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of rapid acting insulin or the insulin sensitivity. For example, a child on 32 U of insulin per day would have an insulin sensitivity of 1600/32 or 50. We would then advise that the child receive an additional 1 U of rapid-acting insulin for every 50 mg/dL glucose above the defined target (typically >120 mg/dL over age 8 years).

Glargine and continuous subcutaneous insulin infusion

Basal-bolus insulin usage that employs glargine insulin and rapid-acting analogs and CSII has increased. Glargine and continuous subcutaneous insulin infusion (CSII) are most often offered to children who already have demonstrated the ability to manage their diabetes somewhat independently and to preschool-aged children who have committed parents. In families with previous diabetes knowledge, insulin glargine or CSII should be considered at diagnosis. Several studies have demonstrated the ability of CSII and insulin glargine to improve metabolic control and hypoglycemia frequency in young children and toddlers. Although CSII and glargine regimens require more frequent blood glucose testing and insulin administration than fixed doses, many children and parents accept the increased work required because of the lifestyle flexibility afforded by this schedule. Despite these advantages, overall glycemic control may not improve just because a child is switched to CSII or glargine. All regimens will fail unless a child and family are committed to performing the diabetes tasks necessary to succeed. Before changing therapy, we require children interested in using glargine or CSII to attend a carbohydrate counting and pump class, monitor their blood glucose a minimum of four to six times per day, call weekly with blood glucose results, and record carbohydrate intake and insulin boluses based on a prescribed insulin-to-carbohydrate ratio and correction factors.

Initial glargine doses are typically calculated by using 60% to 70% of the total intermediate-acting insulin previously given. For initial pump rates, most children use 70% to 80% of their previous total daily amount of subcutaneous insulin, with 60% of their previous intermediate-acting insulin dose given as a basal dose divided over 24 hours. Meal coverage is determined by using insulin-to-carbohydrate ratios. Ratios in children tend to be anywhere from 1:30 for young children to 1:5 for adolescents at the peak of insulin resistance. Supplemental insulin calculated as correction factors before beginning CSII or insulin glargine therapy should continue to be used (see the article by Weinzimer and colleagues elsewhere in this issue— on insulin pump therapy).

Potential adjuncts to insulin therapy

Despite the development of long- and rapid-acting insulin analogs, subcutaneous insulin administration is still unable to match normal insulin secretion perfectly. Additional therapies are needed to provide patients who have T1D with maximal glucose control. The potential role of glucagon-like peptide-1 analogs, which have shown promise as adjunct therapy for type 2 diabetes in augmenting insulin response, and amylin, a hormone that is normally co-secreted with insulin and may dampen glucagon secretion, are currently being explored as potential therapies in patients who have T1D [81,82].

Self blood glucose monitoring

Self blood glucose monitoring is the cornerstone of diabetes management. Intensive diabetes management mandates that patients perform frequent self blood glucose monitoring at least four to six times a day. Frequent self blood glucose monitoring empowers patients and their families and enhances the understanding of insulin, food, and exercise effects on blood glucose. It also affords multiple opportunities to provide additional insulin to correct hyperglycemia and improve control. Regardless of the insulin regimen being prescribed, frequency of self blood glucose monitoring correlates directly with improved glucose control [83]. Because the Diabetes Control and Complications Trial demonstrated the importance of maintaining tight glycemic control on minimizing microvas-cular disease, intensive diabetes management is the standard of care. The inconvenience, cost, and pain of self blood glucose monitoring may limit its use for some patients.

In addition to finger tip glucose monitoring, continuous glucose monitoring systems may allow for more intensive self blood glucose monitoring. Current continuous glucose monitoring systems use a subcutaneous catheter that transmits data on interstitial fluid glucose to a transmitter that is worn much like an insulin pump. After 3 days, the transmitter is downloaded and the data can be reviewed retrospectively. Real-time continuous glucose monitoring systems, which would provide readings on a digital screen every 5 minutes, are expected to be available in the near future [84].

Medical nutritional therapy

Perhaps the most important—yet often neglected—part of diabetes management is medical nutritional therapy. Although physicians often focus on insulin dosing and self blood glucose monitoring, optimal management requires proper recognition of the balance among insulin, exercise, and food. All families with a newly diagnosed child should receive consultation with a nutritionist, and most children and their families should be given a refresher course annually. Because the obesity epidemic has not spared the T1D population, increasing efforts must be made to encourage physical activity and limitation of excess caloric intake. Specifically, children should be encouraged to perform 30 to 60 minutes of exercise at least five times per week. Caloric intake should include approximately 50% to 55% of calories from carbohydrates, 15% to 20% from protein, and 30% from fat. The American Diabetes Association no longer recommends a specific diet and advises that individualized adjustments be made depending on activity and other metabolic demands.

With the increasing popularity of CSII and glargine insulin regimens, children who have diabetes must have an adequate understanding of how carbohydrates, protein, and fat affect blood glucose. Detailed carbohydrate counting instruction should be a cornerstone of diabetes education for all children who have diabetes, especially children who use CSII or glargine. When children are asked to report their prescribed carbohydrate ratio and correction factor, we should ask them directly to calculate a meal time insulin dose based on a typical meal and their current blood glucose. Using real world examples helps determine if a child or family needs more detailed nutritional education.

Sick day management

When children who have diabetes have an illness, the primary goal is to avoid ketoacidosis. Urine must be checked for ketones frequently. If ketones are present, additional regular insulin should be given and repeated every 4 hours if necessary. For moderate ketone levels, an additional 15% to 20% of the total daily insulin dose should be given; for large ketone levels, 25% to 30% of the total daily insulin dose should be given. When children have an illness that limits their oral intake or have low blood sugars, insulin adjustments can be difficult. For children on standard combinations of NPH and rapid-acting analogs who refuse to eat, small amounts of easily absorbable glucose may be necessary to avoid hypoglycemia. Doses of rapid-acting analogs also can be held until immediately after a child has eaten to determine if and how much of the dose should be given. Children who are not eating well and are on combination therapy with NPH and rapid-acting analogs may need a 25% to 30% reduction in their NPH dose to avoid hypoglycemia. On the other hand, children who use CSII or glargine may require a 10% to 15% increase in basal rates on sick days to avoid lipolysis.

Hypoglycemia

Fear of or actual hypoglycemia is one of the most important factors that limits the implementation of intensive diabetes management. Because even the best diabetes management provides exogenous insulin in a nonphysiologic manner, appropriate management of hypoglycemia must be discussed at initiation of insulin therapy and should be reviewed at each clinic visit. For the initial treatment of hypoglycemia in a responsive child, 15 g of rapid acting carbohydrate (eg, 4 oz juice, three glucose tablets) should be given, which should raise the blood glucose level 15 to 20 mg/dL after 10 minutes. Families also must be taught how to mix and administer glucagon (0.5-1 mg intramuscularly) in case a child is unconscious or seizing or does not respond to oral glucose.

Avoidance of severe hypoglycemia is critical in young children because of concerns over damaging active brain development. Children who are tightly controlled and experience a severe hypoglycemic event often have markedly higher HbA1c for several years. This occurs because parents of children who have experienced a severe hypoglycemic event often develop a significant fear of hypoglycemia and respond by withholding appropriate insulin or overfeeding. To avoid severe hypoglycemia, we advise patients to reduce insulin doses when they experience three or more blood glucose levels less than 60 mg/dL at the same time of day in 1 week, two or more blood glucose levels less than 50 mg/dL at the same time of day in 1 week, or any one blood glucose level less than 40 mg/dL. We also advise our patients that HbA1c goals must be adjusted for age. For further information, please see the article by Becker and Ryan elsewhere in this issue.

Age-specific goals

The risks of severe hypoglycemia must be balanced with the long-term risk of microvascular and macrovascular complications. In children, HbA1c goals must be age adjusted to minimize the frequency of serious hypoglycemia. Unlike adults, children who experience recurrent hypoglycemia at an early age (< 5 years) may be at increased risk for long-term neuropsychological impairment. Premeal glycemic goals for toddlers and preschoolers should be 100 to 180 mg/dL, overnight levels should be 110 to 200 mg/dL, and the HbA1c goal should be between 7.5% and 8.5%. School-aged children (6-12 years) should begin to tighten their control with premeal glucose levels of 90 to 180 mg/dL, overnight levels more than 100 mg/dL, and HbA1c < 8%. In adolescents, the issues of adolescent rebellion and independence require a somewhat more individualized approach. Once a child is in the teenage years, premeal blood glucose levels should be 80 to 120 mg/dL and their lifetime goal should be to maintain HbA1c < 7%. This goal is difficult for most teens to achieve, however, and the American Diabetes Association has recommended an HbA1c goal of 7.5% for this age group, with an ideal HbA1c of < 7% if achievable without hypoglycemia. It is imperative that each child have realistic individualized goals. Encouraging independence, avoiding major parent-child conflict, focusing on small successes, and trying to minimize the psychological impact of diabetes may require goals to be adjusted temporarily.

School issues

Most children spend most of their day in school. Schools must be equipped to deal with children who have diabetes. The overall goal for schools that have children who have diabetes should be to maintain excellent diabetes care while minimizing interruptions to the learning environment. Children must be allowed to check blood glucose levels, give supervised insulin injections, and treat hypo-glycemia in close proximity to the classroom. It is preferable to have a school nurse familiar with diabetes management to oversee a child's diabetes management. Many schools do not have a nurse, however, or if they do, he or she may not be comfortable with diabetes management. When a school nurse is not available, specific training must be provided to a specified diabetes liaison.

Teachers also should be aware of the symptoms and treatment of hypoglycemia, and fast-acting carbohydrates (eg, juice or instant glucose) should be available in all classroom settings. A glucagon emergency kit should be kept in the nurse's station. A child's parent is responsible for providing all diabetes supplies.

In most schools, children must go to the school nurse's station to check blood sugars, give insulin, and treat hypoglycemia. In these situations, children should be accompanied by an aide or a classmate if there is a considerable distance between the classroom and the nurse's station. School nurses or the diabetes liaison also should be provided with specific protocols for treating hypoglyce-mia, checking for ketones, and giving insulin. The health care team is responsible for providing the school personnel with an individual diabetes management care plan.

Giving insulin at school can be a complex problem. When children are on a combination of NPH and rapid-acting analogs, insulin injections at school are not typically required. With the increasing number of children using CSII and glargine insulin, however, school nurses are often responsible for overseeing lunchtime insulin injections. Parents and physicians must be sure that nurses or diabetes liaisons are aware of a child's specific blood glucose goals and are appropriately trained either to give or oversee insulin injections. Frequent communication between school nurses and a child's diabetes care team is important to adjust insulin doses continuously and promote age-appropriate HbA1c goals.

Finally, physical fitness is important for maintaining cardiovascular health and improving metabolic control. Managing children who have diabetes during physical education can be a challenge. Coaches should be trained to allow children who have diabetes appropriate access to fluids and carbohydrates. If physical education is expected to last more than 30 minutes, a 10% to 20% reduction in the insulin dose or a juice box or small snack can be used to avoid hypoglycemia. Glucose testing also should be made available at the site and should be allowed any time a child feels hypoglycemic. The symptoms of physical exertion are often difficult to distinguish from those of hypoglycemia. Full participation in physical education should be expected. Creating an exercise program for children who have diabetes that provides for appropriate monitoring with expectation of full participation is important for teaching children that diabetes should not exclude them from any activities.

Complications

Complications of T1D include retinopathy, nephropathy, neuropathy, and cardiovascular disease. The Diabetes Control and Complications Trial demonstrated the importance of tight glucose control in minimizing these complications. Because most complications from T1D do not present until 10 to 15 years after diagnosis, however, children often underestimate the importance of glycemic control. Because glucose control is linked directly to complication rates, screening for diabetes complications should begin with a HbA1c at every clinic visit. Blood pressure also should be monitored closely and children who have hypertension (blood pressure higher than the ninety-fifth percentile) should be treated aggressively. To screen for neuropathy, a microfilament should be used to check finger and toe sensation at each clinic visit.

Once a child is 10 years old and has had diabetes for 5 years, urine microalbumin should be obtained annually to screen for nephropathy. If the urine albumin/creatinine ratio is more than 30 mg/g, a first morning sample should be obtained to rule out orthostatic proteinuria. If albuminuria persists on more than two to three confirmatory samples, angiotensin-converting enzyme inhibitor therapy should be initiated. Lipid profiles should be obtained on all children once glucose control has been established. If the low density lipoprotein (LDL) is < 100 mg/dL, screening should be repeated once every 5 years. If the LDL is elevated, screening should be repeated annually. Current guidelines recommend pharmacologic treatment for LDL > 160 mg/dL with a goal LDL of < 100 mg/dL. Statins are currently considered first-line therapy for hyperlipidemia [85]. Safety and efficacy have been established in children such that statin therapy can be initiated after 10 years of age [86]. Pharmacologic treatment should be considered in patients who have LDL between 130 and 160 mg/dL with additional cardiovascular risk factors. To screen for retinopathy, a dilated eye examination should be performed by an ophthalmologist annually once a child is 10 years old and has had diabetes for more than 3 years. (See the article by Glastras and colleagues elsewhere in this issue—on screening and management of complications in childhood diabetes.)

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