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After reading this update feature you should be able to:
- Understand the insulin regimens used in the management of type 1 diabetes
- Discuss the time-action profiles of different insulines
- Explain how th initial total daily dose of insuling in adults is calculated.
Type 1 diabetes accounts for around 8 per cent of all patients with the disease and is caused by an absolute insulin deficiency due to destruction of the insulin producing beta cells in the pancreas. Both type 1 and type 2 diabetes result in hyperglycaemia.
Although type 1 and type 2 diabetes are differentiated conditions, they both share similar symptoms, including:
- Polyuria
- Polydipsia
- Extreme tiredness
- Unexplained weight loss
- Genital itching or thrush
- Cuts and wounds taking longer to heal
- Blurred vision.
However, the main symptoms of type 1 diabetes – polyuria, polydipsia, extreme tiredness and unexplained weight loss – occur very quickly and can be fatal if not managed. In comparison, symptoms develop more slowly in type 2 diabetes, allowing them to be missed, sometimes resulting in a delayed diagnosis.
Type 1 diabetes most commonly presents in children and young people but can also start in adults in the form of a slow-progressing autoimmune diabetes known as latent autoimmune diabetes in adults (LADA).
LADA can be easily mistaken for type 2 diabetes as the patient may not require insulin treatment for some years. If the patient has two or more of the following features, then the possibility of LADA should be considered:
- Age of onset <50 years
- Acute symptoms
- Body mass index less than 25kg/m²
- Personal or family history of autoimmune disease.
Management of type 1 diabetes
The use of insulin in type 1 diabetes is life-saving as it prevents the potentially life-threatening complication of diabetic ketoacidosis (DKA) by increasing glucose uptake to the adipose tissue and muscles. It also suppresses hepatic glucose release, therefore lowering blood glucose levels.
The long-term goal of insulin use is the prevention of diabetes-related complications, including microvascular complications (retinopathy, nephropathy and neuropathy) and macrovascular complications (cardiovascular disease, cerebrovascular disease and peripheral arterial disease).
There are three types of insulin available in the UK: human insulin, human insulin analogues and rarely used animal insulin. Insulins are categorised according to their time-action profiles: time to peak, onset of action and duration of action (see Table 1).
- Short acting, rapid acting and ultra-rapid acting insulins mimic the physiological secretion of insulin that occurs in response to the sharp rise of glucose following the ingestion of food or drink. These insulins are also known as prandial or bolus insulin.
- Intermediate, long acting and ultra-long acting insulins mimic the effect of basal insulin that is continuously released from the liver and is relatively constant but declines slightly during the night and peaks just before dawn. These insulins are also known as basal insulin.
All patients with type 1 diabetes should be offered a basal-bolus insulin regimen comprising multiple daily injections. The short or rapid acting insulin is injected before meals and basal insulin is injected once or twice daily, depending on the insulin. The first-line choice of basal insulin in type 1 diabetes is twice-daily insulin detemir.
However, an alternative option can be considered:
- If the patient is already on a different basal insulin and is meeting his or her agreed treatment goal
- If insulin detemir is not tolerated or the patient has a strong preference for once‑daily basal injections, then once-daily insulin glargine can be considered
- If there is a concern about nocturnal hypoglycaemia or patients need help from a carer or healthcare professional to administer injections, once-daily insulin degludec can be considered.
Rapid acting insulin analogues should be offered first-line to all patients with type 1 diabetes over rapid acting soluble human or animal insulins as bolus insulin.
Although newly diagnosed patients should not be offered insulin regimens other than a basal-bolus one, there may be circumstances where an alternative regimen, such as twice daily premixed, may be considered.
Overall, premixed insulins are not appropriate for patients with type 1 diabetes because the independent adjustment of the basal and bolus components are not possible. However, these insulins may be considered in those patients who simply prefer this simpler regimen. If this is the case, then a twice-daily premixed human insulin preparation is considered first-line.
The twice-daily premixed analogue insulins can be considered if the patient is having recurrent hypoglycaemia that is affecting their quality of life.
Some patients with type 1 diabetes manage their blood glucose levels with an insulin pump – a small electronic device that releases insulin at a regular rate throughout the day. This device is a treatment option for those aged ≥12 years whose attempts to achieve a HbA1c target with a basal-bolus regimen have resulted in hypoglycaemia with a significant impact on quality of life, or for those whose HbA1c levels remain high despite being motivated, on a basal-bolus regimen, carbohydrate counting (see later) and checking blood glucose levels ≥ four times daily.
These patients should only continue using a pump if it results in a sustained fall in HbA1c levels and/or a reduction in the frequency of hypoglycaemia episodes.
The pump uses short acting or rapid acting insulin and provides a basal rate of insulin and delivers mealtime bolus dosing. However, the patient must still measure blood glucose frequently in order to adjust the pump to deliver the appropriate amount of insulin. Therefore the use of an insulin pump requires access to trained healthcare professionals in pump therapy and a motivated patient to manage their diabetes.
Newer insulin pumps can link with continuous glucose monitoring (CGM) to further improve glycaemic control and quality of life for patients with type 1 diabetes. Such systems are called closed loop systems.
At diagnosis, the initial total daily dose of insulin in adults can be calculated as 0.2 to 0.4 units/kg/day. One half of the total daily dose of insulin calculated is given as basal insulin and the remaining half given as bolus insulin, which is further divided by three and that total given before meals.
It is important to note that patients with type 1 diabetes will experience a ‘honeymoon period’ just after diagnosis and may require fewer units of insulin as a result.
Once started on insulin, the patient should be introduced to the carbohydrate counting concept. This method is a more precise way to calculate doses of bolus insulin before meals. The patient counts the amount of carbohydrate their meal or snack contains and the dose of insulin is calculated based on the ratio of insulin to carbohydrate content.
For example, one unit of insulin lispro may be appropriate for every 15g of carbohydrate in a meal. This means that if a patient consumes 60g of carbohydrates for dinner, they would need to inject 4 units of insulin lispro. It is important to note the ratio is individualised and can be different at different times of the day.
This method allows more flexibility as the patient can calculate insulin doses for snacks (if the carbohydrate content is >10g) and prevents them from guessing how much insulin they need, stopping the injection of inappropriate doses. However, some patients may not understand this process and will monitor their blood glucose levels, adjusting insulin doses accordingly.
When a patient’s blood glucose levels are above target, extra insulin needs to be given. This is called the correction factor and depends on the average total daily dose of the insulin the patient is using. The correction factor is worked out by dividing 100 with the total daily dose of insulin. For example, if a patient is taking 50 units of insulin daily, then their correction factor is (100/50 units) = 2 units. This means that a single unit of bolus insulin will reduce their blood glucose levels by 2mmol/L.
The landmark Diabetes Control and Complications Trial (DCCT) showed that intensive glycaemic control in type 1 diabetes reduced the incidence of complications. Tight control was achieved by measuring blood glucose levels at least three times daily. Frequent self-monitoring of blood glucose levels is therefore key to maintaining good glycaemic control.
NICE recommends a HbA1c treatment target of 48mmol/mol or less. HbA1c or glycated haemoglobin depicts the average blood glucose levels of the previous three months. Patients with type 1 diabetes should aim for a fasting plasma glucose level of 5-7mmol/L on waking and blood glucose levels of 4-7mmol/L before meals at other times of the day.
Individualised HbA1c and blood glucose level targets should be agreed with each patient and factors such as daily activities, likelihood of complications, comorbidities, occupation and history of hypoglycaemia should be considered.
Real-time continuous glucose monitoring (rtCGM) or intermittently scanned continuous glucose monitoring (isCGM), commonly known as flash monitoring, provides 24/7 coverage and gives instantaneous real-time glucose levels, as well as rate of change of glucose levels, alerts and alarms for actual or impending hypoglycaemia and hyperglycaemia.
Generally, all patients with type 1 diabetes should be offered either rtCGM or isCGM flash devices. Even though patients with type 1 diabetes will be using CGM, they will still need to take capillary blood glucose measurements to check the accuracy of their CGM device, when their blood glucose levels are changing quickly, when their device stops working, or to confirm they are having hypoglycaemia.
| Table 1: Insulin types categorised according to their time-action profile | |||||
| Onset | Peak | Duration | Time of injection | Examples | |
| Short acting insulin | 30-60 minutes | 2-4 hours | Up to 8 hours | 20-30 minutes before meals |
Actrapid (human insulin) Humulin 5 (human insulin) |
| Rapid acting insulin | 10-20 minutes | 30-70 minutes | 2-5 hours | Just before, during, or after meals |
Admelog (insulin lispro) Apidra (insulin glulisine) Humalog (insulin lispro) NovoRapid (insulin aspart) Trurapi (insulin aspart) |
| Ultra-rapid acting insulin | 4 minutes | 40-60 minutes | 3-5 hours | Just before, during, or after meals |
Fiasp (insulin aspart) Lyumjev (insulin lispro) |
| Intermediate acting insulin (NPH insulin) | 2-4 hours | 4-8 hours | 14-16 hours | Once or twice daily |
Humulin I (human insulin) Insulatard (human insulin) |
| Long acting insulin | 0.5-2 hours | No peak | Up to 24 hours | Usually once daily. Insulin detemir is injected twice daily |
Abasaglar (insulin glargine) Lantus (insulin glargine) Levemir (insulin detemir) Semglee (insulin glargine) |
| Ultra-long acting insulin | 0.5-1.5 hours | No peak | Up to 42 hours | Once daily |
Tresiba (insulin degludec) Toujeo (insulin glargine) |
| Biphasic human insulin | 30-60 minutes | 2-8 hours | Up to 24 hours | Twice daily; 20-30 minutes before meals |
Humulin M3 Insuman Comb 25 and 50 |
| Biphasic analogue insulin | 15-20 minutes | 0.5-4 hours | 24 hours | Twice daily; just before, during or after meals |
Humalog Mix 25 and 30 NovoMix 30 |
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