Type 1 diabetes is a condition where the pancreas stops being able to produce adequate insulin. Without insulin, the cells of the body cannot absorb glucose from the blood and use it as fuel. Therefore, the cells think there is no glucose available. Meanwhile, the glucose level in the blood keeps rising, causing hyperglycaemia.
The underlying cause of type 1 diabetes is unclear. There may be a genetic component, but it is not inherited in any clear pattern. Certain viruses, such as the Coxsackie B and enterovirus, may trigger it.
Type 1 diabetes may present with the classic triad of symptoms of hyperglycaemia:
- Polyuria (excessive urine)
- Polydipsia (excessive thirst)
- Weight loss (mainly through dehydration)
Alternatively, patients may present with diabetic ketoacidosis.
Eating carbohydrates causes a rise in blood glucose levels, as carbohydrates are absorbed from the small intestine into the blood. As the body uses these carbohydrates for energy, there is a fall in blood glucose levels. The body ideally wants to keep blood glucose concentration between 4.4 – 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 sugar 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 sugar levels and stress and works to increase blood sugar 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.
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, this results in a life-threatening metabolic acidosis. This is called diabetic ketoacidosis.
Pathophysiology of Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) occurs as a consequence of inadequate insulin. The most common scenarios for diabetic ketoacidosis to occur are:
- The initial presentation of type 1 diabetes
- An existing type 1 diabetic who is unwell for another reason, often with an infection
- An existing type 1 diabetic who is not adhering to their insulin regime
The three key features are:
- 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 to use as fuel. Over time, there are higher and higher glucose and ketones levels. 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 levels (hyperglycaemia) overwhelm the kidneys, and glucose leaks into the urine. The glucose in the urine draws water out by osmotic diuresis. This causes increased urine production (polyuria) and results in severe dehydration. Dehydration results in excessive thirst (polydipsia).
Insulin normally drives potassium into cells. Without insulin, potassium is not added to and stored in cells. The serum potassium can 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
The pathophysiology described above leads to:
- Metabolic acidosis (with a low bicarbonate)
- Potassium imbalance
Patients present with symptoms of these abnormalities:
- Nausea and vomiting
- Acetone smell to their breath
- Weight loss
- Hypotension (low blood pressure)
- Altered consciousness
Diabetic ketoacidosis may be triggered by an underlying condition, such as an infection. In any patient with DKA, it is also important to look for signs of infections and other underlying pathology that may need treatment.
Diagnosing Diabetic Ketoacidosis
Check the local DKA diagnostic criteria for your hospital. 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)
Treatment of Diabetic Ketoacidosis
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 dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones.
Diabetic ketoacidosis is a life-threatening medical emergency. Get experienced senior support and follow local protocols when treating patients. Local policies will dictate precisely what fluids and insulin to prescribe.
The principles of management can be remembered with the “FIG-PICK” mnemonic:
- F – Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
- I – Insulin – fixed rate insulin infusion (e.g., Actrapid at 0.1 units/kg/hour)
- G – Glucose – closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
- P – Potassium – add potassium to IV fluids and monitor closely (e.g., every hour initially)
- I – Infection – treat underlying triggers such as infection
- C – Chart fluid balance
- K – Ketones – monitor blood ketones, pH and bicarbonate
Before stopping the insulin and fluid infusions:
- Ketosis and acidosis should have resolved
- They should be eating and drinking
- They should have started their regular subcutaneous insulin
The key complications during the treatment are:
- Hypoglycaemia (low blood sugar)
- Hypokalaemia (low potassium)
- Cerebral oedema, particularly in children
- Pulmonary oedema secondary to fluid overload or acute respiratory distress syndrome
TOM TIP: Remember, under normal circumstances, the rate of potassium infusion should not exceed 10 mmol/hour, as there is a risk of inducing an arrhythmia or cardiac arrest. In DKA, rates up to 20 mmol/hour may be used. Higher rates are only used in specific scenarios under expert supervision with cardiac monitoring and through a central line (rather than a peripheral cannula).
Autoantibodies and Serum C-Peptide
Checking for autoantibodies and serum C-peptide is not routinely recommended. They can be helpful when there is doubt about whether a patient has type 1 or type 2 diabetes.
Autoantibodies in type 1 diabetes are:
- Anti-islet cell antibodies
- Anti-GAD antibodies
- Anti-insulin antibodies
Serum C‑peptide is a measure of insulin production. It is low with low insulin production and high with high insulin production.
Monitoring and treatment are relatively complex, therefore patient education is essential. Type 1 diabetes is life-long and requires the patient to understand and engage with their condition fully. It involves the following components:
- Subcutaneous insulin
- Monitoring dietary carbohydrate intake
- Monitoring blood sugar levels upon waking, at each meal and before bed
- Monitoring for and managing complications, both short and long term
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 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 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
- 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.
A pancreas transplant involves implanting a donor pancreas to produce insulin. The original pancreas is left in place to continue producing digestive enzymes. The procedure carries significant risks, and life-long immunosuppression is required to prevent rejection. Therefore, it is reserved for patients with severe hypoglycaemic episodes and those also having kidney transplants.
Islet transplantation involves inserting donor islet cells into the patient’s liver. These islet cells produce insulin and help in managing diabetes. However, patients often still need insulin therapy after islet transplantation.
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). It is measured every 3 to 6 months to track the average sugar levels. It is a lab test.
Capillary blood glucose (finger-prick test) can be measured using a blood glucose monitor, giving an immediate result. Patients with type 1 and type 2 diabetes rely on these machines for self-monitoring their sugar levels.
Flash glucose monitors (e.g., FreeStyle Libre 2) use 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 an excellent impression of what the glucose levels are doing over time. The user needs to use their mobile phone to swipe over the sensor and collect the reading. Sensors need replacing every 2 weeks for the FreeStyle Libre system. The 5-minute delay means it is necessary to do capillary blood glucose testing if hypoglycaemia is suspected.
Continuous glucose monitors (CGM) are similar the flash glucose monitors in that a sensor on the skin monitors the sugar level in the interstitial fluid. However, continuous glucose monitors send the readings over bluetooth and do not require the patient to scan the sensor.
A closed-loop system, also called an artificial pancreas, involves a combination of a continuous glucose monitor and an insulin pump. The devices communicate to automatically adjust the insulin based on the glucose readings. Patients still need to input their carbohydrate intake and adjust the system to account for strenuous exercise.
Short-term complications relate to immediate insulin and blood glucose management:
- Hyperglycaemia (and diabetic ketoacidosis)
Hypoglycaemia is a low blood sugar level. This may be caused by too much insulin, not consuming enough carbohydrates or not processing the carbohydrates correctly, for example, 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., 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 sugar 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 ketones). Patients meeting the criteria for DKA need admission for inpatient management.
Long Term Complications
Chronic high blood glucose levels cause damage to the endothelial cells of blood vessels. This leads to leaky, malfunctioning vessels that are unable to regenerate. High glucose levels also cause immune system dysfunction and create an optimal environment for infectious organisms to thrive.
Macrovascular complications include:
- Coronary artery disease is a significant cause of death in diabetics
- Peripheral ischaemia causes poor skin healing and diabetic foot ulcers
Microvascular complications include:
- Peripheral neuropathy
- Kidney disease, particularly glomerulosclerosis
Infection-related complications include:
- Urinary tract infections
- Skin and soft tissue infections, particularly in the feet
- Fungal infections, particularly oral and vaginal candidiasis
Last updated March 2023