Endocrine and metabolic disorders

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Last modified 21/03/2015

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Endocrine and metabolic disorders

Points of note concerning endocrine and metabolic disorders in children are:

Diabetes mellitus

The incidence of diabetes in children has increased steadily over the last 20 years and now affects around 2 per 1000 children by 16 years of age. It has been estimated that the incidence of childhood diabetes will double by 2020 in developed countries. This is most likely to be a result of changes in environmental risk factors, although the exact causes remain obscure. There is considerable racial and geographical variation – the condition is more common in northern countries, with high incidences in Scotland and Finland. Almost all children have type 1 diabetes requiring insulin from the outset. Type 2 diabetes due to insulin resistance is starting to occur in childhood, as severe obesity becomes more common and in some ethnic groups. The other causes of diabetes are listed in Box 25.1.

Aetiology of type 1 diabetes

Both genetic predisposition and environmental precipitants play a role. Inherited susceptibility is demonstrated by:

Molecular mimicry probably occurs between an environmental trigger and an antigen on the surface of β-cells of the pancreas. Triggers which may contribute are enteroviral infections, accounting for the more frequent presentation in spring and autumn, and diet, possibly cow’s milk proteins (Fig. 25.1) and overnutrition. In genetically predisposed individuals, this results in an autoimmune process which damages the pancreatic β-cells and leads to increasing insulin deficiency. Markers of β-cell destruction include islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD), the islet cells and insulin. There is an association with other autoimmune disorders such as hypothyroidism, Addison disease, coeliac disease and rheumatoid arthritis in the patient or family history.

Clinical features

There are two peaks of presentation of type 1 diabetes, preschool and teenagers. It is also commoner to present in spring and autumn months. In contrast to adults, children usually present with only a few weeks of polyuria, excessive thirst (polydipsia) and weight loss; young children may also develop secondary nocturnal enuresis. Most children are diagnosed at this early stage of the illness (Box 25.2). Advanced diabetic ketoacidosis has become an uncommon presentation (<10% in some areas of the UK), but requires urgent recognition and treatment. Diabetic ketoacidosis may be misdiagnosed if the hyperventilation is mistaken for pneumonia or the abdominal pain for appendicitis or constipation.

Initial management of type 1 diabetes

As type 1 diabetes in childhood is uncommon (1–2 children per large secondary school), much of the initial and routine care is delivered by specialist teams (Box 25.3).

The initial management will depend on the child’s clinical condition. Those in advanced diabetic ketoacidosis require urgent hospital admission and treatment (see below). Most newly presenting children are alert and able to eat and drink and can be managed with subcutaneous insulin alone. Intravenous fluid is required if the child is vomiting or dehydrated. In most centres with sufficient resources, children newly presenting with diabetes who do not require intravenous therapy are not admitted to hospital but are managed entirely at home.

An intensive educational programme is needed for the parents and child, which covers:

• A basic understanding of the pathophysiology of diabetes

• Injection of insulin: technique and sites

• Diet: reduced refined carbohydrate; healthy diet with no more than 30% fat intake; ‘carbohydrate counting’, estimating the amount of carbohydrate in food to allow calculation of the insulin required for each meal or snack

• Adjustments of diet and insulin for exercise

• ‘Sick-day rules’ during illness to prevent ketoacidosis

• Blood glucose (finger prick) monitoring and blood ketones when unwell

• The recognition and staged treatment of hypoglycaemia

• Where to get advice 24 hours a day

• The help available from voluntary groups, e.g. local groups or ‘Diabetes UK’

• The psychological impact of a lifelong condition with potentially serious short- and long-term complications.

A considerable period of time needs to be spent with the family to provide this information and psychological support. The information provided for the child must be appropriate for age, and updated regularly. The specialist nurse should liaise with the school (teachers, those who prepare school meals, physical education teachers) and the primary care team.

Insulin

Insulin is made chemically identical to human insulin by recombinant DNA technology or by chemical modification of pork insulin. All insulin that is used in the UK in children is human and in concentrations of 100 U/ml (U-100). The types of insulin include:

• Human insulin analogues. Rapid-acting insulin analogues, e.g. insulin lispro, insulin glulisine or insulin aspart (trade names Humalog, Apidra and NovoRapid, respectively) – with a much faster onset and shorter duration of action than soluble regular insulin. There are also very long-acting insulin analogues, e.g. insulin detemir (Levemir) or glargine (Lantus)

• ‘Short-acting’ soluble human regular insulin. Onset of action (30–60 min), peak 2–4 h, duration up to 8 h. Given 15–30 min before meals. Trade named examples are Actrapid and Humulin S

• Intermediate-acting insulin. Onset 1–2 h, peak 4–12 h. Isophane insulin is insulin with protamine, e.g. Insulatard and Humulin I

• Predetermined preparations of mixed short- and intermediate-acting insulins with 25% or 30% rapid-acting components.

Insulin can be given by continuous infusion of rapid-acting insulin from a pump or by injections using a variety of syringe and needle sizes, pen-like devices with insulin-containing cartridges, and jet injectors that inject insulin needle-free as a fine stream into the subcutaneous tissue.

Insulin may be injected into the subcutaneous tissue of the upper arm, the anterior and lateral aspects of the thigh, the buttocks and the abdomen. Rotation of the injection sites is essential to prevent lipohypertrophy or, more rarely, lipoatrophy. The skin should be pinched up and the insulin injected at a 45° angle. Using a long needle or an injection technique that is ‘too vertical’ causes a painful, bruised intramuscular injection. Shallow intradermal injections can also cause scarring and should be avoided.

Most children are started on an insulin pump or a 3–4 times/day injection regimen (‘basal-bolus’) with short-acting insulin (e.g. Lispro, Glulisine or Insulin Aspart) being given (bolus) before each meal and snack plus long-acting insulin (e.g. Glargine or Detemir) in the late evening and/or before breakfast to provide insulin background (basal). These treatments both allow greater flexibility by relating the insulin more closely to food intake and exercise (Fig. 25.3). Patients and families are also taught how to correct any sugar above 10 mmol/L between usual meal times by extra short-acting insulin injections. However, the input required by the teams to start these intensive regimens is high, as is the need for a supportive school environment, and some patients and families still rely on twice-daily treatment with premixed insulin.

Shortly after presentation, when some pancreatic function is preserved, insulin requirements often become minimal, the so-called ‘honeymoon period’. Requirements subsequently increase to 0.5–1 U/kg or even up to 2 U/kg per day during puberty.

Diet

The diet and insulin regimen need to be matched (Fig. 25.4). The aim is to optimise metabolic control while maintaining normal growth. A healthy diet is recommended, with a high complex carbohydrate and relatively low fat content (<30% of total calories). The diet should be high in fibre, which will provide a sustained release of glucose, rather than refined carbohydrate, which causes rapid swings in glucose levels. ‘Carbohydrate counting’ allows patients to calculate their likely insulin requirements once their food choice for a meal is known, and taking into account their pre-meal sugar level and post-meal exercise pattern. Learning this balancing act requires a lot of educational input followed by refinement in the light of experience.

Blood glucose monitoring

Regular blood glucose profiles and blood glucose measurements, when a low or high level is suspected, are required to adjust the insulin regimen and learn how changes in lifestyle, food and exercise affect control. A record should be kept in a diary or transferred from the memory of the blood glucose meter. The aim is to maintain blood glucose as near to normal (4–6 mmol/L) as possible. In practice, in order also to avoid hypoglycaemic episodes, this means levels of 4–10 mmol/L in children and 4–8 mmol/L in adolescents for as much of the time as possible. Realistic goals need to be agreed, with compromises reached about the frequency of monitoring and lifestyle issues, especially in teenagers. During changes in routine (e.g. holidays) or illness, it is not unreasonable to ask for four or more tests per day. In reality, many adolescents test less than once per week, if at all.

Continuous glucose monitoring sensors (CGMS), using subcutaneous or transcutaneous sensors to provide a continuous reading of blood glucose, are now widely available, and refinement is underway to allow these devices to help control the insulin delivered from a pump, or to suggest doses for a given meal composition and size. Continuous glucose monitoring sensors also allow the detection of unexpected asymptomatic episodes of nocturnal hypoglycaemia or times of poor control during the day. Blood ketone testing (often using the same meter as for blood glucose) is mandatory during infections or when control is poor to try to avoid severe ketoacidosis. Urine ketone testing is still used in some centres.

The measurement of glycosylated haemoglobin (HbA1c) is particularly helpful as a guide of overall control over the previous 6–12 weeks and should be checked at least 3 times per year. The level is related to the risk of later complications in a non-linear fashion, such that the risk of complications increases more rapidly with higher levels, but may be misleading if the red blood cell lifespan is reduced, such as in sickle cell trait or if the HbA molecule is abnormal, as in thalassaemia. Since 2009, the units of HbA1c (originally expressed as a % figure) have been changed to an international reporting standard of mmol/mol. Until 2012, results will be reported in both old and new units to give everyone time to become familiar with the new units. A level of ≤58 mmol/mol (7.5%) is seen as an ideal target for patients, but in practice is only achieved in 50% or less of a clinic population in the UK.

Hypoglycaemia

Most children develop well-defined symptoms when their blood glucose falls below about 4 mmol/L. The symptoms are highly individual and change with age, but most complain of hunger, tummy ache, sweatiness, feeling faint or dizzy or of a ‘wobbly feeling’ in their legs. If unrecognised or untreated, hypoglycaemia may progress to seizures and coma. Parents can often detect hypoglycaemia in young children by their pallor and irritability, sometimes presenting as unreasonable behaviour. If there is any doubt, the blood glucose concentration should be checked or food given.

Treating a ‘hypo’ at an early stage requires the administration of easily absorbed glucose in the form of glucose tablets (e.g. Lucozade tablets or similar) or a non-diet sugary drink. Children should always have easy access to their hypo remedy, although young children quickly learn to complain of hypo-symptoms in order to leave class or obtain a sweet drink! Oral glucose gels (e.g. Glucogel) are easily and quickly absorbed from the buccal mucosa and so are helpful if the child is unwilling or unable to cooperate to eat. It can be administered by teachers or other helpers. Parents and school should be provided with a glucagon injection kit for the treatment of severe hypoglycaemia, and taught how to administer it intramuscularly to terminate severe hypos. After treatment of ‘hypos’, parents or carers should give the child some food (usually a biscuit or sandwich) to ensure the blood glucose does not drop again.

Severe hypoglycaemia can usually be predicted (or explained in retrospect – missed meal, heavy exercise). The aim is anticipation and prevention. Hypoglycaemia in an unconscious child brought to hospital is treated with glucose given intravenously.

Long-term management

The aims of long-term management are:

These aims are difficult to achieve in all patients at all stages of their condition.

Problems in diabetic control

Good blood glucose control is particularly difficult in the following circumstances:

• Eating too many sugary foods, such as sweets taken at odd times, at parties or on the way home from school

• Infrequent or unreliable blood glucose testing. ‘Perfect’ results are often invented and written down just before clinic to please the diabetes team

• Illness – viral illnesses are common in the young and although it is usually stated that infections cause insulin requirements to increase, in practice the insulin dose required is variable, partly because of reduced food intake. The dose of insulin should be adjusted according to regular blood glucose monitoring. Insulin must be continued during times of illness and the urine or blood tested for ketones. If ketosis is increasing along with a rising blood sugar, the family should know how to seek immediate advice to ensure that they increase the soluble insulin dose appropriately or seek medical help for possible intravenous therapy

• Exercise – vigorous or prolonged planned exercise (cross-country running, long-distance hiking, skiing) requires reduction of the insulin dose and increase in dietary intake. Late hypoglycaemia may occur during the night or even the next day, but may be avoided by taking an extra bedtime snack, including slow-acting carbohydrate such as cereal or bread. Less vigorous exercise such as sports lessons in school and spontaneous outdoor play can be managed with an extra snack or a reduction in short-acting insulin before the exercise

• Eating disorders, which are common in young females with diabetes.

• Family disturbance such as divorce or separation

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