Introduction to insulin
Insulin is the main hormone responsible for regulating blood glucose in the body. It is produced by the beta cells of the pancreatic Islets of Langerhans in response to blood glucose levels. People with type 1 diabetes are unable to produce insulin from their own beta cells, hence they require insulin injections to prevent hyperglycaemia and diabetic ketoacidosis. People with type 2 diabetes also have inadequate insulin production (despite an already elevated insulin level) to counteract insulin resistance in the peripheral tissues, leading to hyperglycaemia. Over time, people with type 2 diabetes will experience beta cell depletion, and will eventually become insulin-deficient as the disease progresses.
Physiologically, there are two patterns of insulin secretion from the beta cells. The first pattern is called the basal secretion, which is the continuous insulin secretion by the beta cell in response to the continuous glucose production from within the body, mainly by the liver. This basal insulin secretion occurs during rest, sleep, exercise, and other periods not associated with meals.
The second pattern of insulin secretion is called the prandial secretion, which is the insulin secretion in response to carbohydrate intake in meals. The prandial insulin secretion occurs in response to blood glucose in the portal system, which in turns received glucose directly from intestinal absorption of carbohydrates.
Once released, insulin will act on body cells to promote glucose uptake from the blood into the cells. Insulin will also inhibit glucagon secretion, which in turn reduces the glucose production by the liver and other organs.
Basal insulin
In people with type 1 diabetes and people with type 2 diabetes who continues to experience hyperglycaemia despite combination oral therapies, basal insulin treatment is used to help lower blood glucose throughout the day. The effect of basal insulin on blood glucose lowering is generally best seen on fasting blood glucose, with the exception of people who experience dawn phenomena or the Somogyi effect.
There are several types of basal insulin in the market. They are classified into intermediate-acting insulin (duration of action less than 24 hours) and long-acting insulin (duration of action 24 hours or more). Intermediate-acting insulin preparations includes NPH insulin and detemir (Levemir), whereas long-acting insulin preparations include glargine and degludec (Tresiba, not currently available in Malaysia). Glargine is also available in two different formulations, the standard U-100 formulation (Lantus) and the more concentrated U-300 formulation (Toujeo).
In general, basal insulin injections are administered at bedtime but occasionally intermediate-acting insulin may also be administered twice daily. Long-acting basal insulin are injected once daily in most situations. The adequacy of basal insulin dose is determined by the fasting blood glucose on the next day, and this is used to titrate basal insulin from the starting dose to the required dose for different individuals.
Prandial insulin
Prandial insulin, also known as mealtime insulin or bolus insulin, is administered at meal times to prevent hyperglycaemia that results from carbohydrate intake in meals. There are three types of prandial insulin; the regular human insulin, rapid-acting insulin (aspart, lispro, and glulisine), and ultra rapid-acting insulin (faster aspart and ultra-rapid lispro). Prandial insulins are administered before meals (20-30 minutes for regular insulin, 10-15 minutes for rapid-acting insulin, and less than 10 minutes for ultra rapid-acting insulin).
For people with type 2 diabetes, prandial insulin may be initially started on the largest meal, followed by the second and third meals of the day if HbA1c is still not within target. On the other hand, people with type 1 diabetes need to administer prandial insulin for every carbohydrate intake, and need to match the insulin dose to the amount of carbohydrate being ingested (carbohydrate counting is discussed in a separate section).
Occasionally, people with type 2 diabetes may use a mixed preparation with a fixed ratio of basal and prandial insulin (called premixed insulin) instead of injecting basal and prandial insulins separately.
Rapid-acting and ultra rapid-acting insulin preparations are also used with the insulin pump by people with type 1 diabetes to act as both basal and prandial insulins (insulin pump is discussed in a separate section).
Side effects of insulin
The most important side effect of insulin treatment is hypoglycaemia. The risk of hypoglycaemia is higher with more complex insulin treatment regimes, with the lowest risk seen in people treated with basal insulin alone, and the highest risk in people with multiple daily insulin treatment. All persons with diabetes who are treated with insulin and their caregivers must be able to recognize the symptoms of hypoglycaemia, have readily available glucometer devices to diagnose hypoglycaemia, and know how to treat hypoglycaemia. The risk of hypoglycaemia with insulin treatment can also be reduced with structured home blood glucose monitoring, using newer insulin preparations, as well as using continuous glucose monitoring (CGM) systems and/or insulin pumps, especially for people with type 1 diabetes (hypoglycaemia is discussed in a separate section).
The other side effect of insulin treatment is weight gain. Weight gain with insulin treatment is due to multiple factors, including water retention that occurs with normalization of blood glucose, recovery of muscle mass that was previously lost in people with uncontrolled diabetes, increased deposition of fat tissues due to the direct effect of insulin, and behavioural mechanisms to avoid hypoglycaemia which often includes over-eating. While weight gain may not be entirely avoidable with insulin treatment, it is important to ensure that over-dosing of insulin is avoided as this will create a cycle of hypoglycaemia, defensive over-eating, rebound hyperglycaemia, and further increase in insulin doses.
Monitoring insulin treatment and dose titration
In order to get the most out of insulin treatment, insulin doses need to be titrated to achieve the effective doses. Different person will need different doses of insulin, so there is no standard or universal dose of insulin for people with diabetes.
Insulin dose are titrated based on several outcomes, including home blood glucose readings, HbA1c, hypoglycaemia episodes, as well as time in range and time below range for CGM users. Basal insulin is titrated using the fasting blood glucose, typically in the morning, to achieve fasting blood glucose levels of less than 10 mmol/L. Prandial insulin is titrated using the post meal blood glucose, or blood glucose readings prior to the next meal. The target for post meal blood glucose is less than 10 mmol/L, while the target for blood glucose reading prior to the next meal is less than 7 mmol/L.
During clinic visits, both basal and prandial insulin doses will be further reviewed in accordance to HbA1c, hypoglycaemia episodes, and CGM parameters if available. Your doctor may further increase or decrease the insulin doses to tailor for your specific needs and risk profiles.