Paediatric Hypoglycaemia in Diabetes Mellitus

Blood glucose below 4 mmol/L in a child with diabetes, with or without symptoms. The threshold is set higher than the adult emergency threshold deliberately, because it is an alert value at which action is taken to prevent progression rather than a value at which harm has already occurred.

Why the threshold is 4 and not 3.3

Counterregulatory hormone release begins at around 3.8 mmol/L. Acting at 4 mmol/L intervenes before the child becomes symptomatic and before the counterregulatory response is exhausted. In children with recurrent hypoglycaemia the counterregulatory threshold falls, so waiting for symptoms means waiting until neuroglycopenia is already established. The practical instruction taught to families is: four is the floor.

Severity classification, which determines the route of treatment

• Mild to moderate: the child recognises the symptoms and can self treat or be treated orally. This includes any child who is alert and able to swallow safely.
• Severe: altered consciousness, seizure, or inability to take oral carbohydrate safely. Severe hypoglycaemia is defined by the need for third party assistance and by the inability to use the oral route, not by a particular glucose value.

Why the developing brain is at greater risk

The child brain has a higher glucose requirement per unit body weight, limited glycogen and gluconeogenic capacity, and is undergoing active myelination and synaptogenesis. Repeated severe hypoglycaemia in young children, particularly under 6 years, is associated with measurable deficits in memory, attention and executive function, and with structural change on imaging. This is the reason hypoglycaemia is prevented rather than simply treated, and why glycaemic targets in very young children are set less aggressively than in adolescents.

Causes in a child with diabetes

• Excess insulin: dosing error, wrong pen or wrong insulin, a decimal point error, double dosing when a parent and a child both administer, or injection into a lipohypertrophied site producing erratic absorption.
• Mismatched carbohydrate: missed or delayed meal, refused food, reduced appetite during intercurrent illness, or carbohydrate counting error.
• Exercise, which increases glucose uptake during activity and for up to 24 hours afterwards, producing the characteristic delayed nocturnal hypoglycaemia after afternoon sport.
• Vomiting and gastroenteritis with reduced intake.
• Alcohol in adolescents, which inhibits gluconeogenesis and produces delayed hypoglycaemia several hours later, often overnight, and which is frequently concealed.
• Hot weather, hot baths and massage of the injection site, all of which accelerate absorption.
• Coeliac disease with malabsorption, which occurs in 3 to 10 percent of children with type 1 diabetes and which presents with unexplained recurrent hypoglycaemia.
• Addison disease and hypothyroidism, both of which are more common in type 1 diabetes and both of which reduce insulin requirements.
• Renal impairment reducing insulin clearance.
• Deliberate insulin administration or omission in the context of psychological difficulty, eating disorder or abuse, which must be considered in a child with recurrent unexplained severe events.

Hypoglycaemia unawareness

Repeated episodes blunt the counterregulatory and symptomatic response, so the child proceeds directly to neuroglycopenia without warning. It is reversible over several weeks by scrupulous avoidance of any glucose below 4 mmol/L, which is a specific treatment goal rather than general advice, and it justifies temporarily relaxing glycaemic targets.

The symptoms are grouped because families are taught to recognise them by group, and because the group present indicates how far the episode has progressed.

Autonomic, appearing first

Shakiness, sweatiness, trembling, palpitations and pallor. Pallor and sweating are the signs a parent notices before the child reports anything, and in a preverbal child they may be the only indicators.

Neuroglycopenic, indicating cerebral glucose deprivation

Poor concentration, blurred or double vision, disturbed colour vision, difficulty hearing, slurred speech, poor judgement, confusion, problems with short term memory, dizziness, unsteady gait, loss of consciousness and seizure. These indicate a more advanced episode and, in a child who has no autonomic warning, they are the presenting features.

Behavioural

Irritability, erratic behaviour, agitation, nightmares and inconsolable crying. In toddlers and young children behavioural change is frequently the only manifestation, and it is misattributed to tiredness or temper. Any sudden unexplained change in behaviour in a child with diabetes is hypoglycaemia until the glucose is checked.

Non specific

Hunger, headache, nausea and tiredness.

Nocturnal hypoglycaemia, which is common and under recognised: night sweats with damp bedding and nightwear, nightmares, restless sleep, morning headache, and difficulty rousing. Ask about these specifically, since they are not volunteered and they indicate a pattern requiring insulin adjustment.

The diagnosis requires the symptoms plus a blood glucose below 4 mmol/L in a child with diabetes. Where a meter is not immediately available and the picture is compatible, treat first and measure afterwards.

Features indicating a severe episode requiring the parenteral route

Reduced level of consciousness, inability to follow instructions, inability to swallow safely, seizure, and any child who is not alert.

• Capillary blood glucose immediately in any child with diabetes who is unwell, behaving abnormally, drowsy, fitting or unconscious. This is a bedside test taking seconds and its omission is a recurrent cause of harm.
• Confirm with a laboratory glucose where feasible, without delaying treatment, since meters are less reliable at low values and in poor peripheral perfusion.
• Assess conscious level using AVPU or the Glasgow Coma Scale, and determine specifically whether the child can swallow safely, since this single determination directs the entire treatment pathway.
• Check blood or urine ketones, since a child who is hypoglycaemic with ketones has been fasting or vomiting and needs carbohydrate rather than insulin, while a child who is hypoglycaemic without ketones has received excess insulin.
• Where the child is not known to have diabetes, or the cause is unclear, draw a critical sample before giving glucose if this can be done in seconds: insulin, C peptide, beta hydroxybutyrate, cortisol, growth hormone, lactate, ammonia, free fatty acids, acylcarnitine profile and urine organic acids. Once glucose is given the diagnostic opportunity is lost, and in a child this may be the only chance to diagnose an inborn error of metabolism, hyperinsulinism or adrenal insufficiency. Never delay treatment for the sample in a child who is fitting or unconscious.
• Investigate recurrent unexplained hypoglycaemia: coeliac serology with tissue transglutaminase antibodies and total immunoglobulin A, thyroid function, early morning cortisol or a short synacthen test, renal function and full blood count.
• Review the insulin regimen, the injection sites for lipohypertrophy, the meter and its calibration, and the download from any pump or continuous glucose monitor, which frequently reveals the pattern that the history does not.

The pathway divides on a single question: is the child alert and able to swallow safely.

Alert child

• Give 0.3 g/kg of rapidly acting carbohydrate. In a child of around 50 kg this equates to approximately 15 g.
• Examples of 15 g of rapidly acting carbohydrate: 3 glucose tablets; 3 teaspoons of sugar or glucose dissolved in water; 175 mL, that is three quarters of a cup, of fruit juice; or 3 teaspoons of honey. Honey must not be given to infants under 12 months because of the risk of infant botulism.
• Avoid chocolate, milk and other foods containing fat, since fat delays gastric emptying and slows glucose absorption. Chocolate is the food most commonly reached for by families and is the wrong choice in an acute episode.
• Retest the blood glucose after 15 minutes.
• If there is no response or an inadequate response, repeat the oral carbohydrate. Repeat the cycle of treat, wait 15 minutes and retest until the glucose is above 4 mmol/L.
• Once the hypoglycaemia is reversed, if the next meal is more than 1 hour away, follow with 15 g of slower acting carbohydrate such as bread, milk, biscuits or fruit. Omitting this step is the commonest cause of recurrence within the hour, and it is the step families most often skip once the child feels better.
• Keep the child under observation for recurrence, particularly where the cause was excess insulin, exercise or alcohol, all of which have effects that outlast the initial correction.

Not alert, or unable to swallow safely

Any of the following three options may be used, chosen by what is immediately available.

Intravenous dextrose, where access exists

• 10 percent dextrose 5 mL/kg as a bolus over 2 to 3 minutes, which delivers 0.5 g/kg of glucose.
• Use 10 percent rather than higher concentrations in children. Concentrations of 25 and 50 percent are hyperosmolar, cause venous sclerosis and severe extravasation injury, and in the very young provoke rebound hyperinsulinaemic hypoglycaemia. Where only 50 percent dextrose is available, dilute it: 50 mL of 50 percent dextrose made up to 250 mL with normal saline gives 10 percent dextrose.
• Follow the bolus with a continuous infusion of 10 percent dextrose at maintenance rates where the child is unable to eat or where the cause is long acting, since a bolus alone lasts minutes.

Glucagon, where there is no intravenous access

• Glucagon by intravenous, intramuscular or subcutaneous route.
• 1 mg for children above 25 kg.
• 0.5 mg for children below 25 kg.
• Onset within 10 to 15 minutes. Vomiting afterwards is common and should be anticipated, with the child positioned to protect the airway.
• Contraindicated, or more accurately ineffective, in prolonged fasting, since it acts by mobilising hepatic glycogen and there is none to mobilise. The same applies after alcohol, in malnutrition, in liver disease and after a prolonged episode. In these situations glucagon will fail and intravenous dextrose must be obtained.
• Establish intravenous access as soon as possible after giving glucagon and give dextrose, since the glucagon effect is short lived and the child will relapse.
• Every family of a child on insulin should have a glucagon kit at home, in date, with at least two people trained to use it. Check this at every clinic visit.

Buccal glucose, where neither access nor glucagon is available

• Place the child in the lateral position to prevent aspiration.
• Smear glucose gel or a thick paste of glucose on the dependent cheek pad.
• Do not pour liquid into the mouth of a child who is not alert, and do not attempt to make an obtunded child swallow, since aspiration is a real and avoidable harm.
• This is a holding measure while access or glucagon is obtained, not a definitive treatment.

After correction

• Recheck the glucose at 15 minutes and then every 30 to 60 minutes until stable.
• Give a complex carbohydrate meal or snack once the child is alert and swallowing safely.
• Continue a 10 percent dextrose infusion where the child cannot eat, where the cause is a long acting insulin, or where the episode recurs.
• Identify the cause. This is the part most often omitted, and without it the episode repeats.
• Adjust the insulin regimen. Do not discharge a child on the same regimen at the same doses that produced a severe event.
• Treat any precipitating illness.
• Manage seizure with the standard approach if it does not terminate with glucose correction, recognising that a hypoglycaemic seizure usually stops within minutes of correction and that a persisting seizure requires another explanation.

Admission criteria

• Severe hypoglycaemia with seizure or loss of consciousness.
• Recurrent hypoglycaemia despite treatment.
• Hypoglycaemia with vomiting or inability to maintain oral intake.
• Hypoglycaemia from a long acting insulin or sulfonylurea, which requires prolonged observation.
• No identifiable cause.
• Concerns about the home environment, supervision, safeguarding or the family's capacity to manage.
• Any child in whom the episode reflects a systemic problem with diabetes management rather than an isolated event.

Prevention, which is where most of the benefit lies

• Structured education for the child, the family, and critically the school, since a large proportion of episodes occur at school and school staff are often untrained.
• A written hypoglycaemia plan held at home and at school, naming who does what.
• Glucagon available at home and at school with trained personnel.
• Glucose testing before and after exercise, with additional carbohydrate before activity and a reduction in the insulin dose covering the period of and following exercise, together with a bedtime snack after afternoon sport to prevent delayed nocturnal hypoglycaemia.
• Sick day rules: never omit insulin during illness, test more frequently, maintain carbohydrate intake, and use sugar containing fluids if unable to eat.
• Review injection sites at every visit and rotate them, since lipohypertrophy is common, easily palpable and a frequent cause of erratic absorption.
• Continuous glucose monitoring with alarms where available, which substantially reduces severe hypoglycaemia and is particularly valuable in young children, in hypoglycaemia unawareness and in nocturnal events.
• Relax glycaemic targets temporarily and avoid all readings below 4 mmol/L for several weeks in a child with hypoglycaemia unawareness, to restore the warning symptoms.
• Age appropriate targets, accepting that very young children, who cannot recognise or report symptoms, warrant a higher target than adolescents.
• Psychological assessment where episodes are recurrent, unexplained or associated with insulin manipulation, since fear of hypoglycaemia, eating disorder, family conflict and deliberate manipulation all present this way.
• Screen for coeliac disease, thyroid disease and adrenal insufficiency in recurrent unexplained hypoglycaemia.
• Advise adolescents explicitly about alcohol: eat carbohydrate before and during drinking, never omit the bedtime snack, test overnight, and tell a friend, since hypoglycaemia after alcohol is delayed, severe and frequently mistaken for intoxication.