Prospective follow-up of high-risk subjects shows that the diagnosis of type 1 diabetes can be made in most asymptomatic individuals when metabolic abnormalities are still relatively mild.4,5 The progression of T1DM tends to follow a characteristic clinical course that includes an abrupt onset of classical symptoms that rapidly disappear after insulin replacement therapy is begun. A temporary remission (“honeymoon phase”) often follows with partial recovery of endogenous insulin secretion, demonstrable by plasma C-peptide levels and characterized by stable near-to-normal blood glucose levels and decreasing insulin requirements.¹ Severe DKA and young age at presentation reduce the likelihood of a remission phase. Recurrence or persistence of the autoimmune attack on β cells invariably leads to further β cell destruction and progressive decline in insulin production, leading eventually to complete cessation of insulin production in most cases of childhood onset T1DM.

Type 2 Diabetes Mellitus

Numerous recent studies have examined the characteristics at onset of pediatric type 2 diabetes (T2DM) in various populations. A major difficulty in analyzing and interpreting these studies is the wide range of case definitions used to classify youth as having T2DM. Studies that employ strict criteria for the diagnosis of T2DM show several common characteristics, including obesity, a prominent family history of T2DM, acanthosis nigricans, female preponderance, and average age of presentation in mid puberty. Presentation can range from insidious to severe, and diabetic ketoacidosis is not uncommon, which contrasts with adult-onset T2DM, in which ketoacidosis is rare. Many youth with T2DM present with classic symptoms, including weight loss. Diagnosis in asymptomatic individuals is also common, either as a consequence of the incidental finding of glucosuria or hyperglycemia or as a result of screening individuals at risk. It is likely that many individuals with youth-onset T2DM experience a prolonged period of mild hyperglycemia with minimal or no symptoms.

Distinguishing Between Type 1 and Type 2 Diabetes in Children

Both T1DM and T2DM most often present during puberty, a period of life characterized by a physiologic reduction in insulin sensitivity of approximately 30%.⁶ The increasing incidence of T2DM in youth and the current high prevalence of overweight and obesity in children and adolescents have presented clinicians with a diagnostic challenge when evaluating a patient with new-onset diabetes mellitus. Distinguishing between T1DM and T2DM may be difficult because considerable overlap in presentation may occur. The overall frequency of obesity at diagnosis of T1DM, irrespective of race, gender, and age of onset, has tripled in the past decade, and a recent report indicates that one fourth of patients with T1DM are obese.⁷ In contrast to T2DM in adults, in which ketonuria is unusual, a substantial fraction of adolescents with T2DM have ketonuria (24% to 63%) or even DKA (5% to 46%) at presentation. Insulin requirements typically decrease after several weeks of treatment for TD2M, which may resemble the remission or “honeymoon” period of T1DM. Measuring pancreatic autoantibodies and markers of insulin secretion (fasting C-peptide levels) at the time of diagnosis helps to distinguish between T1DM and T2DM in obese patients. A fasting plasma C-peptide level >0.85 ng/mL suggests T2DM.⁸ Plasma C-peptide levels, however, may initially be temporarily low in T2DM owing to glucotoxicity and lipotoxicity, and rechecking the level after several weeks or even months of therapy will sometimes demonstrate hyperinsulinism, helping to establish a diagnosis of T2DM. A recent report suggests that a fasting insulin-like growth factor binding protein-1 (IGFBP-1) level, whose secretion is acutely inhibited by insulin and, therefore, is a marker of insulin action, is another useful biochemical parameter to assist the clinician in making the distinction. An IGFBP-1 concentration ≤3.6 ng/mL is highly suggestive of T2DM.⁸ Several recent reports have described autoantibody positivity in children with clinical features of T2DM. Latent autoimmune diabetes in youth (LADY) has been proposed to describe this subgroup. A binary classification is not always possible at the time of diagnosis; clearly, some patients have clinical and biochemical features of both types of diabetes. Irrespective of the type of diabetes, the choice of initial therapy must be made on the basis of the metabolic state, as determined by clinical assessment. Subsequent therapy is then modified, if necessary, guided by the individual patient’s response to treatment.

Management of Diabetes Mellitus

Initial Management of Newly Diagnosed Type 1 Diabetes Mellitus

Whenever possible, the child with DKA should be cared for in a health care facility that has nursing staff trained in DKA management and access to a clinical chemistry laboratory that can provide frequent and timely measurement of serum chemistries. Children with signs of severe DKA (long duration of symptoms, compromised circulation, depressed level of consciousness) and those at increased risk for cerebral edema (<5 years of age, new-onset diabetes) should be treated in a pediatric intensive care unit or in a children’s ward that specializes in diabetes and can provide equivalent resources and supervision of care.⁹

The goals of initial management of the child with newly diagnosed diabetes mellitus depend on the clinical presentation and include the following: to restore fluid and electrolyte balance, to stabilize the metabolic state with insulin, and to provide basic diabetes education and self-management training for the child (when age and developmentally appropriate) and caregivers (parents, grandparents, guardians, older siblings, daycare providers, and babysitters).

The diagnosis of diabetes in a child is a crisis for the family, who require considerable emotional support and time for adjustment and healing. Shocked, grieving, and overwhelmed parents typically require at least 2 to 3 days to acquire basic or “survival” skills while they are coping with the emotional upheaval that typically follows the diagnosis of diabetes in a child. Even if they are not acutely ill, children with newly diagnosed T1DM usually are admitted to hospital for metabolic stabilization, diabetes education, and self-management training. However, outpatient or home-based management is preferred at some centers that have the appropriate resources.¹⁰ Outpatient or home-based management may offer several advantages: the stress of a hospital stay can be avoided, the outpatient setting or the patient’s home is a more natural learning environment for the child and family, and ambulatory treatment possibly reduces the cost of care for the health care system and the family. The literature comparing initial hospitalization with home-based and/or outpatient management of children who are not acutely ill with newly diagnosed T1DM has recently been critically reviewed. The results are inconclusive owing to insufficient high-quality data. The data suggest that where adequate outpatient and/or home initial management of T1DM in children at diagnosis can be provided, there is no disadvantage in terms of metabolic control nor increase in acute complications, hospitalizations, psychosocial or behavioral problems, or total costs.¹⁰ The decision concerning whether a child with newly diagnosed diabetes should be admitted to hospital depends on several factors. Of these, the most important are the severity of the child’s metabolic derangements, the family’s psychosocial circumstances, and the resources available at the treatment center.

Outpatient Diabetes Care

The Diabetes Team

Optimal care of children with T1DM is complex and time consuming. Children with diabetes should be managed by a multidisciplinary diabetes team that provides diabetes education and care in collaboration with the child’s primary care physician.¹¹ The team should consist of a pediatric endocrinologist or pediatrician with training in diabetes, a pediatric diabetes nurse educator (DNE), a dietitian trained in pediatric nutrition, and a mental health professional, either a clinical psychologist or a social worker. A member of the diabetes team should always be available by telephone to provide guidance and support to parents and patients and to respond to metabolic crises that require immediate intervention.

Initial Diabetes Education

Education is the keystone of diabetes care, and structured self-management education is vital to a successful outcome.¹¹ Diabetes education is the process of providing the person with the knowledge and skills needed to perform diabetes self-care, to manage crises, and to make lifestyle changes to successfully manage the disease. The diabetes education curriculum should be adapted to the individual child and family. Parents and children with newly diagnosed diabetes are anxious and frequently overwhelmed, and cannot assimilate a large amount of abstract information. Therefore, the education program should be staged. Initial educational goals should be limited to essential survival skills so that the child can be safely cared for at home and return to his or her daily routine. Initial diabetes education and self-management training should include information on what causes diabetes, how it is treated, how to administer insulin, basic meal planning, self-monitoring of blood glucose and ketones, recognition and treatment of hypoglycemia, and how and when to contact a member of the diabetes team for advice.

Continuing Diabetes Education and Long-Term Supervision of Diabetes Care

When the child is medically stable and parents (and other care providers) have mastered survival skills, the child is discharged from the hospital or ambulatory treatment center. In the first few weeks after diagnosis, frequent telephone contact provides emotional support, helps parents to interpret the results of blood glucose monitoring, and allows insulin doses to be adjusted, if necessary. Within a few weeks of diagnosis, many children enter a partial remission, evidenced by normal or near-normal blood glucose levels on a low dose (<0.25 U/kg/day) of insulin. By this time, most patients and parents are less anxious, have mastered basic diabetes management skills through repetition and experience, and now are more prepared to begin to learn the intricate details of intensive diabetes management. At this stage, the diabetes team should begin to provide patients and parents with the knowledge and skills they need to maintain optimal glycemic control while coping with the challenges imposed by exercise, fickle appetite and varying food intake, intercurrent illnesses, and the many other variations that normally occur in a child’s daily life. In addition to teaching facts and practical skills, the education program should promote desirable health beliefs and attitudes in the young person who has a chronic incurable disease. For some children, this may be best accomplished in a nontraditional educational setting such as a summer camp for children with diabetes. The educational curriculum must be concordant with the child’s level of cognitive development and has to be adapted to the learning style and intellectual ability of the individual child and family. Parents, grandparents, older siblings, school nurse, and other important people in the child’s life are encouraged to participate in the diabetes education program so they can share in the diabetes care and help the child to live a normal life.

In the first month after diagnosis, the patient is seen frequently by the diabetes team to review and consolidate the diabetes education and practical skills learned in the first few days and to extend the scope of diabetes self-management training. Thereafter, follow-up visits with members of the diabetes team should occur at least every 3 months. Regular clinic visits are scheduled to ensure that the child’s diabetes is being appropriately managed and the goals of therapy are being met. A focused history should obtain information about self-care behaviors, the child’s daily routines, the frequency and severity of and circumstances surrounding hypoglycemic events, and insulin doses, and blood glucose monitoring data should be reviewed. At each visit, height and weight are measured and plotted on a growth chart. The weight curve is especially helpful in assessing adequacy of therapy. Significant weight loss usually indicates that the prescribed dose is insufficient or that the patient is not receiving all the prescribed doses of insulin. A more complete physical examination should be performed at least once or twice each year, focusing on blood pressure, stage of puberty, evidence of thyroid disease, mobility of the joints of the hands, and examination of the injection sites for evidence of lipohypertrophy (from overuse of the site) or lipoatrophy.

Regular clinic visits also provide an opportunity to review, reinforce, and expand upon the diabetes self-care training begun at the time of diagnosis. The goal at each visit is to reinforce the goals of treatment while enhancing the patient’s and family’s understanding of diabetes management, the interplay of insulin, food, and exercise, and their impact on blood glucose levels. As the child’s cognitive development progresses, the child should become more involved in diabetes management and should assume increasing age-appropriate responsibility for daily self-care. Parents are encouraged to call for advice if the pattern of blood glucose levels changes between routine visits, suggesting the need to adjust the insulin dose or change the regimen. Eventually, when parents and patients have sufficient knowledge and experience, they are encouraged to independently adjust insulin dose(s).

Psychosocial Issues

The diagnosis of diabetes in a child or adolescent hurls the parent from a secure and known reality into a frightening and foreign world. At diagnosis, they grieve the loss of their healthy child and cope with such normal distress reactions as shock, disbelief and denial, fear, anxiety, anger, and blame or guilt. While grieving, parents are expected to acquire an understanding of the disease and behavioral skills to manage the illness at home and to assist the child to achieve acceptable blood glucose control. Parents should receive the support required to begin coping with their emotional distress and should not be overwhelmed by unrealistic expectations from a well-meaning diabetes treatment team.

Diabetes presents family members with the task of being sensitive to the balance between the child’s need for a sense of autonomy and mastery of self-care activities and the need for ongoing family support and involvement. The struggle to balance independence and dependence in relationships between the child and family members presents a long-term challenge and raises different issues for families at different stages of child and adolescent development. Focusing on normal developmental tasks at each stage of the child’s growth and development provides the most effective structure with which to address this concern (see reference 12 for details).

A medical social worker or clinical psychologist should perform an initial psychosocial assessment of all newly diagnosed patients to identify families at high risk who need additional services. Thereafter, patients are referred to a mental health specialist when emotional, social, environmental, or financial concerns are suspected or identified that interfere with the ability to maintain acceptable diabetes control. Some of the more common problems in families that have a child with diabetes include parental guilt resulting in poor adherence to the treatment regimen, difficulty coping with the child’s rebellion against treatment, anxiety, depression, fear of hypoglycemia, missed appointments, financial hardship, or loss of health insurance affecting the ability to attend scheduled clinic appointments and/or purchase supplies. Recurrent ketoacidosis is the most extreme indicator of psychosocial stress; management of such patients is incomplete without a comprehensive psychosocial assessment.

Treatment for pediatric diabetes is complicated by multiple factors inherent to childhood. Because childhood is characterized by cognitive and emotional immaturity, the involvement of responsible adults is essential to the treatment of pediatric diabetes. Diabetes treatment takes place within a family dynamic, and treatment-related conflicts are common, arising in part because of the natural discord in goals between caretakers and/or the child. Each phase of childhood has unique characteristics that complicate treatment, such as the unpredictable eating of toddlers and the unscheduled intense physical play of school-age children that can hinge on unpredictable factors such as the weather. Adolescence is characterized by multiple physiologic and psychosocial factors that make glycemic control more difficult. Optimal diabetes treatment should be tailored to each child, based on age, gender, family resources, cognitive ability, the schedule and activities of the child and family, and their goals and desires.

Current rates of psychological ill health in diabetic youth are disturbingly high, and longitudinal data indicate that mental health issues in childhood are likely to persist into early adulthood and possibly beyond. It is important to note that such mental health issues appear to be prognostic of maladaptive lifestyle practices and long-term problems with diabetes control and earlier than expected onset of complications. Based on these considerations, mental health should be given equivalence to, and perhaps even precedence over, other complications screening undertaken in diabetes clinics. Routine screening for behavioral disturbance should begin in children at the time of diabetes diagnosis, with further assessment of parental mental health and family functioning for those children identified as “at risk.” Interventions can then be targeted to the specific needs of individual children and families.¹³

Goals of Therapy

The Diabetes Control and Complications Trial (DCCT)14,15 and a similar smaller study in Sweden, the Stockholm Diabetes Intervention Study,¹⁶ ended the debate about whether the microvascular complications of diabetes are caused by hyperglycemia and can be prevented or ameliorated. The U.K. Prospective Diabetes Study (UKPDS) in adults with type 2 diabetes^17,18 provided additional scientific evidence for the importance of glycemic control. These clinical trials and long-term follow-up observations of the DCCT cohort unequivocally demonstrate the importance of lowering glycated hemoglobin (HbA1c) values to reduce the risk of development and progression of retinopathy, nephropathy, neuropathy, and macrovascular disease. Treatment regimens that reduce average HbA1c to ≈7% (about 1% above the upper limit of normal) are associated with fewer long-term microvascular and macrovascular complications.^14,15,19 Moreover, improved glycemic control is associated with a sustained decreased rate of development of diabetic complications.^20,21

The aim of diabetes management is to achieve recommended glycemic targets known to reduce the risk for long-term complications; however, no international consensus has been attained on appropriate targets for children of different ages. Biochemical goals of treatment for children and adolescents have recently been published by the International Society for Pediatric and Adolescent Diabetes (ISPAD): ideal <6.05%, optimal <7.5%, and suboptimal 7.5% to 9.0%; action is required when the value exceeds 9.0%.²² The ISPAD guidelines are accompanied by the following statement: “… each child should have their targets individually determined with the goal of achieving a value as close to normal as possible while avoiding severe hypoglycemia as well as frequent mild to moderate hypoglycemia.” The recommendations of a sample of national diabetes organizations are shown in Table 23-1.

Table 23-1

Recommended Glycemic Targets

^a A lower goal (<7%) is reasonable if it can be achieved without excessive hypoglycemia.

^b “In very young children, … glycaemic targets need to be at the upper part of these ranges or a little higher.”

^c Extreme caution is required to avoid severe hypoglycemia.

^d Targets should be graduated to the child’s age.

^e Appropriate for most patients.

^f Consider for patients in whom these targets can be achieved safely.

^g “… without frequent disabling hypoglycemia.”

^h These targets are intended as guidelines, and each child should have his or her targets individually determined with the goal of achieving a value as close to normal as possible while avoiding severe hypoglycemia, as well as frequent mild to moderate hypoglycemia.²²

Management of young children with diabetes, especially those younger than 5 years old, must balance opposing risks of hypoglycemia (see section on Hypoglycemia below) and future vascular complications. The relative contribution of the prepubertal years to the development of microvascular complications has been uncertain; however, recent evidence indicates that longer prepubertal duration of diabetes increases the risk for retinopathy and, possibly, microalbuminuria in adolescence and young adulthood, but at a slower rate than in the postpubertal years.²³

The risk for microalbuminuria increases steeply with HbA1c >8%.24,25 Based on these considerations, an HbA1c of ≤8.0% is a reasonable general goal for children with diabetes; however, biochemical goals should be individualized, taking into account both medical and psychosocial considerations. Less stringent treatment goals are appropriate for preschool-age children, those with developmental handicaps, psychosocial challenges, and lack of appropriate family support, for children who have experienced severe hypoglycemia or have hypoglycemia unawareness.

Insulin Therapy

Within days to months of diagnosis, most children with T1DM are severely insulin deficient and depend on insulin replacement for survival. The aim of insulin replacement therapy is to simulate as closely as possible patterns of plasma insulin levels that occur in nondiabetic individuals; however, truly physiologic replacement of insulin remains an elusive goal. Insulin pump therapy and multiple daily insulin injections are the two methods that most closely mimic insulin secretion. The first step in choosing an insulin regimen is to establish glycemic goals. For most patients, this means that more than one half of plasma glucose values should fall within the following ranges: preprandial 90 to 130 mg/dL (5 to 7.2 mmol/L), bedtime 100 to 140 mg/dL (5.6 to 7.8 mmol/L), and 1 to 2 hours postprandial <180 mg/dL (10 mmol/L) (see Table 23-1).

In children with severe insulin deficiency, practical considerations, including socioeconomic circumstances, age, supervision of care, ability and willingness to self-administer insulin several times each day, and difficulty maintaining long-term adherence, make physiologic replacement of insulin challenging. No universal insulin regimen can be successfully used for all children with T1DM. The diabetes team has to design an insulin regimen that meets the needs of the individual patient and is acceptable to the patient and/or family members(s) responsible for administering insulin to the child or supervising its administration.

The initial route of insulin administration is determined by the severity of the child’s condition at presentation. Insulin is preferably given intravenously as treatment for DKA. Children who are metabolically stable without vomiting or significant ketosis may be started with subcutaneous (SC) insulin administration. SC insulin treatment in the newly diagnosed child should, ideally, be started with at least three injections per day or a basal-bolus regimen (Table 23-2). Some clinicians have recently started insulin pump therapy at the time of diagnosis, regardless of the severity of presentation or the age of the child.

Table 23-2

Insulin Regimens Used to Treat Children and Adolescents

Det, Insulin detemir; Glarg, insulin glargine; N, neutral protamine Hagedorn (isophane); R, regular (soluble) insulin; S, short-acting insulin (insulin lispro, insulin aspart, insulin glulisine).

Insulin detemir may be used once (typically with dinner or at bedtime) or twice daily (with breakfast and a second dose with dinner or at bedtime).

Intensified insulin therapy is defined as the use of at least three daily doses of insulin or CSII.

^*Premixed combinations such as either 70% NPH and 30% regular, or 70% protamine-crystallized aspart (PA) and 30% soluble insulin aspart, or 75% neutral protamine lispro (NPL) and 25% insulin lispro are usually used in twice-daily fixed-dose insulin regimens.

^†Insulin glargine is almost always given once daily, with breakfast or in the evening with dinner or at bedtime. According to the manufacturers, both glargine and detemir should be given as a separate injection and cannot be mixed with another insulin in the same syringe. However, recent studies suggest that rapid-acting insulin analogues can be mixed with glargine in the same syringe with no detrimental effect on insulin action, provided they are injected immediately.238,239

^‡CSII, continuous subcutaneous insulin infusion (pump), boluses are given with meals and snacks together with basal insulin throughout the day and night.

In addition to severity of metabolic decompensation, the child’s age, weight, and pubertal status guide the initial insulin dose selection. When diabetes has been diagnosed early, before significant metabolic decompensation, 0.25 to 0.5 unit/kg/day usually is an adequate starting dose. When metabolic decompensation is more severe (e.g., ketosis without acidosis or dehydration) the initial dose typically is at least 0.5 unit/kg/day. After recovery from DKA, prepubertal children usually require at least 0.75 unit/kg/day, whereas adolescents require at least 1 unit/kg/day. In the first few days of insulin therapy, while the focus of care is on diabetes education and emotional support, it is reasonable to aim for pre-meal blood glucose levels in the range of 80 to 200 mg/dL and to supplement, if necessary, with 0.05 to 0.1 unit/kg of rapid-acting insulin SC at 3 to 4 hour intervals.

Three major categories of insulin preparations, classified according to their time course of action, are available (Table 23-3). Various insulin replacement regimens consisting of a mixture of short- or rapid-acting insulin and an intermediate- or long-acting insulin are used in children and adolescents (see Table 23-2) and typically are given two to four (or more) times daily. Clear superiority of any one regimen in children and adolescents, in terms of metabolic outcomes, has not been demonstrated.^26,27 All insulin regimens have the same general goal: to provide basal insulin throughout the day and night and additional (prandial) insulin to cover meals and snacks.

Table 23-3

Insulin Preparations Classified According to Their Pharmacodynamic Profiles

NPL, Neutral protamine lispro suspension; PA, protamine-crystallized insulin aspart suspension. Both PA + soluble aspart and NPL + lispro are stable premixed combinations of intermediate- and short-acting insulins.

Pharmacodynamic effects of lispro insulin and insulin aspart appear to be equivalent.²⁴⁰

The human insulins and insulin analogs are available in vials, prefilled disposable pen injectors, and cartridges for nondisposable pen injectors.

These data are for human insulins and are approximations from studies in adult test subjects. Time action profiles are estimates only. The kinetics of NPH insulin may be more rapid in children.²⁴¹ The times of onset, peak, and effective duration of action vary within and between patients and are affected by numerous factors, including size of dose, site and depth of injection, dilution, exercise, temperature, regional blood flow, and local tissue reactions.

^*Insulin analogue developed by modifying the amino acid sequence and/or chemical adducts of the human insulin molecule.

^†Dose dependent; 12 hours for 0.2 U/kg; 20-24 hours for ≥0.4 U/kg.

When a two-dose regimen is used, the total daily dose is typically divided so that about two thirds is given before breakfast and one third is given in the evening. With a three-dose regimen, short- or rapid-acting insulin is administered before the evening meal, and the second dose of intermediate- or a long-acting insulin is given at bedtime rather than before the evening meal. The initial ratio of rapid- to intermediate-acting insulin at both times is approximately 1:2. Toddlers and young children typically require a smaller fraction of short- or rapid-acting insulin (10% to 20% of the total dose) and proportionately more intermediate- or long-acting insulin. Regular insulin is given at least 30 minutes before eating; rapid-acting insulin (lispro, aspart, glulisine) is given 5 to 15 minutes before eating (depending on the pre-meal blood glucose value). In toddlers and young children with unpredictable eating habits, rapid-acting insulin may be given immediately after the meal (dose based on estimated actual carbohydrate consumed) to prevent hypoglycemia from incorrect insulin dosing owing to the child’s not eating the entire meal.28,29

The optimal ratio of rapid- or short-acting to intermediate- or long-acting insulin for each patient is determined empirically, guided by the results of frequent blood glucose measurements. At least five daily measurements are required initially to determine the effects of each component of the insulin regimen. The blood glucose concentration is measured before each meal, before the bedtime snack, and once between midnight and 4 am. Parents are taught to look for patterns of hyperglycemia or hypoglycemia that indicate the need for an adjustment in the dose. Adjustments are made to individual components of the insulin regimen, usually in 5% to 10% increments or decrements, in response to patterns of consistently elevated (above the target range for several consecutive days) or unexplained low blood glucose levels, respectively. This is referred to as pattern adjustment. The insulin dose is adjusted until satisfactory blood glucose control is achieved with at least 50% of blood glucose values in or close to the individual child’s target range.

At the time of diagnosis, most children have some residual β cell function and within several days to a few weeks often enter a period of partial remission (“honeymoon”), during which normal or nearly normal glycemia is relatively easily achieved with a low dose of insulin. At this stage, the dose of insulin should be reduced to prevent hypoglycemia but should not be discontinued. As destruction of remaining β cells occurs, the insulin dose increases (“intensification phase”), eventually reaching a full replacement dose. The average daily insulin dose in prepubertal children with long-standing diabetes is approximately 0.8 unit/kg/day, and in adolescents 1 to 1.5 units/kg/day.

Insulin Therapy in Young Children: Technical Considerations

Caring for young children with diabetes is challenging for many reasons, one of which is the need to accurately and reproducibly measure and inject tiny doses of insulin that is supplied in a concentration of 100 units/mL (U 100 insulin). To administer a dose of 1 unit requires the ability to accurately measure 10 µL (1/100 mL) of insulin. When the dose is less than 2 U of U 100 insulin, neither parents of diabetic children nor skilled pediatric nurses are able to measure the dose accurately.³⁰ Furthermore, a dose change of 0.25 U translates into a volume difference of 2.5 µL in a 300 µL (3/10 cc or 30 unit) syringe. When parents attempt to measure insulin doses in increments of 0.25 U of insulin (e.g., 3.0, 3.25, 3.5 U) using a standard commercial 30 unit (300 µL) syringe, they consistently measure more than the prescribed amount.³¹ Therefore, to enhance the accuracy and reproducibility of small doses, insulin should be diluted to U 10 (10 units/mL) with the specific diluent available from the insulin manufacturers. When U 10 insulin is used, each line (“unit”) on a syringe is actually 0.1 U of insulin.

To avoid intramuscular insulin injections in infants and young children with little subcutaneous fat, syringes with 8 mm needles or insulin pens with 31 gauge 5 mm needles should be used. Short needles (5 or 8 mm) are also desirable for use in older thin children.

Intensified Insulin Therapy in Children: Little evidence is available to guide clinical decisions concerning the risk-benefit ratio of strict control in the preadolescent patient. Clinical trials comparable to the DCCT have not been conducted in prepubertal children; nevertheless, it is reasonable to extrapolate that prepubertal children will also benefit from strict control of their diabetes.

Beyond the remission period, it generally is not possible to achieve near-normal glycemia with two injections per day without incurring a greater risk for hypoglycemia, especially during the overnight period. An important limitation of a two-dose “split-and-mixed” regimen is that the peak effect of the pre-dinner intermediate-acting insulin tends to occur at the time of lowest insulin requirement (midnight to 4 am), increasing the risk for nocturnal hypoglycemia. Thereafter, insulin action declines from 4 am to 8 am, when basal insulin requirements normally increase. Consequently, the tendency for blood glucose levels to rise before breakfast (dawn phenomenon) may be aggravated by waning insulin effect in the period before breakfast and/or by counterregulatory hormones secreted in response to a fall in blood glucose levels during sleep, resulting in post-hypoglycemic hyperglycemia (Somogyi phenomenon).

A three-dose insulin regimen with mixed short- or rapid- and intermediate-acting insulins before breakfast, only short- or rapid-acting insulin before dinner, and intermediate- or long-acting insulin at bedtime may significantly ameliorate these problems.32,33 Intensive insulin regimens that employ intermediate-acting insulin demand consistency in the daily meal schedule, amounts of food consumed at each meal, and the timing of insulin injections.

Basal-Bolus Regimens and Continuous Subcutaneous Insulin Infusion

Insulin therapy with at least three injections each day or with continuous subcutaneous insulin infusion (CSII) using an insulin pump can more closely simulate normal diurnal insulin profiles, overcome many of the limitations inherent in a two-dose regimen, and permit greater flexibility with respect to timing and content of meals. Doses of rapid-acting insulin are adjusted meal-to-meal based on preprandial glucose values, anticipated carbohydrate intake, and physical activity. A peakless long-acting insulin, such as insulin glargine or detemir, can be used to provide basal insulin (typically 40% to 60% of the total daily dose) and is used together with short- or rapid-acting insulin injected before each meal (basal-bolus regimen). Insulin glargine is an insulin analogue, produced by recombinant DNA technology, whose duration of action is approximately 24 hours. It has little peak activity and is administered once daily, either before breakfast or in the evening with dinner or at bedtime. It should be injected at about the same time each day, whereas short- or rapid-acting insulin is injected separately before each meal, whenever it is eaten. Insulin glargine has been used safely in children and adolescents,³⁴ and because it does not have the peak of activity characteristic of NPH, Lente, and Ultralente insulins,³⁵ it can reduce nocturnal hypoglycemic episodes without jeopardizing glycemic control.^33,36 More recently, insulin detemir has become available as an alternative long-acting, peakless basal insulin.³⁷ Detemir has effects similar to those of glargine during the first 12 hours after administration; thereafter its effects wane; accordingly, it usually has to be administered twice daily in patients with severe insulin deficiency.³⁸

In 1996, less than 5% of patients starting pump therapy were <20 years of age. Over the past several years, a worldwide marked increase has occurred in the number of children and adolescents using CSII (pump) therapy ³⁹; a current estimate is that more than 80,000 children and adolescents worldwide are using a pump to deliver insulin. An insulin pump has one unique advantage over insulin injections—the ability to program changes in basal dosage to meet an anticipated increase or decrease in need (Fig. 23-1C). This feature can be advantageous in combating the dawn phenomenon (especially in adolescents) or preventing hypoglycemia during or after strenuous exercise. In addition to programming various basal rates, the use of dual-wave and square-wave bolus delivery significantly lowers 4-hour postprandial blood glucose levels.⁴⁰ Also, the infusion set typically has to be replaced only every 2 to 3 days, sparing the child the discomfort of repeated injections. A meta-analysis of randomized controlled clinical trials concluded that CSII resulted in a small (≈0.5%) improvement in HbA1c.⁴¹

FIGURE 23-1 Insulin regimens. A, Schematic representation of idealized insulin action provided by a regimen consisting of a mixture of rapid-acting insulin (lispro or aspart) and intermediate-acting insulin (NPH or Lente) before breakfast, rapid-acting insulin (lispro or aspart) before supper, and intermediate-acting insulin (NPH or Lente) at bedtime. B, Schematic representation of idealized insulin action provided by an insulin regimen consisting of four daily injections: rapid-acting insulin (lispro or aspart) before each meal (B, L, S) and a separate injection of insulin glargine, at bedtime (as shown here) or at dinner or breakfast. C, Schematic representation of idealized insulin effect provided by continuous subcutaneous insulin infusion via an insulin pump with insulin aspart or lispro. In this figure, alternative basal rates are illustrated; insulin delivery is shown to decrease from midnight to 3 am and to increase before breakfast. B, Breakfast; HS, bedtime; L, lunch; S, supper. Arrows indicate times of insulin injection or bolus before meals.

Although an insulin pump is a complex and sophisticated medical device that requires extensive training in its proper use, with appropriate education and training and with support from parents and a school nurse, many children can manage the added responsibility of using an insulin pump and can benefit from its advantages.39,42 Only short- or rapid-acting insulin is used with CSII; therefore, any interruption in the delivery of insulin rapidly leads to metabolic decompensation. To reduce this risk, meticulous care must be devoted to the infusion system, and blood glucose levels must be measured at least four times daily. Increased lifestyle flexibility, reduced blood glucose variability, improved glycemic control, and reduced frequency of severe hypoglycemia are all documented advantages of CSII.³⁹ Success requires motivation to achieve normal blood glucose levels, frequent blood glucose monitoring, record-keeping, carbohydrate counting, and frequent contact with the diabetes team. Patients must understand that to be successful, CSII therapy requires more time, effort, and active involvement in diabetes care by patients and parents, as well as considerable education and support from the diabetes team. The individual who is unable to master a multiple-dose injection regimen is not likely to be successful with CSII. Despite concerns that it might have adverse psychosocial consequences owing to the added burden of treatment, especially in adolescents, the opposite effect has been observed. Short-term studies have shown that more aggressive and successful management of their diabetes by teenagers can be accompanied by enhanced psychosocial well-being.⁴³ In teenagers, CSII offers a treatment option that can lead to improved control and can lower the risk for severe hypoglycemia.⁴⁴

Owing to physiologic peripheral insulin resistance of puberty,⁴⁵ adolescents require large doses of rapid- or short-acting insulin to control postprandial blood glucose excursions. However, a large increase in the dose of regular insulin delays its peak effect (to 3 to 4 hours) and prolongs its total duration of action to 6 to 8 hours. Puberty does not cause hepatic insulin resistance; therefore, hyperinsulinemia suppresses hepatic glucose production for several hours and increases the risk for postprandial hypoglycemia, especially at night between 10 pm and 2 am.⁴⁶ This is an important reason to recommend use of rapid-acting insulin analogs (lispro, aspart, or glulisine) in preference to regular (soluble) insulin in treating adolescents, especially before the evening meal, to reduce the risk for nocturnal hypoglycemia.

Technological innovations have provided patients with insulin preparations whose pharmacokinetic properties make it possible to crudely simulate physiologic insulin kinetics. It is now possible for children to safely achieve unprecedented levels of glycemic control without excessive severe hypoglycemia. The diabetes care provider should frankly discuss treatment options with parents and child and should explain the advantages and disadvantages of each in attempting to meet the overall goals of treatment. The most suitable regimen for a given child and family should be determined by mutual consent.

Medical Nutrition Therapy

Nutritional management is one of the cornerstones of the management of all types of diabetes mellitus, and nutrition education is an essential component of a comprehensive program of diabetes education for patients and their families.⁴⁷ There is no “diabetic diet” per se. Nutrition therapy should be individualized, with consideration given to the patient’s usual eating habits and other lifestyle factors. Monitoring clinical and metabolic parameters, including height and weight, blood pressure, blood glucose, HbA1c, and lipids, as well as quality of life, is crucial to ensure successful outcomes. Diabetes management that combines frequent self-monitoring of blood glucose with intensive insulin therapy and mastery of carbohydrate counting enables children and adolescents to enjoy dietary flexibility while maintaining glycemic control in the target range.

Patients with both T1DM and T2DM have the same goals: namely, to achieve and maintain target blood glucose and HbA1c levels (Table 23-4). The initial focus of medical nutrition therapy (MNT), however, differs between the two major types of diabetes. Children with T2DM typically are obese at presentation, and great emphasis is placed on weight loss, limiting caloric intake, and distributing meals evenly throughout the day. In T2DM, even modest weight reduction alone increases sensitivity to insulin and improves fasting and postprandial plasma glucose levels. Similarly, moderate caloric reduction decreases plasma glucose levels. In adults, structured, intensive lifestyle programs involving participant education, individualized counseling, reduced energy and fat intake (30% of total energy), regular physical activity, and frequent participant contact are necessary to produce long-term weight loss of 5% to 7% of starting weight.⁴⁸ Accordingly, lifestyle changes that lead to weight loss are the cornerstone of therapy in patients with T2DM. In contrast, in the child with T1DM, the primary goal is to match insulin delivery with carbohydrate consumption to achieve blood glucose levels in the age-specific target range (see Table 23-1).

Table 23-4

Goals of Medical Nutrition Therapy for Children and Adolescents With Diabetes Mellitus

Adapted.^242,243

No evidence indicates that the nutritional needs of children with diabetes differ from those of otherwise healthy children. Therefore, nutrient recommendations are based on the requirements of healthy children and adolescents. The total intake of energy must be sufficient to balance the daily expenditure of energy and has to be adjusted periodically to achieve an ideal body weight and to maintain a normal rate of physical growth and maturation.

Carbohydrate

Approximately 60% to 70% of total energy should be obtained from carbohydrate and monounsaturated fat.⁴⁹ Dietary dogma had been to avoid simple sugars and replace them with complex carbohydrates. This belief was based on the assumption that simple sugars are more rapidly digested and absorbed than starches and would aggravate hyperglycemia to a greater degree. The glycemic index (GI), proposed in 1981 as an alternative system for classifying carbohydrate-containing foods, measures the glycemic response after ingestion of carbohydrate. GI is defined as the incremental area under the plasma glucose response curve after consumption of a standard amount of carbohydrate from a test food relative to that of a control food, either white bread or glucose. Glycemic and hormonal responses to a large number of carbohydrates have been systematically examined and their GIs defined. There is a wide spectrum of biological responses to different complex and simple carbohydrates with so much overlap that they cannot be simply classified into two distinct groups. Even a single food produces a substantially different glycemic response when prepared in different ways. The physical structure and form of a carbohydrate-containing food, in addition to its chemical composition, influence postprandial glycemia by altering its rate of digestion and absorption. Fruits and milk cause a lower glycemic response than most starches, and sucrose causes a glycemic response similar to that of bread, rice, and potatoes. In general, most refined starchy foods have a high GI, whereas nonstarchy vegetables, fruits, and legumes tend to have a low GI.

The usefulness of low-GI diets in individuals with T1DM continues to be controversial, and data are sparse in children. A meta-analysis of randomized controlled clinical trials, some of which have included children, shows that low-GI diets have modest long-term beneficial effects on blood glucose and lipid concentrations.⁵⁰

The glycemic load of meals and snacks is more important than the source or type of carbohydrate. The glycemic load, defined as the weighted average of the GI of individual foods multiplied by the percentage of dietary energy as carbohydrate, has been proposed as a method to characterize the impact of foods and dietary patterns with different macronutrient composition on glycemic responses. For example, a carrot has a high GI but a low glycemic load, whereas a potato has both a high GI and a high glycemic load. Although the use of low-GI foods may reduce postprandial glycemic excursions and may have long-term benefit on HbA1c levels, emphasis should be on the total amount of carbohydrate consumed, and its source should be a secondary consideration.⁵¹

Table 23-5

Calorie and Macronutrient Content of Exchange Lists

Table 23-6

An Example of a Patient’s Daily Food Allowance Distributed Among the Food Groups

Refer to text.

Individuals who use intensive insulin therapy usually select their pre-meal insulin doses based on the carbohydrate content of their meals, whereas individuals who receive fixed daily insulin dosages must attempt to maintain day-to-day consistency with respect to the carbohydrate content of their meals and snacks.

Fiber, which refers to the indigestible portion of a plant, influences the digestion, absorption, and metabolism of many nutrients. Inclusion of plant fiber in the diet may benefit patients with diabetes by diminishing postprandial glycemia. Certain soluble plant fibers significantly reduce serum cholesterol concentrations and decrease fasting serum triglyceride levels in patients with diabetes who have hypertriglyceridemia. Dietary fiber guidelines for children with diabetes are the same as for nondiabetic children and can be readily achieved by increasing the consumption of minimally processed foods, such as grains, legumes, fruits, and vegetables. Among diabetic adolescents using intensive insulin treatment methods, optimal blood glucose control is more common in those who have a higher intake of fiber, fruits, and vegetables.⁵²

Protein

Protein requirements are not increased when diabetes is well controlled with insulin, and children with diabetes should follow the recommended daily allowance guidelines. Physiologic requirements are determined by the amount of protein necessary to sustain normal growth, which is based on ideal weight-for-height and varies with age, being highest in infancy and early childhood. Protein intake should be 0.9 to 2.2 g/kg body weight/day and constitutes 15% to 20% of the total daily intake of energy—the same as for nondiabetic children and adolescents.

Fat

A carbohydrate-containing meal that also has a high content of saturated fat significantly increases and prolongs the glycemic effect of the meal and requires anticipatory adjustment of the dose of insulin to combat the effect. Excessive saturated fat, cholesterol, and total energy lead to increased blood levels of cholesterol and triglycerides. Because hyperlipidemia is a major determinant of atherosclerosis, and patients with T1DM eventually develop atherosclerosis and its sequelae, the meal plan should attempt to mitigate this risk factor. The consumption of saturated fat can be reduced by eating less red meat, whole milk, and high-fat dairy foods and by eating more poultry, fish, and vegetable proteins, and by drinking more low-fat milk. Children and adolescents with well-controlled T1DM are not at high risk for dyslipidemia, but they should be screened and monitored according to recommended guidelines (see Chronic Complications section below). If the child or adolescent is growing and developing normally and has normal plasma lipid levels, less than 10% of energy should come from saturated fat, the daily intake of cholesterol should be less than 300 mg/day, and consumption of transunsaturated fatty acids should be minimized. Total dietary fat should be reduced in the obese child to reduce total energy consumption. The National Cholesterol Education Program (NCEP) Step II diet guidelines should be implemented in the patient with elevated LDL cholesterol (>2.6 mmol/L [100 mg/dL]). Total fat should constitute ≤30% of total calories, with <7% of calories from saturated fat, and dietary cholesterol should be limited to 200 mg/day.⁵³

MNT Education and Formulation of the Meal Plan

Newly diagnosed children with T1DM usually present with weight loss; therefore, the initial meal plan includes an estimation of energy requirements to restore and then maintain an appropriate body weight and allow for normal growth and development. Energy requirements vary with age, height, weight, stage of puberty, and level of physical activity. Because the energy needs of growing children continuously change, the meal plan should be reevaluated at least every 6 months in young children and annually in adolescents.

MNT begins with an assessment by a registered dietitian, heeding the ethnic, religious, and economic factors pertaining to the individual patient and family. The meal plan must take account of the child’s school schedule, early or late lunches, physical education classes, after-school physical activity, and differences in a child’s activities on weekdays compared with weekends and holidays. Young children typically have three meals and two or three snacks daily, depending on the interval between meals, the age of the child, and the level of physical activity. Although their daily energy intake is relatively constant over time, young children adjust their energy intake at successive meals.⁵⁴ The highly variable food consumption from meal to meal typical of normal young children is especially challenging when the child has T1DM. Rapid-acting insulin may be administered after the meal, based on estimation of the actual amount of carbohydrate consumed, and this diminishes parental anxiety.^28,29 The purpose of snacks is to prevent hypoglycemia and hunger between meals. If the basal insulin component is adjusted appropriately, patients who use a basal-bolus insulin regimen or insulin pump therapy may not require snacks. Data from preprandial and postprandial blood glucose monitoring and individualized insulin-to-carbohydrate ratios are used to select insulin doses to match anticipated carbohydrate intake.

The dietitian’s role is to evaluate the patient’s and family’s knowledge and understanding of nutrition and to formulate an individualized meal plan. Even intensive insulin replacement regimens are not successful without careful attention to meal planning.⁵⁵ Nutrition education, like all aspects of diabetes education, has to be an ongoing process with periodic review and revision of the meal plan and assessment of the child’s and parents’ levels of comprehension, ability to analyze and solve problems, and adherence to the nutrition goals. The patient with newly diagnosed diabetes and his or her parents should consult with a dietitian several times during the first few days after diagnosis. Within a few weeks of the child resuming his or her usual schedule and activities, the patient and family should review the meal plan with a dietitian, who also should be available to patients for telephone consultation. If the patient’s glycemic control is poor, if growth is failing, if weight gain is excessive, or if other problems related to MNT should arise, the dietitian should be re-consulted.

The Meal Plan: The individualized meal plan must be simple, practical, and easy to modify, and should offer foods that are interesting, tasty, and affordable. Dietary strategies principally are determined by the patient’s insulin replacement regimen (Table 23-7). We advocate meal planning adapted to the ethnic, religious, and economic circumstances of each family and based on a combination of carbohydrate counting and the exchange system. Each list in the exchange system for meal planning indicates the appropriate size or volume of each food exchange. Each portion of food within a group is exchangeable because it contains approximately the same nutritional value in terms of calories, carbohydrates, protein, and fat. By prescribing the meal plan in terms of a number of exchanges for each meal, the consistency of total calories and the proportions of nutrients can be maintained, while allowing the patient to choose among numerous foods. Accurate measurement of portion sizes has to be learned, and weighing and measuring of foods helps to achieve familiarity with the sizes of food portions specified in the exchange list. Weighing and measuring food should be viewed as an educational exercise to train the eye and need not be continued indefinitely; however, if blood glucose control appears inexplicably to deteriorate, it is useful to resume weighing and measuring of food portions to ensure that amounts are accurate. The exchange system should not be used in isolation; rather, it should be one component of a nutritional program directed by a trained dietitian. An example of how this system is applied to a hypothetical patient is illustrated below. An 11-year-old girl’s height is 144 cm (50th percentile on the Centers for Disease Control and Prevention growth chart) and her weight is 37.4 kg (50th percentile). Her daily energy requirement to support growth in the 50th percentile is 1756 calories. An appropriate distribution of macronutrients consists of 50% of total calories from carbohydrate, 20% as protein, and 30% as fat (see Table 23-6).

Table 23-7

General Approaches to Meal Management

Exercise: Children with diabetes are encouraged to participate in sports and to include regular exercise in their lives. Participation in physical exercise normalizes the child’s life, enhances self-esteem, improves physical fitness, helps to control weight, and may improve glycemic control. Regular exercise increases insulin sensitivity, cardiovascular fitness, and lean body mass, improves blood lipid profiles, and lowers blood pressure.

Although physical exercise is complicated for the child with T1DM, especially because of the need to prevent hypoglycemia, with proper guidance and planning, exercise can be a safe and enjoyable experience.

Exercise acutely lowers the blood glucose concentration by increasing utilization of glucose to a variable degree that depends on the intensity and duration of physical activity and the concurrent level of insulin in the blood. In T1DM, increased levels of epinephrine and glucagon in response to acute strenuous anaerobic exercise may cause transient hyperglycemia for 30 to 60 minutes.

Hypoglycemia usually can be prevented by a combination of anticipatory reduction in pre-exercise insulin dose or temporary interruption or reduction of basal insulin infusion (with CSII) and/or supplemental snacks before, during, and after activity, depending on the intensity and duration of the physical activity and its timing. Nearly all forms of activity lasting longer than 30 minutes require some adjustment to food and/or insulin. Continuous moderate-intensity exercise tends to cause a lesser decline in blood glucose levels than is produced by intermittent high-intensity exercise of short duration.⁵⁶ The optimal strategy depends on the timing of the exercise relative to the child’s meal plan and on the insulin regimen. When the content and size of the snack are selected, consideration is given to several factors, including the current blood glucose level, the action of insulin most active during and after the period of anticipated exercise, the interval since the last meal, and the duration and intensity of physical activity. The appropriate amount is learned by trial and error; however, a useful initial guide is to provide up to 1 gram of carbohydrate per kg of body mass per hour of strenuous exercise. Prolonged and strenuous exercise in the afternoon or evening should be followed by a 10% to 30% reduction in pre-supper or bedtime dose of intermediate-acting insulin or long-acting insulin or an equivalent reduction in overnight basal insulin delivery in patients using CSII. In addition, to reduce the risk for nocturnal or early-morning hypoglycemia caused by the lag effect of exercise, the bedtime snack should be larger than usual and should contain carbohydrate, protein, and fat. Parents should be encouraged to monitor the blood glucose concentration in the middle of the night until they are experienced in modifying the evening dose of insulin after exercise.

Blood glucose monitoring is essential for the active child with diabetes because it allows identification of trends in glycemic responses. Records should include blood glucose levels and information on the timing, duration, and intensity of exercise, as well strategies used to maintain glucose concentrations in the target range. Blood glucose levels should be measured before, during, and after exercise and, to prevent nocturnal hypoglycemia, before bedtime (Table 23-8).

Table 23-8

Practical Guidelines for Exercise

• Consider the timing, mode, duration, and intensity of exercise.

• Eat a carbohydrate-containing meal 1 to 3 hours before exercise.

• Measure blood glucose level:

• If BG <90 mg/dL (5 mmole/L) and levels are decreasing, extra calories are needed.

Buy Membership for Endocrinology, Diabetes and Metabolism Category to continue reading. Learn more here