is a pediatric nurse practitioner who practices in the pediatric and adolescent unit at the Joslin Clinic in Boston. In addition to a master's degree in nursing, she has a master's degree in public health.
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