Type 1 diabetes is a condition in which the pancreas stops producing adequate insulin. Without insulin, the body’s cells cannot absorb glucose from the blood and use it as fuel. The glucose level in the blood keeps rising, resulting in hyperglycaemia.
Type 1 diabetes is an autoimmune condition. Specific genes and a positive family history increase the risk. Viruses (e.g., Coxsackievirus B) may be implicated in triggering the condition.
Patients with type 1 diabetes are more likely to develop:
- Autoimmune thyroid disease
- Coeliac disease
- Primary adrenal insufficiency (Addison’s disease)
- Vitiligo
- Pernicious anaemia
Presentation
About 25 – 50% of new type 1 diabetic children present in diabetic ketoacidosis (DKA).
The remaining paediatric patients present with the classic triad of symptoms of hyperglycaemia:
- Polyuria (excessive urine)
- Polydipsia (excessive thirst)
- Weight loss (through dehydration)
Less typical presentations include secondary enuresis (bedwetting in a previously dry child) and recurrent infections.
Glucose Metabolism
Carbohydrates consumed in the diet break down into monosaccharides (e.g., glucose) and are absorbed in the small intestine. Blood glucose levels rise after a meal containing carbohydrates. They fall as the cells use or store the glucose. The blood glucose concentration is ideally kept between 4.4 and 6.1 mmol/L.
Insulin is a hormone produced by the beta cells in the Islets of Langerhans in the pancreas. It is an anabolic hormone (a building hormone). Insulin acts to reduce blood sugar levels in two ways. Firstly, it causes cells in the body to absorb glucose from the blood and use it as fuel. Secondly, it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen in a process called glycogenesis.
Insulin is essential in enabling cells to take glucose out of the blood and use it as fuel. Without insulin, cells cannot take up and use glucose. It is always present in small amounts but increases when blood glucose levels rise.
Glucagon is a hormone produced by the alpha cells in the Islets of Langerhans in the pancreas. It is a catabolic hormone (a breakdown hormone). It is released in response to low blood glucose levels and stress and works to increase blood glucose levels. It tells the liver to break down stored glycogen and release it into the blood as glucose in a process called glycogenolysis. It also tells the liver to convert proteins and fats into glucose in a process called gluconeogenesis.
Ketones
Ketogenesis (the production of ketones) occurs when there is insufficient glucose supply, and glycogen stores are exhausted, such as in prolonged fasting. The liver takes fatty acids and converts them to ketones. Ketones are water-soluble fatty acids that can be used as fuel. They can cross the blood-brain barrier and be used by the brain.
Producing ketones is normal and not harmful in healthy patients under fasting conditions or on very low carbohydrate, high-fat diets. Ketone levels can be measured in the urine with a dipstick test and in the blood using a ketone meter. People in ketosis have a characteristic acetone smell to their breath.
The kidneys buffer ketone acids (ketones) in healthy people so the blood does not become acidotic. When type 1 diabetes causes extreme hyperglycaemic ketosis, the result is life-threatening metabolic acidosis. This is called diabetic ketoacidosis.
Pathophysiology of Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) occurs as a consequence of inadequate insulin. Scenarios where it occurs include:
- The initial presentation of type 1 diabetes
- An existing patient with type 1 diabetes who is unwell for another reason, often with an infection
- An existing patient with type 1 diabetes who is not adhering to their insulin regime
The key features are:
- Hyperglycaemia
- Ketoacidosis (metabolic acidosis with raised ketones and low bicarbonate)
- Dehydration
- Potassium imbalance
Without insulin, the body’s cells cannot recognise glucose, even when there is plenty in the blood, so the liver starts producing ketones for fuel. The blood glucose and ketone levels keep rising. Initially, the kidneys produce bicarbonate to counteract the ketone acids in the blood and maintain a normal pH. Over time, the ketone acids use up the bicarbonate, and the blood becomes acidic. This is called ketoacidosis.
High blood glucose (hyperglycaemia) overwhelms the kidneys, and glucose leaks into the urine. Water follows the glucose into the urine, increasing urine production (polyuria) by osmotic diuresis, resulting in dehydration. Dehydration results in excessive thirst (polydipsia).
Insulin drives potassium into cells, and without insulin, potassium is not added to the cells. Serum potassium may be high or normal, as the kidneys balance blood potassium with the potassium excreted in the urine. However, total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts, patients can develop severe hypokalaemia (low serum potassium) very quickly, leading to fatal arrhythmias.
Presentation of Diabetic Ketoacidosis
Patients with diabetic ketoacidosis may present with:
- Polyuria (high urine output)
- Polydipsia (excessive thirst)
- Nausea and vomiting
- Acetone smell to the breath
- Dehydration
- Weight loss
- Hypotension (low blood pressure)
- Altered consciousness
They may have signs and symptoms of an underlying trigger, such as an infection.
Diagnosing Diabetic Ketoacidosis
A diagnosis requires all three of:
- Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
- Ketosis (e.g., blood ketones above 3 mmol/L)
- Acidosis (e.g., pH below 7.3)
Cerebral Oedema
Children with DKA are at high risk of developing cerebral oedema when they start treatment.
Dehydration and the high blood glucose concentration cause water to move from the intracellular space in the brain to the extracellular space. This causes the brain cells to shrink and become dehydrated.
Correction of dehydration and hyperglycaemia (with fluids and insulin) causes a fall in the extracellular osmolarity and a shift in water from the extracellular space to the intracellular space in the brain cells. This causes the brain to swell and become oedematous, which can lead to brain cell destruction and death.
Neurological observations are monitored very closely (e.g., hourly). Signs of cerebral oedema during treatment for DKA include:
- Headaches
- Altered behaviour
- Bradycardia
- Changes in consciousness
- Falling serum sodium level
Management options for cerebral oedema are slowing IV fluids, IV mannitol and IV hypertonic saline. These will be guided by an experienced paediatrician.
Treatment of Diabetic Ketoacidosis
Diabetic ketoacidosis is a life-threatening emergency requiring urgent management. Follow local treatment protocols and be guided by senior paediatricians. They may require admission to a high-dependency unit and one-to-one nursing.
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis.
IV fluids using 0.9% sodium chloride with added potassium is the initial priority. IV fluids address the dehydration and dilute the glucose and ketones.
Dehydrated patients are given an initial fluid bolus of 10 ml/kg over 30 minutes (without added potassium). The remainder of their fluid deficit is corrected over 48 hours. Giving fluids more rapidly increases the risk of cerebral oedema.
The fluid deficit is approximately 5% of the body weight (e.g., 1 litre in a 20kg child) in mild-moderate and 10% (e.g., 2 litres in a 20kg child) in severe DKA. Patients are prescribed maintenance fluids plus added fluids to correct the deficit evenly over 48 hours. Online tools can be used to help with this calculation.
Maintenance fluid requirements for a 24-hour period are calculated based on the child’s weight:
- 100 ml/kg for the first 10kg, plus
- 50 ml/kg for the second 10kg, plus
- 20 ml/kg for the remaining weight (up to 75kg total)
For example, a 25 kg child with moderate diabetic ketoacidosis would receive an initial 250 ml bolus followed by 2100 ml per day. The way 2100 ml is calculated is maintenance fluids (1600 ml/day) plus fluids to correct the deficit over 48 hours. Their starting fluid deficit is 1.25 litres (calculated as 5% of 25kg). Minus the 250 ml bolus is 1000 ml. Divided by two to get the daily requirement is 500 ml.
A fixed-rate insulin infusion (typically 0.05-0.1 units/kg/hour) is started 1-2 hours after starting the IV fluids. Insulin allows cells to start using glucose again and switches off the production of ketones.
Other important principles:
- Treat underlying triggers (e.g., antibiotics for bacterial infections)
- Prevent hypoglycaemia with IV glucose once the blood glucose falls below 14mmol/l
- Include potassium in IV fluids (40 mmol/litre) and monitor serum potassium closely
- Monitor for signs of cerebral oedema
- Monitor glucose, ketones and pH to assess progress and determine when to switch to subcutaneous insulin
Severely unwell children may require:
- Nasogastric tube (reduced consciousness and vomiting)
- Airway protection (reduced consciousness)
- Additional fluid boluses (under expert guidance)
- Inotropes (shock)
The key complications during treatment are:
- Hypoglycaemia (low blood glucose)
- Hypokalaemia (low potassium)
- Cerebral oedema
- Pulmonary oedema
Long-Term Management
Monitoring and treatment are relatively complex. Type 1 diabetes is life-long and requires the patient and parents to understand and engage fully. It involves the following components:
- Subcutaneous insulin
- Monitoring dietary carbohydrate intake
- Monitoring blood glucose levels upon waking, at each meal and before bed
- Monitoring for and managing short-term and long-term complications
A honeymoon phase can occur shortly after being diagnosed and starting treatment. During this period, the beta cells are still producing some insulin, and the blood glucose levels can be easier to manage. Patients may require less or no insulin to maintain their target glucose levels. The honeymoon phase can last weeks or months. However, it is temporary, and eventually, the remaining beta cells in the pancreas stop functioning.
Basal-Bolus Regime
A basal-bolus regime of insulin involves a combination of:
- Background long-acting insulin injected once a day
- Short-acting insulin injected 30 minutes before consuming carbohydrates (e.g., at meals)
Injecting into the same spot can cause lipodystrophy, where the subcutaneous fat hardens. Areas of lipodystrophy do not absorb insulin properly from further injections. For this reason, patients should cycle their injection sites. If a patient is not responding to insulin as expected, ask where they inject and check for lipodystrophy.
Insulin Pumps
Insulin pumps are small devices that continuously infuse insulin at different rates to control blood sugar levels. They are an alternative to basal-bolus regimes. The pump pushes insulin through a small plastic tube (cannula) inserted under the skin. The cannula is replaced every 2-3 days, and the insertion sites are rotated to prevent lipodystrophy and absorption issues.
The advantages of an insulin pump are better blood glucose control, more eating flexibility, and fewer injections.
The disadvantages are:
- Difficulties learning to use the pump
- Having it attached at all times
- Blockages in the infusion set
- A small risk of infection
Tethered pumps are devices with replaceable infusion sets and insulin. They are usually attached to the patient’s belt or around the waist with a tube connecting the pump to the insertion site. The controls for the infusion are on the pump itself.
Patch pumps sit directly on the skin without any visible tubes. When they run out of insulin, the entire patch pump is disposed of, and a new pump is attached. A separate remote usually controls patch pumps.
Monitoring
HbA1c measures glycated haemoglobin, which is how much glucose is attached to the haemoglobin molecule. This reflects the average glucose level over the previous 2-3 months (red blood cells have a lifespan of about 4 months).
Capillary blood glucose (finger-prick test) can be measured using a blood glucose monitor, giving an immediate result. Patients use this for self-monitoring their glucose levels.
Continuous glucose monitors use a sensor on the skin that measures the glucose level of the interstitial fluid in the subcutaneous tissue. The sensor records the glucose readings at short intervals and sends these readings to the patient’s phone, giving an excellent record of the glucose levels over time. Sensors need replacing regularly (e.g., every 2 weeks). There are two options:
- Continuous glucose monitors send the readings wirelessly
- Flash glucose monitors require the patient to swipe their phone across the sensor to collect the readings
Short-Term Complications
Short-term complications relate to immediate insulin and blood glucose management:
- Hypoglycaemia (low glucose level)
- Hyperglycaemia (and diabetic ketoacidosis)
Hypoglycaemia may be caused by:
- Too much insulin
- Inadequate carbohydrates for the insulin administered
- Not processing the carbohydrates correctly (e.g., in malabsorption, diarrhoea or vomiting)
Most patients are aware of when they are hypoglycaemic by their symptoms. However, some patients can be unaware until they become severely hypoglycaemic. Typical symptoms are hunger, tremor, sweating, irritability, dizziness and pallor. More severe hypoglycaemia will lead to reduced consciousness, coma and death unless treated.
Hypoglycaemia needs to be treated initially with rapid-acting glucose (e.g., a high-sugar-content drink). Once the blood glucose improves, they consume slower-acting carbohydrates (e.g., biscuits or toast) to prevent it from dropping again. Options for treating severe hypoglycaemia are IV dextrose and intramuscular glucagon.
Hyperglycaemia is a high blood glucose level. Hyperglycaemia (without DKA) may indicate that the insulin dose needs to be increased. Short episodes of hyperglycaemia do not necessarily require treatment. Insulin injections can take several hours to take effect, and repeated doses could lead to hypoglycaemia. It is essential to exclude diabetic ketoacidosis (check for ketones). Patients meeting the criteria for DKA need admission for inpatient management.
Long Term Complications
Type 1 diabetes can impair growth during childhood.
Chronic hyperglycaemia damages the endothelial cells of blood vessels, leading to leaky, malfunctioning vessels that cannot regenerate. Over time, microvascular and macrovascular complications can develop.
Microvascular complications include:
- Retinopathy
- Kidney disease, particularly glomerulosclerosis
- Periodontitis (gum disease)
- Peripheral neuropathy
- Gastroparesis (delayed gastric emptying)
Macrovascular complications include:
- Coronary artery disease (a significant cause of death in people with diabetes)
- Peripheral ischaemia, causing poor skin healing and diabetic foot ulcers
- Stroke
- Hypertension
Hyperglycaemia causes immune system dysfunction and creates an optimal environment for infectious organisms.
Infection-related complications include:
- Urinary tract infections
- Pneumonia
- Skin and soft tissue infections, particularly in the feet
- Fungal infections, particularly oral and vaginal candidiasis
Last updated February 2025
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