US Pharm
. 2012;37(5)(Diabetes suppl): 3-6.

Approximately 215,000 people younger than 20 years of age have type 1 or type 2 diabetes.1 Traditionally, it was thought that diabetes in children was always type 1 (formerly known as juvenile diabetes or insulin-dependent diabetes). However, the incidence of type 2 diabetes (formerly known as adult-onset diabetes or noninsulin-dependent diabetes) in adolescents has increased within the last 10 years.2 This is particularly true in minority populations. Type 1 diabetes accounts for 5% to 10% of the population, while type 2 diabetes represents 90% to 95%.2

Definition

Type 1 diabetes is primarily immune mediated and results in autoimmune destruction of the pancreatic beta-cells.3 Beta-cell destruction may be rapid or slow; hence, it may affect patients at different ages. The more rapid the beta-cell destruction, the earlier the onset of type 1 diabetes.3 Patients who exhibit genetic defects of beta-cells may be referred to as having maturity-onset diabetes of youth (MODY). These patients present with an onset of hyperglycemia typically before age 25 years and have no defects in insulin actions; however, they do have impaired insulin secretion. Type 2 diabetes is associated with insulin resistance and relative insulin deficiency.3

Ketoacidosis is a common initial manifestation of type 1 diabetes as well as a likely potential complication throughout life for these patients. Ketoacidosis occurs when insulin is lacking to utilize glucose for fuel and the body resorts to the breakdown of fat for the fuel. Fat breaks down into ketones, resulting in a toxic state that subsequently causes symptoms such as, but not limited to, deep, rapid breathing, dry skin and mouth, flushed face, fruity-smelling breath, nausea and vomiting, and stomach pain.4   Ketoacidosis is uncommon in type 2 diabetes.3

Screening

Diagnosis of diabetes typically occurs shortly after presentation of acute symptoms such as hyperglycemia.2 Type 2 diabetes is far less common in children and adolescents; however, these patients are still at risk for micro- and macrovascular complications.3 The American Diabetes Association (ADA) recommends screening for type 2 diabetes in children and youths. Asymptomatic children and adolescents should be screened for type 2 diabetes if they are overweight (body mass index [BMI] or weight for height >85th percentile for age and sex or weight >120% of ideal for height) and have two of the following risk factors: family history of type 2 diabetes (first- or second-degree relative); race/ethnicity (Native American, African or Asian American, Latino, Pacific Islander); signs of insulin resistance or condition associated with insulin resistance; or maternal history of diabetes or gestational diabetes during the child’s gestation. The ADA recommends that screening begin at 10 years of age or at onset of puberty, whichever is sooner, and occur every 3 years.

Screening for type 1 diabetes is recommended only for high-risk children. This would include children with a history of transient hyperglycemia or who have a relative with type 1 diabetes. Routine screening within the general population is not recommended. Patients may experience an onset of diabetes induced by medications and/or hormones (TABLE 1).3 In addition, certain viruses, including congenital rubella, coxsackie-virus B, cytomegalovirus, adenovirus, and mumps have been associated with the destruction of beta-cells, leading to the onset of diabetes.

Screening and Management of Chronic Complications

Children and adolescents with diabetes can suffer alike from complications such as nephropathy, hypertension, dyslipidemia, retinopathy, celiac disease, and hypothyroidism.2 TABLE 2 provides a summary of recommendations for the screening and management of these complications.

Nephropathy and Hypertension: Screening for nephropathy in children includes a urine dipstick test, which mainly detects albumin in urine.2 This test is sensitive to albumin concentrations as low as 15 mg/dL, corresponding to an albumin excretion of 300 mg/day (with daily urine volume of 2,000 mL). Under normal circumstances, this level gives a trace result with the dipstick test. Anything greater than trace amounts would warrant further testing and treatment.5

Children should be screened for hypertension at least annually. Treatment of high-normal blood pressure (systolic or diastolic blood pressure consistently above the 90th percentile for age, sex, and height)6 includes diet, exercise, and pharmacologic treatment.2 Treatment with ACE inhibitors can be initiated in children who develop microalbuminuria and hypertension. Captopril and enalapril have been used in children as young as 1 month old. Fosinopril, lisinopril, and benazepril should only be used in children >6 years of age.7

Dyslipidemia: Diagnosis of diabetes in childhood can lead to increased cardiovascular risk later in life.8-11 Initial treatment includes medical nutrition therapy (MNT), which has been shown to be safe in children as young as 7 months of age.2,12,13 In addition to MNT, statin therapy is indicated if lipid levels are suboptimal. With the exception of pravastatin (>8 years old), statins are not indicated for children <10 years of age.2-7 Pitavastatin has no dosing recommendation for children.7 Dosing of the various statins is based generally on the lipid-lowering requirements of treatment. Since statins are Pregnancy Category X drugs, postpubertal girls should be educated on exercising proper pregnancy prevention measures.2-7

Diabetic Retinopathy: It most commonly occurs after the onset of puberty and following 5 to 10 years of diabetes, although it has been reported in younger populations.14 The crux of treatment is prevention through glucose control.

Celiac Disease: Patients with type 1 diabetes have an increased incidence of developing celiac disease, an immune-mediated disorder.15,16 Patients with celiac disease often complain of diarrhea, weight loss or difficulty gaining weight, growth failure, gastrointestinal (GI) problems, chronic fatigue, and erratic blood glucose concentrations or hypoglycemia.2 Screening at diagnosis becomes essential in preventing further complications. Treatment involves providing children with a gluten-free diet, including gluten-free medications.2

Hypothyroidism: Up to 30% of patients with type 1 diabetes develop autoimmune thyroid disorders.17 The presence of thyroid autoantibodies is predictive of thyroid dysfunction.18 Thyroid dysfunction can lead to decreased metabolic control and a decrease in growth rate.19,20 Treatment with levothyroxine is age and weight dependent; therefore, dosages should be adjusted based on symptom presentation every 4 to 6 weeks.7

Treatment

The goals of therapy in diabetes management can be achieved with MNT or medications. Treatment should be tailored to achieve the A1C goal and pre- and postprandial targets and to minimize risk of diabetes complications. It is important to note that these targets are age-specific and do not necessarily correspond to adult targets (TABLE 3).

Medical Nutrition Therapy: MNT plays an important in diabetes prevention and self-management. MNT consists of lifestyle and dietary changes that are conducive to achieving weight and glucose control. Lifestyle changes that can be initiated for primary prevention of type 2 diabetes include >7% weight loss, regular physical activity (150/min/week), and a reduction of calorie and fat intake.2 Dietary changes should be enough to meet the metabolic needs of patients, especially in light of increased activity and medications. Strategies to maintain proper caloric intake include carbohydrate counting or experience-based estimations. Additionally, patients should limit their intake of trans fats and saturated fats to <7% to minimize cardiometabolic risk.2

Medical Management of  Type 1 Diabetes: Insulin therapy continues to be the means by which type 1 diabetes is managed. Insulin can be categorized as short-acting (ultra-rapid and rapid-acting insulin) or basal (intermediate and long-acting).

Short-acting insulin is used primarily to control postprandial hyperglycemia. Regular insulin has to be injected 30 minutes before a meal and rapid-acting analogues can be administered either within 15 minutes before a meal or immediately after a meal.21 Due to regular insulin’s relatively longer onset and half-life as compared to ultra-rapid insulin, it is important for children with diabetes to receive proper education on planning meals and developing timely eating habits to avoid hypoglycemia.7 In children who have difficulty planning meals, ultra short-acting insulin provides an alternative for these patients, because of its fast action and flexible mealtime administration. Basal insulin is utilized to mimic the body’s natural basal insulin secretion to limit gluconeogenesis and lipolysis. Neutral protamine Hagedorn (NPH) insulin can be used for basal coverage, although it is technically considered an intermediate-acting insulin. Insulin NPH must be administered at least twice daily to provide such coverage.21

Insulin can be dosed using a basal/bolus method or the insulin to carbohydrate ratio (I:CHO). The basal/bolus method is meant to provide background insulin release to regulate homeostatic glucose concentrations with basal insulin, while also providing postprandial correction for hyperglycemic excursions with a bolus of short-acting insulin.21 The I:CHO is an estimation of the amount of insulin required to meet the expected blood glucose increase that comes with a certain carbohydrate intake.22 An initial food exchange of 1 unit of insulin for every 15 g of carbohydrates can be started and should be adjusted based on physical activity, insulin needs, and glycemic control.22

Medical Management of  Type 2 Diabetes: Treatment of type 2 diabetes in children is targeted at reducing insulin resistance. Methods used include diet, exercise, and medications. Metformin, the only oral agent approved for use in children and adolescents, can be used in children 10 years or older and can be dosed up to a maximum of 2,000 mg/day.7 Extended-release formulations of metformin are generally not indicated in children <17 years old (e.g., Fortamet, Glucophage XR), and some agents have no pediatric indication (e.g., Glumetza). Major precautions for the use of metformin include risk of lactic acidosis under conditions where renal function may be impaired (i.e., IV contrast). Common adverse reactions include GI distress, weight loss, and vitamin B12 deficiency.

Glimepiride (titrated up to 4 mg/day) was compared to metformin (titrated up to 2,000 mg/day) therapy in a study that was comprised mostly of adolescent children (10-18 years).23 There was no difference in efficacy between metformin and glimepiride; however, there was a difference in weight gain.23 Significant differences were observed in mean changes from baseline in BMI between groups (0.26 kg/m2 for glimepiride and -0.33 kg/m2 for metformin; P = .003). The adjusted mean body weight increase was 1.97 kg for glimepiride and 0.55 kg for metformin (P = .005). Glimepiride is currently not indicated for use in children.7

Devices

There are several devices available, including insulin pens, subcutaneous injection ports, insulin pumps, and continuous blood glucose monitors.

Insulin pens are refillable or prefilled penlike injection devices that can provide patients with more precise and accurate insulin administration.24 Both short-acting and basal insulin are available as pen devices. These pens can deliver insulin in 0.5- to 1-unit increments.7 There is also some evidence to show that insulin pens may aid more accurate dosing in children than syringes.25

A subcutaneous injection port is a device that allows a cannula to be inserted subcutaneously for insulin administration. This method of administration may improve adherence and decrease discomfort by reducing the need for repeated skin punctures.

Insulin pumps are also inserted subcutaneously; however, they contain a reservoir filled with insulin for infusion. This method allows for more tailored glycemic control and flexibility.24

The ADA recommends that self-monitoring of blood glucose (SMBG) be performed three or more times daily for patients who are using multiple daily doses of insulin or insulin pump therapy.2 SMBG is also a useful tool to help achieve glycemic control in patients taking other therapies. Glucose meters provide blood glucose control feedback by analyzing small quantities of blood (<1 mcL) sequestered by patients through fingersticks. Most meters are easy to operate and sometimes incentivize children to check blood glucose by offering gift points in exchange for testing.24,26 Continuous blood glucose monitors provide constant feedback on the patient’s blood glucose status. These monitors come equipped with sensors that are inserted subcutaneously, similar to infusion pumps and ports, to measure interstitial plasma glucose.24 The drawback to these monitors is that they sometimes provide inaccurate values due to the slower rate of glucose exchange between the vasculature and interstitial plasma.24 As a result, peripheral samples are still necessary for monitoring. Newer models have the ability to communicate directly with the insulin pump.24 Overall, continuous blood glucose monitors have a role in tracking glucose trends; however, they are not for insulin correction dosing.

Pharmacist’s Role

Literature supports positive outcomes when pharmacists are involved in the care of patients with diabetes, including children and adolescents. Pharmacists in all settings may impact the education of these patients. Diabetes education for parents and child, when applicable, should include insulin injection technique, device use, signs and symptoms of hypo- and hyperglycemia, how to manage disease progression and complications, and goals of therapy.27 Special attention should be paid to circumstances that are unique to children, such as insulin administration and storage at school and hypoglycemic events while playing.28 Pharmacists may advocate for the benefits of day camps for children with diabetes as a viable resource. Pharmacists can play a particular role in the transition from adolescent to adult care.27

REFERENCES

1. National Diabetes Statistics, 2011. National Diabetes Information Clearinghouse. http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.aspx. Accessed February 15, 2012.
2. Standards of medical care in diabetes–2012. Diabetes Care. 2012;35(suppl 1):S11-S63.
3. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35(suppl 11):S64-S71.
4. Diabetic ketoacidosis. PubMed Health. www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001363/. Accessed February 15, 2012.
5. Kallen R. Pediatric proteinuria. Medscape Reference. http://emedicine.medscape.com/article/984289-overview#aw2aab6b3. Accessed February 15, 2012.
6. Rodriguez-Cruz E. Pediatric hypertension. Medscape Reference. http://emedicine.medscape.com/article/889877-overview. Accessed February 15, 2012.
7. Lexi-Comp Online (Lexi-Drugs). www.lexi.com. Hudson, OH: Lexi-Comp, Inc. Accessed February 15, 2012.
8. Krantz JS, Mack WJ, Hodis HN, et al. Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr. 2004;145:452457.
9. Järvisalo MJ, Putto-Laurila A, Jartti L, et al. Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes. 2002;51:493-498.
10. Haller MJ, Samyn M, Nichols WW, et al. Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes Care. 2004;27:2911-2917.
11. Orchard TJ, Forrest KY, Kuller LH, et al. Pittsburgh Epidemiology of Diabetes Complications Study. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care. 2001;24:1053-1059.
12. Salo P, Viikari J, Hämäläinen M, et al. Serum cholesterol ester fatty acids in 7- and 13-month-old children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet: the STRIP baby project. Special Turku coronary Risk factor Intervention Project for children. Acta Paediatr. 1999;88:505-512.
13. The Dietary Intervention Study in Children (DISC). The Writing Group for the DISC Collaborative Research Group. Efficacy and safety of lowering dietary intake of fat and cholesterol in children with elevated low-density lipoprotein cholesterol. JAMA. 1995;273:1429-1435.
14. Cho YH, Craig ME, Hing S, et al. Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006. Pediatr Diabetes. 24 March 2011 [Epub ahead of print].
15. Holmes GK. Screening for coeliac disease in type 1 diabetes. Arch Dis Child. 2002;87:495-498.
16. Rewers M, Liu E, Simmons J, et al. Celiac disease associated with type 1 diabetes mellitus. Endocrinol Metab Clin North Am. 2004;33:197-214.
17. Roldán MB, Alonso M, Barrio R. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Diabetes Nutr Metab. 1999;12:27-31.
18. Kordonouri O, Deiss D, Danne T, et al. Predictivity of thyroid autoantibodies for the development of thyroid disorders in children and adolescents with type 1 diabetes. Diabet Med. 2002;19:518-521.
19. Mohn A, Di Michele S, Di Luzio R, et al. The effect of subclinical hypothyroidism on metabolic control in children and adolescents with type 1 diabetes mellitus. Diabet Med. 2002;19:70-73.
20. Chase HP, Garg SK, Cockerham RS, et al. Thyroid hormone replacement and growth of children with subclinical hypothyroidism and diabetes. Diabet Med. 1990;7:299-303.
21. Schmid H. New options in insulin therapy. J Pediatr (Rio J). 2007;83(suppl 5):S146-S154.
22. Kulkarni K. Carbohydrate counting: a practical meal-planning option for people with diabetes. Clin Diabetes. 2005;23:120-122.
23. Gottshalk M, Danne T, Vlajnic A, et al. Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes. Diabetes Care. 2007;30:790-794.
24. Fowler M. Diabetes devices. Clin Diabetes. 2008;26:130-133.
25. Lteif AN, Schwenk WF. Accuracy of pen injectors versus insulin syringes in children with type 1 diabetes. Diabetes Care. 1999;22:137-140.
26. DIGET blood glucose monitoring system product information. Toronto, Ontario: Bayer Healthcare; March 2012.
27. Shane-McWhorter L. The scope and standards for the practice of diabetes education by pharmacists. American Association of Diabetes Educators. www.diabeteseducator.org/export/sites/aade/_resources/pdf/PharmDScopeStandards.pdf. Accessed February 15, 2012.
28. Role of pharmacists in diabetes management. SS Diabetes Care. www.ssdiacare.com. Accessed February 15, 2012.
29. Comi RJ. Drug-induced diabetes mellitus. In: LeRoith D, Taylor SI, Olefsky JM, eds. Diabetes Mellitus: A Fundamental and Clinical Text. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2004.

To comment on this article, contact rdavidson@uspharmacist.com.