Paediatric Endocrinology Flashcards
Type 1 Diabetes Mellitus
Type 1 diabetes mellitus (T1DM) is a disease where the pancreas stops being able to produce insulin. What causes the pancreas to stop producing insulin is unclear. There may be a genetic component. It may be triggered by certain viruses, such as the Coxsackie B virus and enterovirus.
When the pancreas is not producing insulin, the cells of the body cannot take glucose from the blood and use it for fuel. Insulin acts like a key that lets glucose into the cell. Therefore, when there is no insulin, the cells think there is no glucose in the blood and the body is being fasted. The cells cannot use glucose, so the level of glucose in the blood keeps rising, causing hyperglycaemia.
Basic Physiology
Eating carbohydrates causes a rise in blood glucose (sugar) levels. As the body uses these carbohydrates for energy there is a fall in blood glucose levels. The body ideally wants to keep the blood glucose concentration between 4.4 and 6.1 mmol/l.
Insulin is a hormone produced by the pancreas that reduces blood sugar levels. Insulin is produced by the beta cells in the Islets of Langerhans in the pancreas. It is an anabolic hormone (a building hormone). It is always present in small amounts, but increases when blood sugar levels rise.
Insulin reduces blood sugar in two ways: Firstly, it causes cells 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. Insulin is essential in letting cells take glucose out of the blood and use it as fuel. Without insulin, cells cannot take up and use glucose.
Glucagon is a hormone that increases blood sugar levels. It is 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 sugar levels and stress. It tells the liver to break down stored glycogen into glucose. This process is called glycogenolysis. It also tells the liver to convert proteins and fats into glucose. This process is called gluconeogenesis.
Ketogenesis occurs when there is insufficient supply of glucose, and glycogens 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 when under fasting conditions or on a very low carbohydrate, high fat diet. People in ketosis have a characteristic acetone smell to their breath.
Presentation of type 1 DM
About 25 – 50% of new type 1 diabetic children present in diabetic ketoacidosis (DKA). This is the result of a situation where the pancreas can no longer produce enough insulin to maintain basic blood glucose regulation.
The remaining paediatric patients present with the classic triad of symptoms of hyperglycaemia:
Polyuria (excessive urine)
Polydipsia (excessive thirst)
Weight loss (mostly through dehydration)
Other less typical presentations include secondary enuresis (bedwetting in a previously dry child) and recurrent infections. Symptoms are usually present from 1 to 6 weeks prior to developing DKA, however this can vary significantly.
New diagnosis of type 1 DM
When a new diagnosis is established the following bloods should be taken to exclude other associated pathology and get a baseline idea of the child’s overall health:
Baseline bloods including FBC, renal profile (U&E) and a formal laboratory glucose
Blood cultures should be performed in patients with suspected infection (i.e. with fever)
HbA1c can be used to get a picture of the blood sugar over the previous 3 months. This gives an idea of how long they have been diabetic prior to presenting.
Thyroid function tests and thyroid peroxidase antibodies (TPO) to test for associated autoimmune thyroid disease
Tissue transglutaminase (anti-TTG) antibodies for associated coeliac disease
Insulin antibodies, anti-GAD antibodies and islet cell antibodies to test for antibodies associated with destruction of the pancreas and the development of type 1 diabetes
Long term management of type 1 DM
Patient and family education is essential. Monitoring and treatment is relatively complex. The condition is life-long and requires the patient to fully understand and engage with their condition. Patients need to take responsibility for their diabetes and become “expert patients” as they mature and become independent from their family.
Management involves the following components:
Subcutaneous insulin regimes
Monitoring dietary carbohydrate intake
Monitoring blood sugar levels on waking, at each meal and before bed
Monitoring for and managing complications, both short and long term
Insulin
Insulin is usually prescribed as a combination of a background, long acting insulin given once a day, and a short acting insulin injected 30 minutes before the intake of carbohydrates (i.e. at meals). Alternatively, insulin can be administered by an insulin pump. Insulin regimes are initiated by a diabetic specialist.
Injecting into the same spot repeatedly can cause a condition called lipodystrophy, where the subcutaneous fat hardens and prevents normal absorption of insulin when further doses are injected into this area. 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.
Basal Bolus Regimes
Insulin regimes are initiated by a specialist in diabetes. Patients are usually initiated on a basal-bolus regime.
The basal part refers to an injection of a long acting insulin, such as “Lantus”, typically in the evening. This gives a constant background insulin throughout the day.
The bolus part refers to an injection of a short acting insulin, such as “Actrapid”, usually three times a day before meals. This is also injected according to the number of carbohydrates consumed every time the patient has a snack.
Insulin Pump
Insulin pumps are small devices that continuously infuse insulin at different rates to control blood sugar levels. They are an alternative to the basal bolus regimes. The pump pushes insulin through a small plastic tube (cannula) that is inserted under the skin. The cannula is replaced every 2 – 3 days and the insertion sites are rotated to prevent lipodystrophy and absorption issues.
To qualify for an insulin pump funded by the NHS the child needs to be over 12 and have difficulty controlling their HbA1c. Local criteria may vary.
The advantages of an insulin pump are better blood sugar control, more flexibility with eating and less injections. The disadvantages are difficulties learning to use the pump, having it attached at all times, blockages in the infusion set and a small risk of infection.
There are two types of insulin pump:
Tethered pump
Patch pump
Tethered pumps are devices with replaceable infusion sets and insulin. They are usually attached to the patients belt or around the waist with a tube that connects from the pump to the insertion site. The controls for the infusion are usually 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. Patch pumps are usually controlled by a separate remote.
Short term complications of type 1 DM
Short term complications relate to immediate insulin and blood glucose management:
Hypoglycaemia
Hyperglycaemia (and DKA)
Hypoglycaemia
Hypoglycaemia is a low blood sugar level. In diabetes this is caused by too much insulin, not enough carbohydrates or not processing the carbohydrates properly, for example in malabsorption, diarrhoea and vomiting and sepsis. Most patients are aware when they are hypoglycaemic by their symptoms, however some patients can be unaware until 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 with a combination of rapid acting glucose such as lucozade and slower acting carbohydrates such as biscuits or toast to maintain the blood sugar level when the rapid acting glucose is used up.
Options for treating severe hypoglycaemia where there is impairment of consciousness, seizures or coma, and oral glucose would not be safe, are IV dextrose and intramuscular glucagon. IM glucagon does not require a cannula. If a cannula is sited then 10% dextrose solution can be given according to local protocols, for example 2mg/kg bolus followed by a 5mg/kg/hour infusion.
Other causes of hypoglycaemia include hypothyroidism, glycogen storage disorders, growth hormone deficiency, liver cirrhosis, alcohol and fatty acid oxidation defects (such as MCADD).
Nocturnal hypoglycaemia is a common complication. The child may be sweaty overnight. Morning blood glucose levels may be raised. Diagnosis of nocturnal hypoglycaemia can be made by continuous glucose monitoring. It can be treated by altering the bolus insulin regimes and snacks at bedtime.
Hyperglycaemia
Patients that are hyperglycaemic, but not in DKA, may require their insulin dose to be increased. Patients will get to know their own individual response to insulin and be able to administer a dose to correct the hyperglycaemia. For example, they may learn that 1 unit of novorapid reduces their sugar level by around 4 mmol/l. Be conscious that it can take several hours to take effect and repeated doses could lead to hypoglycaemia. When they meet the criteria for DKA they need admission for inpatient management.
Long term complications of type 1 DM
Chronic exposure to hyperglycaemia causes damage to the endothelial cells of blood vessels. This leads to leaky, malfunctioning vessels that are unable to regenerate. High levels of sugar in the blood also causes suppression of the immune system, and creates an optimal environment for infectious organisms to thrive.
Macrovascular Complications
Coronary artery disease is a major cause of death in diabetics
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension
Microvascular Complications
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
Infection Related Complications
Urinary tract infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis
Monitoring type 1 DM
HbA1c
When we check HbA1c we are counting glycated haemoglobin, which is how much glucose is attached to the haemoglobin molecules inside red blood cells. This is considered to reflect the average blood glucose level over the last 3 months, because red blood cells have a lifespan of around 3 to 4 months. We measure it every 3 to 6 months to track the average blood sugar over time and determine how effective our interventions are and how well controlled the diabetes is. It requires a blood sample sent to the lab, usually red top EDTA bottle.
Capillary Blood Glucose
Capillary blood glucose is measured using a little machine called a glucose meter. It gives an immediate result. Patients with type 1 and type 2 diabetes rely on these machines to self-monitor their sugar levels.
Flash Glucose Monitoring (e.g. FreeStyle Libre)
This uses a sensor on the skin that measures the glucose level of the interstitial fluid in the subcutaneous tissue. There is a 5 minute lag behind blood glucose. The sensor records the glucose readings at short intervals so you get a really good impression of what the glucose levels are doing over time. The user needs to use a “reader” to swipe over the sensor. The reader shows the blood sugar readings. Sensors need replacing every 2 weeks for the FreeStyle Libre system. It is quite expensive and NHS funding is only available in certain areas at present. The 5 minute delay also means it is necessary to do capillary blood glucose (finger prick testing) checks if hypoglycaemia is suspected.
Ketogenesis
Ketogenesis normally occurs when there is an insufficient supply of glucose and glycogens stores are exhausted. This may happen during prolonged fasting or very low carbohydrate diets. 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 when under fasting conditions or on a very low carbohydrate, high fat diet. Ketone levels can be measured in the urine using a urine dipstick and in the blood using a ketone meter. People in ketosis have a characteristic acetone smell to their breath.
Ketone acids (ketones) are buffered in normal patients so the blood does not become acidotic. When underlying pathology (i.e. type 1 diabetes) causes extreme hyperglycaemic ketosis, this results in a metabolic acidosis that is life threatening. This is called diabetic ketoacidosis.
Pathophysiology of Diabetic Ketoacidosis (DKA)
Diabetic ketoacidosis occurs in type 1 diabetes, where the person is not producing adequate insulin themselves and is not injecting adequate insulin to compensate for this. It occurs when they body does not have enough insulin to use and process glucose. The main problems are ketoacidosis, dehydration and potassium imbalance.
Ketoacidosis
When the cells in the body have no fuel and think they are starving, they initiate the process of ketogenesis so they have a usable fuel. Over time the glucose and ketone levels get higher and higher. Initially the kidneys produce bicarbonate to buffer the ketone acids in the blood and maintain a normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become acidic. This is called ketoacidosis.
Dehydration
Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia.
Potassium Imbalance
Insulin normally drives potassium into cells. Without insulin, potassium is not added to and stored in cells. Serum potassium can be high or normal in diabetic ketoacidosis, as the kidneys continue to 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, and this can lead to fatal arrhythmias.
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to allow the cells to start taking up and using glucose and stop producing ketones.
Cerebral Oedema
Children with DKA are at high risk of developing cerebral oedema. Dehydration and high blood sugar 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. Rapid correction of dehydration and hyperglycaemia (with fluids and insulin) causes a rapid 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 (i.e. GCS) should be monitored very closely (e.g. hourly) to look for signs of cerebral oedema. Be concerned when patients being treated for diabetic ketoacidosis develop headaches, altered behaviour, bradycardia or changes to consciousness.
Management options for cerebral oedema are slowing IV fluids, IV mannitol and IV hypertonic saline. These should be guided by an experienced paediatrician.
Presentation of DKA
The patient will present with symptoms of the underlying hyperglycaemia, dehydration and acidosis:
Polyuria
Polydipsia
Nausea and vomiting
Weight loss
Acetone smell to their breath
Dehydration and subsequent hypotension
Altered consciousness
Symptoms of an underlying trigger (i.e. sepsis)
