Caring for Children with Diabetes

US Pharm. 2006;31(11)(Diabetes suppl):21-30.

Children have historically been heavily impacted by diabetes. In the early decades of the last century, before diabetes was recognized as being not one but many distinct endocrine disorders, children were among the most frequently diagnosed with those disease. Terms such as juvenile diabetes and childhood-onset diabetes were used to describe what is now known as type 1 diabetes mellitus (DM). More recently, the number of children diagnosed with type 2 DM, a disease formerly thought to be exclusive to adults, has exploded. Diabetes is one of the most frequently diagnosed chronic diseases in children, with more than 175,000 persons in the United States younger than 20 years having some form of diabetes.¹

Pharmacists have always been integrally involved in the care of children with diabetes. For example, when the Durham-Humphrey Amendment, enacted in 1951, defined the medications requiring a physician's prescription, insulins were specifically excluded in order to allow pharmacists to dispense these live-preserving treatments without prior authorization. More recently, the Asheville Project diabetes program, clinics that have pharmacotherapists on staff, and community pharmacyñbased diabetes self-education classes highlight the continuing role of pharmacists in caring for patients with diabetes. This review familiarizes pharmacists with the many aspects of diabetes care relevant to children and adolescents living with diseases in this family.

Type 1 DM in Children
Type 1 DM, or insulin-dependent DM, is an autoimmune disease involving pancreatic beta-cell destruction and resultant insulin-production deficiency. This disease accounts for approximately 5% to 10% of all cases of diabetes.In the U.S., its average age of onset is 14 years.² The rate of beta-cell destruction is variable but appears to be faster in young children than in older patients. As a result, ketoacidosis is more likely to be the presenting problem among children and adolescents at time of diagnosis than it is among adults.³

Type 1 DM is treated with multiple daily insulin injections (either three or four times a day) or with basal/bolus insulin infusion devices (insulin pumps).³ Due to the complexity of the interactions between glucose and insulin, meals, and exercise, children with type 1 DM must test their blood glucose levels very frequently. Even small changes in any of these factors can have a dramatic impact on blood glucose, resulting in dangerously high or low levels. Children should be counseled to check their blood glucose as directed by their clinician and to pay special attention to readings taken when their daily routine is changed. They should never miss meals or insulin doses, and they should monitor blood glucose levels before and after exercise. Those with a history of exercise-induced hypoglycemia or those participating in endurance events should be counseled to check their glucose levels during exercise.

A less common variant of type 1 DM, idiopathic type 1 (or Flatbush) DM is diagnosed most often in young African-American or Asian men. It is similar to autoimmune type 1 DM in its clinical presentation but differs in that it is not associated with detectable beta-cellñdestroying antibodies.² The main clinical difference between autoimmune type 1 DM and idiopathic type 1 DM is that those with the idiopathic variant may have waxing and waning insulin production for years after diagnosis, and as a result, frequent insulin dose adjustments are needed.

Insulin Pump Therapy for Type 1 DM:Insulin delivered continuously through an insulin pump is an extremely successful strategy for intensive diabetes management and is gaining widespread acceptance in the U.S. Insulin pump therapy simulates the function of beta-cells more closely than do multiple daily injections.³ An insulin pump delivers a constant basal insulin infusion and has the ability to deliver larger insulin boluses around mealtimes. The bolus rate and size can be altered depending upon caloric intake, expected activities, and other situations (e.g., illness, emotional trauma) that can impact insulin demands. The many advantages of insulin pump therapy include better insulin pharmacokinetics, individualization of insulin therapy, and greater freedom in timing of meals. The use of insulin pump therapy requires great motivation for frequent blood glucose monitoring, carbohydrate counting, and regular medical visits. The use of insulin pump therapy among children with type 1 DM is predicted to increase along with expanded insurance coverage.

Type 2 DM in Children
Once thought of as adult-onset DM, type 2 DM is becoming more common in children and adolescents; however, the significance of this increasing prevalence may be underestimated, as the disease may be difficult to diagnose or confused with other types of diabetes in children.⁴ The increase in type 2 DM in children parallels the continued increase in overweight and obesity in the U.S. In late 1970s, about 4% of children were overweight, compared to more than 17% of children in 2004, with Mexican-American boys and girls and African-American girls at greatest risk for overweight.⁵

Diagnosing type 2 DM is difficult, since children are often asymptomatic or unaware of their symptoms. Clinicians must rely on family history and physical parameters to consider testing for type 2 DM and laboratory information for the diagnosis.⁴ Criteria for testing children and adolescents for type 2 DM are described in Table 1.

Correctly classifying a child's diabetes type is critical to initiating appropriate treatment. The predominant dysfunction in type 2 DM is insulin resistance.⁴ Therefore, medications that increase insulin sensitivity are most useful for the treatment of this disease.

Lifestyle modification with dietary intervention and physical activity are the primary management strategies of type 2 DM in children. Depending on the severity of disease, metformin (FDA approved for children 10 years and older) and/or insulin (at bedtime, twice a day, or multidose regimens) may be the initial drug treatment(s) in children with type 2 DM. For example, a child with symptomatic, severe disease may begin insulin for most effective diabetes control, followed by a titration to an oral medication. Conversely, a child with asymptomatic but uncontrolled diabetes may use metformin initially. The benefits of metformin over other oral agents for treatment of diabetes are a decreased risk of hypoglycemia and possible weight and cholesterol reduction. Clinical trials are evaluating thiazolidinediones in children; these agents may eventually gain a role in the management of type 2 DM in children.⁶

Diabetes Complications and Concurrent Diseases

Many children and adolescents with diabetes may have microvascular complications and/or cardiovascular disease (CVD) risk factors. Control of weight, glucose, lipids, and blood pressure in children is necessary to prevent or delay development of complications and diseases.⁴ Common medications used to treat diabetes and associated diseases in children are listed in Table 2.

Diabetic retinopathy is damage to blood vessels in the retina that eventually leads to vision loss and blindness. Retinopathy may occur in both types of diabetes, although it is found more frequently in children with type 1 DM than in those with type 2 DM. ⁷ Children with good glycemic control can be screened for retinopathy every two years beginning at age 10 years and once the child has had type 1 DM for three to five years. Adolescents with poor glycemic control, diabetes for more than 10 years, or diagnosed retinopathy need more frequent screening. ⁸

Diabetic nephropathy is the most common cause of chronic kidney disease in the U.S. Nephropathy may occur more frequently in children with type 2 DM than in those with type 1 DM.⁷ Screening for microalbuminuria is recommended annually for both types of diabetes beginning at the time of diagnosis of type 2 DM and beginning at age 10 years and once the child has had type 1 DM for five years.⁹ Screening should begin earlier (one year after diagnosis) for type 1 DM diagnosed during adolescence, since puberty is an independent risk factor for microalbuminuria.⁹ Confirmed elevated microalbumin levels may be treated with angio!= tensin-converting enzyme inhibitors (ACE-Is), although extreme caution is necessary when these agents are prescribed for sexually active female adolescents due to the risk of fetal abnormalities.

Peripheral and autonomic neuropathy caused by nerve damage occur at similar rates in children with type 1 or type 2 DM.⁷ Annual foot examinations should begin at puberty. ⁴

CVD risk factors are prevalent in both types of diabetes, although a large waist circumference, hypertension and high triglyceride and low HDL-cholesterol levels (National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria) occur at least three times more frequently in children and adolescents with type 2 DM.¹⁰ Abdominal obesity and/or overweight may directly impact the development of type 2 DM, hypertension, and dyslipidemia.⁴ The clinical and laboratory parameters for CVD risk factors are found in Table 3.

Dietary intervention and physical activity, possibly along with pharmacologic therapy, are necessary to prevent or delay the development of and to treat CVD risk factors.¹¹ ACE-Is (or approved angiotensin II receptor blockers [ARBs]) are considered first-line agents for treatment of hypertension in children with diabetes. ¹² Pharmacologic treatment for prehypertension should be initiated if goal blood pressure is not attained after three to six months of lifestyle modifications.¹² A fasting lipid panel should be obtained at diagnosis once glucose control is established and followed every two years for type 2 DM and every five years for type 1 DM if LDL† cholesterol remains at or below 100 mg/dL.¹³

Management with statins is indicated in children 10 years and older who are not at goal after six months of lifestyle modification and have an LDL cholesterol level of at least 160 mg/dL, or 130 to 160 mg/dL with other CVD risk factors.¹³ Again, fetal abnormalities may occur if statins are used in sexually active female adolescents who become pregnant; thus, contraception is mandatory.

Emotional Impact of Diabetes

Regardless of age, children diagnosed with diabetes often face tremendous emotional stress. Many of these negative emotional effects are amplified in children and adolescents. They may think themselves to be markedly different from their peers, a situation that can lead to self-doubt and self-imposed isolation. It has been shown that children with diabetes have a twofold increase in rates of depression, and adolescents have a threefold increase, compared to those without diabetes. ¹⁴ Children with concurrent diabetes and depression have a tenfold increase in suicide and suicidal ideation.¹⁴

Typically, a child diagnosed with diabetes will report mild depression and anxiety immediately following diagnosis, with resolution of these complaints six to 12 months later. These depressive symptoms often return in one to two years. While boys usually lose anxiety symptoms during the six years following diagnosis, girls often demonstrate an increase in anxiety.³

Aside from the overall negative impact of depression upon youth, depression negatively impacts diabetes control. One recent study found that adolescents ages 13 to 18 with psychiatric comorbidities had a significantly higher rate of diabetes-related hospitalization than did those without.¹⁵ Interestingly, this difference was not significant among younger children, which points toward the greater impact of mood disorders among adolescents.

An important consideration when treating a child with diabetes is appropriate self-management by age. ³ As children develop, it is important to allow them to accept more responsibility for their own nutritional intake, monitoring, and treatment. A child who is never allowed to care for himself or herself will not develop the skills needed to cope with this lifelong disease. The pharmacist can aid in the transition of care by always including the child and parent in educational sessions.

Another troubling trend has been that children entering adolescence while undergoing insulin therapy often have body-image issues due to the adipose-forming effects of exogenous insulin. As a result, some adolescents decrease or eliminate insulin therapy in order to lose weight. The resultant acidosis can lead to rapid and profound weight loss, further encouraging this dangerous activity, in the mind of the patient. Pharmacists should pay close attention to adherence to insulin therapy and should take notice of sudden or unexplained weight loss during the adolescent and college years.

In addition to considering the impact of diabetes on the mental health of the child, pharmacists should be conscious of the emotional well-being of the parents or caregivers. For instance, caring for an infant with diabetes dramatically increases the already significant emotional toll on the parents.¹⁶ The complexity of diabetes management plans and concerns of hypoglycemia may be overwhelming. Pharmacists must take the time to question parents about their emotional and mental health and refer for appropriate therapy as needed.

Pharmacist Involvement with Diabetes

By increasing their involvement in caring for children with diabetes, pharmacists affirm their role as health care leaders in the community. For instance, most regions of the country have "diabetes camps," which provide a traditional camping experience to children and adolescents with diabetes, in a medically supervised environment. These camps enroll 15,000 to 20,000 children each year and can always use the expertise of a pharmacist for dispensing medications and counseling the children on their disease and its treatments.¹⁶ The Clinical Practice Guidelines of the American Diabetes Association (ADA), published every January in Diabetes Care, include guidelines for appropriate management of these camps.¹⁷

These guidelines also include recommendations for schools and daycare centers that enroll children with diabetes.¹⁸ For instance, these institutions should design individualized management plans that detail when a student may check his or her glucose or administer medication and which activities the child may participate in. Pharmacists can help ensure that school boards and administrators adhere to these recommendations. The clinical practice recommendations are available on the ADA Web site (www.diabetes.org).

Another valuable resource for children with diabetes and their caregivers is the Children with Diabetes Web site (www.childrenwithdiabetes.com). This site offers family support networks, a question-and-answer forum, and recommendations for improving the quality of life of a child with diabetes. Although this site does accept advertising, its content is largely without commercial bias or influence, setting it apart from many "informational" sites operated by pharmaceutical or monitoring device manufacturers. One interesting component of this site is a set of formal guidelines for babysitters of children with diabetes. Included are recommendations (e.g., when and what to feed the child, when to give medications, when to contact the parents) that should increase the comfort level of both the parents and the babysitter.

Conclusion
Pharmacists have ample opportunity to expand their role in the management of children and adolescents with both type 1 and type 2 DM. A greater understanding of diabetes and its complications along with associated CVD risk factors allows pharmacists to become more proactive in screening, recommending and monitoring pharmacologic therapy, and counseling children and adolescents with either type 1 or type 2 DM. Pharmacists must also understand the emotional toll of diabetes and be cognizant of the risk of depression in children and their caregivers. Children with diabetes must be treated as much as possible like children who do not have the disease in order to minimize the impact of diabetes upon their quality of life. Beyond these standard components of practice, pharmacists must also consider increasing their role in improving community standards for the care of children living with diabetes.

References

1. American Diabetes Association. Standards of medical care in diabetes (Position Statement). Diabetes Care .2006;29:S4-S42.

2. American Diabetes Association. Diagnosis and classification of diabetes (Position Statement). Diabetes Care .2006;29:S43-S48.

3. American Diabetes Association. Care of children and adolescents with type 1 diabetes (Statement). Diabetes Care. 2005;28:186-212.

4. American Diabetes Association. Type 2 diabetes in children and adolescents (Consensus Statement). Diabetes Care.2000;23:381-389.

5. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295:1549-1555.

6. National Institute of Diabetes and Digestive and Kidney Diseases. Treatment options for type 2 diabetes in adolescents and youth (TODAY). Available from: www.todaystudy.org/medp1.cgi. Accessed March 30, 2005.

7. Eppens MC, Craig ME, Cusumano J, et al. Prevalence of diabetes complications in adolescents with type 2 compared to type 1 diabetes. Diabetes Care. 2006;29:1300-1306.

8. Maguire A, Chan A, Cusumano J, et al. The case for biennial retinopathy screening in children and adolescent. Diabetes Care. 2005;28:509-513.

9. Gross JL, DeAzevedo MJ, Silveiro AP. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2005;28:164-176.

10. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ. Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes. Diabetes Care. 2006;29:1891-1896.

11. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

12. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114:555-575.

13. American Diabetes Association. Management of dyslipidemia in children and adolescents with diabetes (Consensus Statement). Diabetes Care. 2003;26:2194-2197.

14. Grey M, Whittemore R, Tamborlane W. Depression in type 1 diabetes in children; natural history and correlates. J Psychosom Res. 2002;53:907-911.

15. Garrison MM, Katon WJ, Richardson LP. The impact of psychiatric comorbidities on readmissions for diabetes in youth. Diabetes Care. 2005;28:2150-2154.

16. Banion CR, Miles MS, Carter MC. Problems of mothers in management of children with diabetes. Diabetes Care . 1983;6:548-551.

17. Diabetes care at diabetes camps. Diabetes Care. 2006;29:S56-S68.

18. Diabetes care in the school and day care setting. Diabetes Care. 2006;29:S49-S55.

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